Peer Reviewed Publications
2021 |
Bulterys, Michelle A; Sharma, Monisha ; Mugwanya, Kenneth ; Stein, Gabrielle ; Mujugira, Andrew ; Nakyanzi, Agnes ; Twohey-Jacobs, Lorraine ; Ware, Norma C; Heffron, Renee ; Celum, Connie Correlates of HIV Status Nondisclosure by Pregnant Women Living With HIV to Their Male Partners in Uganda: A Cross-Sectional Study Journal Article JAIDS Journal of Acquired Immune Deficiency Syndromes:, 86 (4), pp. 389-395, 2021. @article{Bulterys2021, title = {Correlates of HIV Status Nondisclosure by Pregnant Women Living With HIV to Their Male Partners in Uganda: A Cross-Sectional Study}, author = {Bulterys, Michelle A. and Sharma, Monisha and Mugwanya, Kenneth and Stein, Gabrielle and Mujugira, Andrew and Nakyanzi, Agnes and Twohey-Jacobs, Lorraine and Ware, Norma C. and Heffron, Renee and Celum, Connie}, url = {https://journals.lww.com/jaids/Abstract/2021/04010/Correlates_of_HIV_Status_Nondisclosure_by_Pregnant.1.aspx?context=LatestArticles }, doi = { doi: 10.1097/QAI.0000000000002566}, year = {2021}, date = {2021-04-21}, journal = {JAIDS Journal of Acquired Immune Deficiency Syndromes:}, volume = {86}, number = {4}, pages = {389-395}, abstract = {Abstract Background: HIV status disclosure by pregnant women living with HIV (PWLHIV) to their male partners is associated with improved maternal and infant outcomes. Understanding relationship factors associated with nondisclosure of HIV status by PWLHIV to their partners can inform the design of interventions to facilitate disclosure. Methods: We conducted a cross-sectional study using enrollment data from 500 PWLHIV unaware of their male partners' HIV status and participating in a randomized clinical trial assessing secondary distribution of HIV self-testing kits in Kampala, Uganda. The primary outcome was women's HIV status nondisclosure to their partners. We conducted univariate and multivariate binomial regressions to assess the association between baseline sociodemographic, HIV history, and relationship characteristics with HIV status nondisclosure. Results: 68.2% of the 500 PWLHIV had not disclosed their HIV status to their partner(s). Factors associated with higher likelihood of nondisclosure included relationship duration <1 year [adjusted prevalence ratio (aPR = 1.25); 95% confidence interval (CI): 1.02 to 1.54], being in a polygamous relationship (aPR = 1.21; 95% CI: 1.07 to 1.36), unmarried (aPR = 1.20; 95% CI: 1.07 to 1.35), uncertainty about whether their partner had ever tested for HIV (aPR = 1.55; 95% CI: 1.28 to 1.88), and a lack of social support from people aware of their status (aPR = 1.32; 95% CI: 1.18 to 1.49). Conclusion: Relationship factors, including shorter-term, unmarried, and polygamous relationships and uncertainty about partner's HIV testing history, were associated with higher likelihood of pregnant women's nondisclosure of HIV status to their partner. Interventions that facilitate couples' HIV testing and disclosure, provide counseling to reduce relationship dissolution in serodiscordant couples, and offer peer support for women may increase disclosure. ClinicaltrialsRegistration: Clinicaltrials.gov ID number: NCT03484533.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: HIV status disclosure by pregnant women living with HIV (PWLHIV) to their male partners is associated with improved maternal and infant outcomes. Understanding relationship factors associated with nondisclosure of HIV status by PWLHIV to their partners can inform the design of interventions to facilitate disclosure. Methods: We conducted a cross-sectional study using enrollment data from 500 PWLHIV unaware of their male partners' HIV status and participating in a randomized clinical trial assessing secondary distribution of HIV self-testing kits in Kampala, Uganda. The primary outcome was women's HIV status nondisclosure to their partners. We conducted univariate and multivariate binomial regressions to assess the association between baseline sociodemographic, HIV history, and relationship characteristics with HIV status nondisclosure. Results: 68.2% of the 500 PWLHIV had not disclosed their HIV status to their partner(s). Factors associated with higher likelihood of nondisclosure included relationship duration <1 year [adjusted prevalence ratio (aPR = 1.25); 95% confidence interval (CI): 1.02 to 1.54], being in a polygamous relationship (aPR = 1.21; 95% CI: 1.07 to 1.36), unmarried (aPR = 1.20; 95% CI: 1.07 to 1.35), uncertainty about whether their partner had ever tested for HIV (aPR = 1.55; 95% CI: 1.28 to 1.88), and a lack of social support from people aware of their status (aPR = 1.32; 95% CI: 1.18 to 1.49). Conclusion: Relationship factors, including shorter-term, unmarried, and polygamous relationships and uncertainty about partner's HIV testing history, were associated with higher likelihood of pregnant women's nondisclosure of HIV status to their partner. Interventions that facilitate couples' HIV testing and disclosure, provide counseling to reduce relationship dissolution in serodiscordant couples, and offer peer support for women may increase disclosure. ClinicaltrialsRegistration: Clinicaltrials.gov ID number: NCT03484533. |
2020 |
Mpoza, Edward; Rajasingham, Radha; Tugume, Lillian; Rhein, Joshua; Nabaggala, Maria Sarah; Ssewanyana, Isaac; Nyegenye, Wilson; Kushemererwa, Grace Esther; Kalamya, Vivienne Mulema Julius; Kiyaga, Charles; Kabanda, Joseph; Ssali, Mina; Boulware, David R; Meya, David B Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure Journal Article Clinical Infectious Diseases, 71 (7), pp. 1726–1731, 2020. @article{Mpoza2020, title = {Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure }, author = { Edward Mpoza and Radha Rajasingham and Lillian Tugume and Joshua Rhein and Maria Sarah Nabaggala and Isaac Ssewanyana and Wilson Nyegenye and Grace Esther Kushemererwa and Vivienne Mulema Julius Kalamya and Charles Kiyaga and Joseph Kabanda and Mina Ssali and David R Boulware and David B Meya}, url = {https://academic.oup.com/cid/article/71/7/1726/5611261?login=true}, doi = {https://doi.org/10.1093/cid/ciz1069}, year = {2020}, date = {2020-11-03}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {7}, pages = {1726–1731}, abstract = {Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. Conclusions In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL. cryptococcal antigenemia, virologic failure, ART experienced, HIV Topic: hiv meningitis cryptococcal meningitis cd4 count determination procedure plasma uganda viral load result cryptococcus anti-retroviral agents cryptococcal polysaccharide test virologic failure }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. Conclusions In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL. cryptococcal antigenemia, virologic failure, ART experienced, HIV Topic: hiv meningitis cryptococcal meningitis cd4 count determination procedure plasma uganda viral load result cryptococcus anti-retroviral agents cryptococcal polysaccharide test virologic failure |
Laker, Eva Agnes Odongpiny; Arinaitwe, Arnold; Owarwo, Noela; Onzia, Annet; Nasasira, Benson; Wailagala, Abdullah; Kalule, Ivan; Anguzu, Godwin; Kiragga, Agnes; Seden, Kay; Lwanga, Isaac; Castelnuovo, Barbara; Musomba, Rachel; Lamorde, Mohammed Drug Safety , 43 , pp. 1133–1140, 2020. @article{Laker2020, title = {The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women}, author = {Eva Agnes Odongpiny Laker and Arnold Arinaitwe and Noela Owarwo and Annet Onzia and Benson Nasasira and Abdullah Wailagala and Ivan Kalule and Godwin Anguzu and Agnes Kiragga and Kay Seden and Isaac Lwanga and Barbara Castelnuovo and Rachel Musomba and Mohammed Lamorde }, url = {https://link.springer.com/article/10.1007/s40264-020-00974-9}, doi = {https://doi.org/10.1007/s40264-020-00974-9}, year = {2020}, date = {2020-11-01}, journal = {Drug Safety }, volume = {43}, pages = {1133–1140}, abstract = {Abstract Introduction and Objective In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women’s choices to switch off dolutegravir. Methods A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. Results Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30–42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. Conclusions A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Introduction and Objective In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women’s choices to switch off dolutegravir. Methods A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. Results Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30–42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. Conclusions A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low. |
Kwizera, Richard; Bongomin, Felix; Lukande, Robert Deep fungal infections diagnosed by histology in Uganda: a 70-year retrospective study Journal Article Medical Mycology, 58 (8), pp. 1044–1052, 2020. @article{Kwizera2020b, title = {Deep fungal infections diagnosed by histology in Uganda: a 70-year retrospective study}, author = { Richard Kwizera and Felix Bongomin and Robert Lukande}, url = {https://academic.oup.com/mmy/article-abstract/58/8/1044/5815443}, doi = { https://doi.org/10.1093/mmy/myaa018}, year = {2020}, date = {2020-11-01}, journal = {Medical Mycology}, volume = {58}, number = {8}, pages = {1044–1052}, abstract = {Abstract Fungal infections cause substantial morbidity and mortality. However, the burden of deep fungal infections is not well described in Uganda. We aimed to estimate the burden and etiology of histologically diagnosed deep fungal infections in Uganda. We retrospectively reviewed histology reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 to identify any reports that had a fungal infection as the diagnosis. Over the study period, 697 cases of deep fungal infections were identified with an average incidence of 0.73/100,000 persons per decade. There was a general decline in the number of cases detected. Median age of the cases was 28 years (IQR: 11–40) and majority (59%) were male. The age group of 0–10 years were the most affected. The foot was the most affected part of the body (26%). Deep mycoses identified include eumycetoma (32%), subcutaneous phycomycosis (26%), histoplasmosis (9.2%), chromoblastomycosis (4.6%), aspergillosis (3.3%), cryptococcosis (3.3%), blastomycosis (1.6%), subcutaneous mycosis (1.4%), dermatomycosis (1.3%), coccidioidomycosis (0.6%), mucormycosis (0.6%), and sporotrichosis (0.1%). Histoplasma was the commonest causative agent (9.2%) followed by Aspergillus (3.4%) and Cryptococcus (3.3%), while 81% of the fungal pathogens were not identified to genus/species level. Only 31% of the cases were diagnosed clinically as deep fungal infections. There is a substantial burden of deep fungal infections caused by multiple fungal pathogens in Uganda. There is need to build local capacity for mycology so as to improve on the index of clinical suspicion and diagnostic capabilities. deep mycoses, histology, opportunistic mycoses, endemic mycoses, Uganda Topic: mycoses uganda histology mycosis, deep }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Fungal infections cause substantial morbidity and mortality. However, the burden of deep fungal infections is not well described in Uganda. We aimed to estimate the burden and etiology of histologically diagnosed deep fungal infections in Uganda. We retrospectively reviewed histology reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 to identify any reports that had a fungal infection as the diagnosis. Over the study period, 697 cases of deep fungal infections were identified with an average incidence of 0.73/100,000 persons per decade. There was a general decline in the number of cases detected. Median age of the cases was 28 years (IQR: 11–40) and majority (59%) were male. The age group of 0–10 years were the most affected. The foot was the most affected part of the body (26%). Deep mycoses identified include eumycetoma (32%), subcutaneous phycomycosis (26%), histoplasmosis (9.2%), chromoblastomycosis (4.6%), aspergillosis (3.3%), cryptococcosis (3.3%), blastomycosis (1.6%), subcutaneous mycosis (1.4%), dermatomycosis (1.3%), coccidioidomycosis (0.6%), mucormycosis (0.6%), and sporotrichosis (0.1%). Histoplasma was the commonest causative agent (9.2%) followed by Aspergillus (3.4%) and Cryptococcus (3.3%), while 81% of the fungal pathogens were not identified to genus/species level. Only 31% of the cases were diagnosed clinically as deep fungal infections. There is a substantial burden of deep fungal infections caused by multiple fungal pathogens in Uganda. There is need to build local capacity for mycology so as to improve on the index of clinical suspicion and diagnostic capabilities. deep mycoses, histology, opportunistic mycoses, endemic mycoses, Uganda Topic: mycoses uganda histology mycosis, deep |
Nasuuna, Esther; Tenforde, Mark W; Muganzi, Alex; Jarvis, Joseph N; Manabe, Yukari C; Kigozi, Joanita Reduction in Baseline CD4 Count Testing Following Human Immunodeficiency Virus “Treat All” Adoption in Uganda Journal Article Clinical Infectious Diseases, 71 (9), pp. 2497–2499, 2020. @article{Nasuuna2020, title = {Reduction in Baseline CD4 Count Testing Following Human Immunodeficiency Virus “Treat All” Adoption in Uganda }, author = {Esther Nasuuna and Mark W Tenforde and Alex Muganzi and Joseph N Jarvis and Yukari C Manabe and Joanita Kigozi}, url = {https://academic.oup.com/cid/article-abstract/71/9/2497/5830931}, doi = {https://doi.org/10.1093/cid/ciaa261}, year = {2020}, date = {2020-11-01}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {9}, pages = {2497–2499}, abstract = {Abstract Baseline CD4 testing rates declined from 73% to 21% between 2013 and 2018 with adoption of “Treat All” in Uganda. Advanced human immunodeficiency virus (HIV) disease (CD4 count < 200 cells/µL) remained common (24% of those tested in 2018, 83% of whom had World Health Organization stage I/II disease). Despite frequent presentation with advanced HIV disease, CD4 testing has declined dramatically. HIV, CD4, opportunistic infections, treat all, test-and-treat}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Baseline CD4 testing rates declined from 73% to 21% between 2013 and 2018 with adoption of “Treat All” in Uganda. Advanced human immunodeficiency virus (HIV) disease (CD4 count < 200 cells/µL) remained common (24% of those tested in 2018, 83% of whom had World Health Organization stage I/II disease). Despite frequent presentation with advanced HIV disease, CD4 testing has declined dramatically. HIV, CD4, opportunistic infections, treat all, test-and-treat |
Boulware, David R; Nalintya, Elizabeth; Rajasingham, Radha; Kirumira, Paul; Naluyima, Rose; Turya, Fred; Namanda, Sylvia; Rutakingirwa, Morris K; Skipper, Caleb P; Nikweri, Yofesi; Hullsiek, Kathy Huppler; Bangdiwala, Ananta S; Meya, David B Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial Journal Article Medical Mycology, 58 (8), pp. 1037–1043, 2020. @article{Boulware2020, title = {Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial }, author = {David R Boulware and Elizabeth Nalintya and Radha Rajasingham and Paul Kirumira and Rose Naluyima and Fred Turya and Sylvia Namanda and Morris K Rutakingirwa and Caleb P Skipper and Yofesi Nikweri and Kathy Huppler Hullsiek and Ananta S Bangdiwala and David B Meya}, url = {https://academic.oup.com/mmy/article-abstract/58/8/1037/5838059}, doi = { https://doi.org/10.1093/mmy/myaa033}, year = {2020}, date = {2020-11-01}, journal = {Medical Mycology}, volume = {58}, number = {8}, pages = {1037–1043}, abstract = {Abstract Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800 mg for 2 weeks, then 400 mg for 10 weeks, then 200 mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100 mg/day doses up to 400 mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n = 4 sertraline group; n = 3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200 mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia. cryptococcosis, cryptococcal meningitis, preemptive therapy, sertraline, clinical trial Topic: meningitis fluconazole psychotic disorders sertraline cryptococcus }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800 mg for 2 weeks, then 400 mg for 10 weeks, then 200 mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100 mg/day doses up to 400 mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n = 4 sertraline group; n = 3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200 mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia. cryptococcosis, cryptococcal meningitis, preemptive therapy, sertraline, clinical trial Topic: meningitis fluconazole psychotic disorders sertraline cryptococcus |
Kiggundu, Thomas; Kalyesubula, Robert; Andia-Biraro, Irene; Makanga, Gyaviira; Byakika-Kibwika, Pauline BMC Nephrology, 21 (1), pp. 440, 2020. @article{Kiggundu2020, title = {Prevalence of microalbuminuria and associated factors among HIV − infected ART naïve patients at Mulago hospital: a cross-sectional study in Uganda}, author = {Thomas Kiggundu and Robert Kalyesubula and Irene Andia-Biraro and Gyaviira Makanga and Pauline Byakika-Kibwika }, url = {https://link.springer.com/article/10.1186/s12882-020-02091-2}, doi = {https://doi.org/10.1186/s12882-020-02091-2}, year = {2020}, date = {2020-10-20}, journal = {BMC Nephrology}, volume = {21}, number = {1}, pages = {440}, abstract = {Abstract Background HIV infection affects multiple organs and the kidney is a common target making renal disease, one of the recognized complications. Microalbuminuria represents an early, important marker of kidney damage in several populations including HIV-infected antiretroviral therapy (ART) naïve patients. Early detection of microalbuminuria is critical to slowing down progression to chronic kidney disease (CKD) in HIV-infected patients, however, the burden of microalbuminuria in HIV-infected antiretroviral therapy (ART) naïve patients in Uganda is unclear. Methods A cross-sectional study was conducted in the Mulago Immune suppression syndrome (ISS) clinic among adult HIV − infected ART naïve outpatients. Data on patient demographics, medical history was collected. Physical examination was performed to assess body mass index (BMI) and hypertension. A single spot morning urine sample from each participant was analysed for microalbuminuria using spectrophotometry and colorimetry. Microalbuminuria was defined by a urine albumin creatinine ratio (UACR) 30-299 mg/g and macroalbuminuria by a UACR > 300 mg/g. To assess the factors associated with microalbuminuria, chi-square, Fisher’s exact test, quantile regression and logistic regression were used. Results A total of 185 adult participants were consecutively enrolled with median age and CD4+ counts of 33(IQR = 28–40) years and 428 (IQR = 145–689) cells/μL respectively. The prevalence of microalbuminuria was 18.9% (95% CI, 14–25%). None of the participants had macroalbuminuria. CD4+ count <350cells/μL was associated with increased risk of microalbuminuria (OR: 0.27, 95% CI: 0.12–0.59), P value = 0.001). Diabetes mellitus, hypertension, smoking, alcohol intake were not found to be significantly associated with microalbuminuria. Conclusion Microalbuminuria was highly prevalent in adult HIV − infected ART naive patients especially those with low CD4+ count. There is need to study the effect of ART on microalbuminuria in adult HIV − infected patients.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background HIV infection affects multiple organs and the kidney is a common target making renal disease, one of the recognized complications. Microalbuminuria represents an early, important marker of kidney damage in several populations including HIV-infected antiretroviral therapy (ART) naïve patients. Early detection of microalbuminuria is critical to slowing down progression to chronic kidney disease (CKD) in HIV-infected patients, however, the burden of microalbuminuria in HIV-infected antiretroviral therapy (ART) naïve patients in Uganda is unclear. Methods A cross-sectional study was conducted in the Mulago Immune suppression syndrome (ISS) clinic among adult HIV − infected ART naïve outpatients. Data on patient demographics, medical history was collected. Physical examination was performed to assess body mass index (BMI) and hypertension. A single spot morning urine sample from each participant was analysed for microalbuminuria using spectrophotometry and colorimetry. Microalbuminuria was defined by a urine albumin creatinine ratio (UACR) 30-299 mg/g and macroalbuminuria by a UACR > 300 mg/g. To assess the factors associated with microalbuminuria, chi-square, Fisher’s exact test, quantile regression and logistic regression were used. Results A total of 185 adult participants were consecutively enrolled with median age and CD4+ counts of 33(IQR = 28–40) years and 428 (IQR = 145–689) cells/μL respectively. The prevalence of microalbuminuria was 18.9% (95% CI, 14–25%). None of the participants had macroalbuminuria. CD4+ count <350cells/μL was associated with increased risk of microalbuminuria (OR: 0.27, 95% CI: 0.12–0.59), P value = 0.001). Diabetes mellitus, hypertension, smoking, alcohol intake were not found to be significantly associated with microalbuminuria. Conclusion Microalbuminuria was highly prevalent in adult HIV − infected ART naive patients especially those with low CD4+ count. There is need to study the effect of ART on microalbuminuria in adult HIV − infected patients. |
Kakooza, Francis; Musinguzi, Patrick; Workneh, Meklit; Walwema, Richard; Kyambadde, Peter; Mande, Emmanuel; Lubega, Christopher; Nakasi, Jhamira M; Kiggundu, Reuben; and Hamill, Matthew M; Bagaya, Bernard S; Lamorde, Mohammed; Unemo, Magnus; Manabe, Yukari C Sexually Transmitted Infections, 2020. @article{Kakooza2020, title = {Implementation of a standardised and quality-assured enhanced gonococcal antimicrobial surveillance programme in accordance with WHO protocols in Kampala, Uganda}, author = {Francis Kakooza and Patrick Musinguzi and Meklit Workneh and Richard Walwema and Peter Kyambadde and Emmanuel Mande and Christopher Lubega and Jhamira M Nakasi and Reuben Kiggundu and and Matthew M Hamill and Bernard S Bagaya and Mohammed Lamorde and Magnus Unemo and Yukari C Manabe}, url = {https://sti.bmj.com/content/early/2020/10/19/sextrans-2020-054581.abstract}, doi = {http://dx.doi.org/10.1136/sextrans-2020-054581}, year = {2020}, date = {2020-10-20}, journal = {Sexually Transmitted Infections}, abstract = {Abstract Objectives The emergence of multidrug-resistant Neisseria gonorrhoeae (NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda. Methods From March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed. Results Of the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime. Conclusions We established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Objectives The emergence of multidrug-resistant Neisseria gonorrhoeae (NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda. Methods From March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed. Results Of the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime. Conclusions We established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions. |
Muwonge, Timothy R; Nsubuga, Rogers; Brown, Charles; Nakyanzi, Agnes; Bagaya, Monica; Bambia, Felix; Katabira, Elly; Kyambadde, Peter; Baeten, Jared M; Heffron, Renee; Celum, Connie; Mujugira, Andrew; Haberer, Jessica E Knowledge and barriers of PrEP delivery among diverse groups of potential PrEP users in Central Uganda Journal Article PLOS ONE, 15 (10), pp. e0241399, 2020. @article{Muwonge2020, title = {Knowledge and barriers of PrEP delivery among diverse groups of potential PrEP users in Central Uganda}, author = {Timothy R. Muwonge and Rogers Nsubuga and Charles Brown and Agnes Nakyanzi and Monica Bagaya and Felix Bambia and Elly Katabira and Peter Kyambadde and Jared M. Baeten and Renee Heffron and Connie Celum and Andrew Mujugira and Jessica E. Haberer}, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241399}, doi = { https://doi.org/10.1371/journal.pone.0241399}, year = {2020}, date = {2020-10-15}, journal = {PLOS ONE}, volume = {15}, number = {10}, pages = {e0241399}, abstract = {Abstract Background Scale-up of oral pre-exposure prophylaxis (PrEP) for HIV prevention in Uganda began with serodiscordant couples (SDC) and has expanded to other most at-risk populations (MARPs). We explored knowledge, acceptability, barriers and facilitators of PrEP use among potential PrEP users in four MARPs (SDC; men who have sex with men [MSM]; female sex workers [FSW], and fisher folk). Methods We administered quantitative surveys to potential PrEP users in multiple settings in Central Uganda at baseline and approximately 9 months after healthcare worker (HCW) training on PrEP. Results The survey was completed by 250 potential PrEP users at baseline and 125 after HCW training; 55 completed both surveys. For these 250 participants, mean age was 28.5 years (SD 6.9), 47% were male and 6% were transgender women, with approximately even distribution across MARPs and recruitment locations (urban, peri-urban, and rural). Most (65%) had not heard about PrEP. After HCW training, 24% of those sampled were aware of PrEP, and the proportion of those who accurately described PrEP as “antiretrovirals to be used before HIV exposure” increased from 54% in the baseline survey to 74% in the second survey (p<0.001). The proportion of participants who reported HCW as a source of PrEP information increased after training (59% vs 91%, p<0.001). In both surveys, nearly all participants indicated they were willing to take PrEP if offered. The most common anticipated barriers to PrEP were stigma, transportation, accessibility, busy schedules, and forgetfulness. Closeness to home was a common facilitator for all participant categories. Conclusions Initial awareness of PrEP was low, but PrEP knowledge and interest increased among diverse MARPs after HCW training. Demand creation and HCW training will be critical for increasing PrEP awareness among key populations, with support to overcome barriers to PrEP use. These findings should encourage the acceleration of PrEP rollout in Uganda.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Scale-up of oral pre-exposure prophylaxis (PrEP) for HIV prevention in Uganda began with serodiscordant couples (SDC) and has expanded to other most at-risk populations (MARPs). We explored knowledge, acceptability, barriers and facilitators of PrEP use among potential PrEP users in four MARPs (SDC; men who have sex with men [MSM]; female sex workers [FSW], and fisher folk). Methods We administered quantitative surveys to potential PrEP users in multiple settings in Central Uganda at baseline and approximately 9 months after healthcare worker (HCW) training on PrEP. Results The survey was completed by 250 potential PrEP users at baseline and 125 after HCW training; 55 completed both surveys. For these 250 participants, mean age was 28.5 years (SD 6.9), 47% were male and 6% were transgender women, with approximately even distribution across MARPs and recruitment locations (urban, peri-urban, and rural). Most (65%) had not heard about PrEP. After HCW training, 24% of those sampled were aware of PrEP, and the proportion of those who accurately described PrEP as “antiretrovirals to be used before HIV exposure” increased from 54% in the baseline survey to 74% in the second survey (p<0.001). The proportion of participants who reported HCW as a source of PrEP information increased after training (59% vs 91%, p<0.001). In both surveys, nearly all participants indicated they were willing to take PrEP if offered. The most common anticipated barriers to PrEP were stigma, transportation, accessibility, busy schedules, and forgetfulness. Closeness to home was a common facilitator for all participant categories. Conclusions Initial awareness of PrEP was low, but PrEP knowledge and interest increased among diverse MARPs after HCW training. Demand creation and HCW training will be critical for increasing PrEP awareness among key populations, with support to overcome barriers to PrEP use. These findings should encourage the acceleration of PrEP rollout in Uganda. |
Donovan, Joseph; Cresswell, Fiona V; Thuong, Nguyen Thuy Thuong; Boulware, David R; Thwaites, Guy E; Bahr, Nathan C; Consortium, Tuberculous Meningitis International Research Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward Journal Article Clinical Infectious Diseases, 71 (8), pp. 2002–2005, 2020. @article{Donovan2020, title = {Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward }, author = { Joseph Donovan and Fiona V Cresswell and Nguyen Thuy Thuong Thuong and David R Boulware and Guy E Thwaites and Nathan C Bahr and Tuberculous Meningitis International Research Consortium }, url = {https://academic.oup.com/cid/article/71/8/2002/5858077?login=true}, doi = {https://doi.org/10.1093/cid/ciaa473}, year = {2020}, date = {2020-10-15}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {8}, pages = {2002–2005}, abstract = {Abstract The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM. Keywords tuberculous meningitis, diagnosis, Ultra, Xpert, cerebrospinal fluid}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM. Keywords tuberculous meningitis, diagnosis, Ultra, Xpert, cerebrospinal fluid |
Manabe, Yukari C; Reuland, Carolyn; Yu, Tong; Azamfirei, Razvan; Church, Taylor; Brown, Diane M; Sewell, Thelio T; Hardick, Justin P; Blair, Paul W; Heaney, Chris D; Pekosz, View ORCID ProfileAndrew; Thomas, David L Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection Journal Article MedRxiv, 2020, (This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.). @article{Manabe2020c, title = {Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection}, author = {Yukari C. Manabe and Carolyn Reuland and Tong Yu and Razvan Azamfirei and Taylor Church and Diane M. Brown and Thelio T. Sewell and Justin P. Hardick and Paul W. Blair and Chris D. Heaney and View ORCID ProfileAndrew Pekosz and David L. Thomas}, url = {https://www.medrxiv.org/content/10.1101/2020.10.07.20208520v1}, doi = {https://doi.org/10.1101/2020.10.07.20208520 }, year = {2020}, date = {2020-10-12}, journal = {MedRxiv}, abstract = {Abstract In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.}, note = {This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others. |
Manabe, Yukari C; Reuland, Carolyn; Yu, Tong; Azamfirei, Razvan; Church, Taylor; Brown, Diane M; Sewell, Thelio T; Hardick, Justin P; Blair, Paul W; Heaney, Chris D; Andrew Pekosz, David Thomas L Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection Journal Article medRxiv - The Preprint Server for Health Sciences, 2020, (This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.). @article{Manabe2020b, title = {Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection}, author = {Yukari C. Manabe and Carolyn Reuland and Tong Yu and Razvan Azamfirei and Taylor Church and Diane M. Brown and Thelio T. Sewell and Justin P. Hardick and Paul W. Blair and Chris D. Heaney and Andrew Pekosz, David L. Thomas}, url = {https://www.medrxiv.org/content/10.1101/2020.10.07.20208520v1 }, doi = {https://doi.org/10.1101/2020.10.07.20208520 }, year = {2020}, date = {2020-10-12}, journal = { medRxiv - The Preprint Server for Health Sciences}, abstract = {Abstract In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.}, note = {This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others. |
Mujugira, Andrew; Baeten, Jared M; Hodges-Mameletzis, Ioannis; Haberer, Jessica E Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen Journal Article Drugs, 80 , pp. 1881–1888 , 2020. @article{Mujugira2020b, title = {Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen}, author = {Andrew Mujugira and Jared M. Baeten and Ioannis Hodges-Mameletzis and Jessica E. Haberer }, url = {https://link.springer.com/article/10.1007/s40265-020-01419-4}, doi = {https://doi.org/10.1007/s40265-020-01419-4}, year = {2020}, date = {2020-10-10}, journal = {Drugs}, volume = {80}, pages = {1881–1888 }, abstract = {Abstract Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President’s Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in clinical trials, open-label extension studies and demonstration projects. Thus, most PrEP efficacy and safety data are based on FTC/TDF use in heterosexual women and men, men who have sex with men, and people who inject drugs. However, generic 3TC/TDF is less expensive than FTC/TDF, is already available in supply chains for HIV drugs, and has 60–70% of the global adult market share, making it particularly appealing in settings with limited availability or affordability of FTC/TDF. Compelling indirect evidence suggests that scaling up use of 3TC/TDF is potentially cost saving for HIV programs in settings where restricting drug choice to FTC/TDF would delay PrEP implementation. Guideline committees and public health decision-makers in countries should encourage flexibility in PrEP drug selection, support off-label use of 3TC/TDF, and approve use of generic formulations to decrease the cost of PrEP medications and accelerate PrEP delivery through the public and private sectors.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President’s Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in clinical trials, open-label extension studies and demonstration projects. Thus, most PrEP efficacy and safety data are based on FTC/TDF use in heterosexual women and men, men who have sex with men, and people who inject drugs. However, generic 3TC/TDF is less expensive than FTC/TDF, is already available in supply chains for HIV drugs, and has 60–70% of the global adult market share, making it particularly appealing in settings with limited availability or affordability of FTC/TDF. Compelling indirect evidence suggests that scaling up use of 3TC/TDF is potentially cost saving for HIV programs in settings where restricting drug choice to FTC/TDF would delay PrEP implementation. Guideline committees and public health decision-makers in countries should encourage flexibility in PrEP drug selection, support off-label use of 3TC/TDF, and approve use of generic formulations to decrease the cost of PrEP medications and accelerate PrEP delivery through the public and private sectors. |
Nakalega, Rita; Mukiza, Nelson; Kiwanuka, George; Makanga-Kakumba, Ronald; Menge, Robert; Kataike, Hajira; Maena, Joel; Akello, Carolyne; Atuhaire, Patience; Matovu-Kiweewa, Flavia; Ndikuno-Kuteesa, Cynthia; Debem, Henry; Mujugira, Andrew Non-uptake of viral load testing among people receiving HIV treatment in Gomba district, rural Uganda Journal Article BMC Infectious Diseases volume, 20 (1), pp. 727, 2020. @article{Nakalega2020, title = {Non-uptake of viral load testing among people receiving HIV treatment in Gomba district, rural Uganda}, author = {Rita Nakalega and Nelson Mukiza and George Kiwanuka and Ronald Makanga-Kakumba and Robert Menge and Hajira Kataike and Joel Maena and Carolyne Akello and Patience Atuhaire and Flavia Matovu-Kiweewa and Cynthia Ndikuno-Kuteesa and Henry Debem and Andrew Mujugira }, url = {https://link.springer.com/article/10.1186/s12879-020-05461-1}, doi = {https://doi.org/10.1186/s12879-020-05461-1}, year = {2020}, date = {2020-10-06}, journal = {BMC Infectious Diseases volume}, volume = {20}, number = {1}, pages = {727}, abstract = {Abstract Background Viral load (VL) testing is the gold-standard approach for monitoring human immunodeficiency virus (HIV) treatment success and virologic failure, but uptake is suboptimal in resource-limited and rural settings. We conducted a cross-sectional study of risk factors for non-uptake of VL testing in rural Uganda. Methods We conducted a cross-sectional analysis of uptake of VL testing among randomly selected people with HIV (PWH) receiving anti-retroviral treatment (ART) for at least 6 months at all eight primary health centers in Gomba district, rural Uganda. Socio-demographic and clinical data were extracted from medical records for the period January to December 2017. VL testing was routinely performed 6 months after ART initiation and 12 months thereafter for PWH stable on ART. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-uptake of VL testing (the primary outcome). Results Of 414 PWH, 60% were female, and the median age was 40 years (interquartile range [IQR] 31–48). Most (62.3%) had been on ART > 2 years, and the median duration of treatment was 34 months (IQR 14–55). Thirty three percent did not receive VL testing: 36% of women and 30% of men. Shorter duration of ART (≤2 years) (adjusted odds ratio [AOR] 2.38; 95% CI:1.37–4.12; p = 0.002), younger age 16–30 years (AOR 2.74; 95% CI:1.44–5.24; p = 0.002) and 31–45 years (AOR 1.92; 95% CI 1.12–3.27; p = 0.017), and receipt of ART at Health Center IV (AOR 2.85; 95% CI: 1.78–4.56; p < 0.001) were significantly associated with non-uptake of VL testing. Conclusions One-in-three PWH on ART missed VL testing in rural Uganda. Strategies to improve coverage of VL testing, such as VL focal persons to flag missed tests, patient education and demand creation for VL testing are needed, particularly for recent ART initiates and younger persons on treatment, in order to attain the third Joint United Nations Program on HIV/AIDS (UNAIDS) 95–95-95 target – virologic suppression for 95% of PWH on ART.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Viral load (VL) testing is the gold-standard approach for monitoring human immunodeficiency virus (HIV) treatment success and virologic failure, but uptake is suboptimal in resource-limited and rural settings. We conducted a cross-sectional study of risk factors for non-uptake of VL testing in rural Uganda. Methods We conducted a cross-sectional analysis of uptake of VL testing among randomly selected people with HIV (PWH) receiving anti-retroviral treatment (ART) for at least 6 months at all eight primary health centers in Gomba district, rural Uganda. Socio-demographic and clinical data were extracted from medical records for the period January to December 2017. VL testing was routinely performed 6 months after ART initiation and 12 months thereafter for PWH stable on ART. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-uptake of VL testing (the primary outcome). Results Of 414 PWH, 60% were female, and the median age was 40 years (interquartile range [IQR] 31–48). Most (62.3%) had been on ART > 2 years, and the median duration of treatment was 34 months (IQR 14–55). Thirty three percent did not receive VL testing: 36% of women and 30% of men. Shorter duration of ART (≤2 years) (adjusted odds ratio [AOR] 2.38; 95% CI:1.37–4.12; p = 0.002), younger age 16–30 years (AOR 2.74; 95% CI:1.44–5.24; p = 0.002) and 31–45 years (AOR 1.92; 95% CI 1.12–3.27; p = 0.017), and receipt of ART at Health Center IV (AOR 2.85; 95% CI: 1.78–4.56; p < 0.001) were significantly associated with non-uptake of VL testing. Conclusions One-in-three PWH on ART missed VL testing in rural Uganda. Strategies to improve coverage of VL testing, such as VL focal persons to flag missed tests, patient education and demand creation for VL testing are needed, particularly for recent ART initiates and younger persons on treatment, in order to attain the third Joint United Nations Program on HIV/AIDS (UNAIDS) 95–95-95 target – virologic suppression for 95% of PWH on ART. |
Toms, Kieran; Potter, Harriet; Balaba, Martin; Parkes-Ratanshi, Rosalind Efficacy of HIV interventions in African fishing communities: A systematic review and qualitative synthesis Journal Article International Journal of Infectious Diseases, 101 (2020-10-02), pp. 326-333, 2020. @article{Toms2020, title = {Efficacy of HIV interventions in African fishing communities: A systematic review and qualitative synthesis}, author = {Kieran Toms and Harriet Potter and Martin Balaba and Rosalind Parkes-Ratanshi}, url = {https://www.sciencedirect.com/science/article/pii/S1201971220321925}, doi = {https://doi.org/10.1016/j.ijid.2020.09.1476}, year = {2020}, date = {2020-10-02}, journal = {International Journal of Infectious Diseases}, volume = {101}, number = {2020-10-02}, pages = {326-333}, abstract = {Abstract Objectives This systematic review aims to qualitatively synthesize existing evidence on the efficacy of HIV interventions in African fishing communities. Methods Five databases (NCBI PubMed, EMBASE, Web of Science Core Collection, The Cochrane Library, and CABI Global Health Database) were searched in March 2019 for eligible studies. All peer-reviewed papers with a defined HIV intervention explicitly mentioning African fishing communities were included. Outcomes included any measure of the efficacy of HIV interventions. Results Of 22,289 search results, data was extracted from 25 eligible studies that passed critical appraisal; seven involved HIV prevention, six HIV testing and counseling, three treatment, and nine combinations of more than one intervention. Findings include a high coverage of safe male circumcision (SMC) but low condom use among fisher folk, and a preference for PrEP over other HIV prevention services. Uptake of HIV testing and ART coverage are below levels required to reach UNAIDS 90-90-90 targets, and there is a high demand for ART and HIV self-testing kits. Conclusions Greater provision of services to combat HIV, specifically amongst fishing communities, is required; there is limited information on retaining fisher folk in care and achieving an undetectable viral load. Interventions tailored to individual fishing populations, offered in parallel to education or counseling services are likely to be most effective. Use of innovations, including mobile health and medical drones, could assist these hard-to-reach populations. Our findings will inform future HIV service provision in fishing communities.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Objectives This systematic review aims to qualitatively synthesize existing evidence on the efficacy of HIV interventions in African fishing communities. Methods Five databases (NCBI PubMed, EMBASE, Web of Science Core Collection, The Cochrane Library, and CABI Global Health Database) were searched in March 2019 for eligible studies. All peer-reviewed papers with a defined HIV intervention explicitly mentioning African fishing communities were included. Outcomes included any measure of the efficacy of HIV interventions. Results Of 22,289 search results, data was extracted from 25 eligible studies that passed critical appraisal; seven involved HIV prevention, six HIV testing and counseling, three treatment, and nine combinations of more than one intervention. Findings include a high coverage of safe male circumcision (SMC) but low condom use among fisher folk, and a preference for PrEP over other HIV prevention services. Uptake of HIV testing and ART coverage are below levels required to reach UNAIDS 90-90-90 targets, and there is a high demand for ART and HIV self-testing kits. Conclusions Greater provision of services to combat HIV, specifically amongst fishing communities, is required; there is limited information on retaining fisher folk in care and achieving an undetectable viral load. Interventions tailored to individual fishing populations, offered in parallel to education or counseling services are likely to be most effective. Use of innovations, including mobile health and medical drones, could assist these hard-to-reach populations. Our findings will inform future HIV service provision in fishing communities. |
Pullen, Matthew F; Hullsiek, Katherine Huppler; Rhein, Joshua; Musubire, Abdu K; Tugume, Lillian; Nuwagira, Edwin; Abassi, Mahsa; Ssebambulidde, Kenneth; Mpoza, Edward; Kiggundu, Ruben; Akampurira, Andrew; Nabeta, Henry W; Evans, Charlotte Schutzand Emily E; Rajasingham, Radha; Skipper, Caleb P; Pastick, Katelyn A; Williams, Darlisha A; Morawski, Bozena M; Bangdiwala, Ananta S; Meintjes, Graeme; ad Meya, Conrad Muzoora David B; for the team David R Boulware, ASTRO-CM Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials Journal Article Clinical Infectious Diseases, 71 (7), pp. e45–e49, , 2020. @article{Pullen2020b, title = {Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials }, author = {Matthew F Pullen and Katherine Huppler Hullsiek and Joshua Rhein and Abdu K Musubire and Lillian Tugume and Edwin Nuwagira and Mahsa Abassi and Kenneth Ssebambulidde and Edward Mpoza and Ruben Kiggundu and Andrew Akampurira and Henry W Nabeta and Charlotte Schutzand Emily E Evans and Radha Rajasingham and Caleb P Skipper and Katelyn A Pastick and Darlisha A Williams and Bozena M Morawski and Ananta S Bangdiwala and Graeme Meintjes and Conrad Muzoora ad David B Meya and David R Boulware ,for the ASTRO-CM team}, url = {https://academic.oup.com/cid/article-abstract/71/7/e45/5698219}, doi = {https://doi.org/10.1093/cid/ciaa016}, year = {2020}, date = {2020-10-01}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {7}, pages = {e45–e49, }, abstract = {Abstract Background In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks. Methods We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010–2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days. Results Mortality through 18 weeks was 37% for EFA > = 0.60 (n = 170), 36% for 0.40–0.59 (n = 182), 39% for 0.30–0.39 (n = 112), 35% for 0.20–0.29 (n = 87), and 50% for those with EFA < 0.20 CFU/mL/day (n = 187). The hazard ratio for 18-week mortality, comparing those with EFA < 0.20 to those with EFA > = 0.20, was 1.60 (95% confidence interval, 1.25, 2.04; P = .002). The lowest EFA group had lower median CD4 T-cell counts (P < .01) and lower proportion of patients with CSF pleocytosis (P < .001). Conclusions EFA is associated with all-cause mortality in cryptococcal meningitis. An EFA threshold of > = 0.20 log10 CFU/mL/day was associated with similar 18-week mortality (37%) compared to 50% mortality with EFA < 0.20. This EFA threshold may be considered a target for a surrogate endpoint. This builds upon existing studies to validate EFA as a surrogate endpoint. cryptococcus, meningitis, cryptococcal meningitis, early fungicidal activity, surrogate endpoint Topic: amphotericin b cryptococcal meningitis drug clearance cerebrospinal fluid cryptococcus mortality surrogate endpoints }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks. Methods We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010–2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days. Results Mortality through 18 weeks was 37% for EFA > = 0.60 (n = 170), 36% for 0.40–0.59 (n = 182), 39% for 0.30–0.39 (n = 112), 35% for 0.20–0.29 (n = 87), and 50% for those with EFA < 0.20 CFU/mL/day (n = 187). The hazard ratio for 18-week mortality, comparing those with EFA < 0.20 to those with EFA > = 0.20, was 1.60 (95% confidence interval, 1.25, 2.04; P = .002). The lowest EFA group had lower median CD4 T-cell counts (P < .01) and lower proportion of patients with CSF pleocytosis (P < .001). Conclusions EFA is associated with all-cause mortality in cryptococcal meningitis. An EFA threshold of > = 0.20 log10 CFU/mL/day was associated with similar 18-week mortality (37%) compared to 50% mortality with EFA < 0.20. This EFA threshold may be considered a target for a surrogate endpoint. This builds upon existing studies to validate EFA as a surrogate endpoint. cryptococcus, meningitis, cryptococcal meningitis, early fungicidal activity, surrogate endpoint Topic: amphotericin b cryptococcal meningitis drug clearance cerebrospinal fluid cryptococcus mortality surrogate endpoints |
Stalter, Randy; MPH, ; Mugwanya, Kenneth; Thomas, MS Katherine; Donnell, Deborah; Mujugira, Andrew; Celum, Kenneth Ngure Connie; Kidoguchi, Lara; Bukusi, Elizabeth; Baeten, Jared; Heffron, Renee; the Team, Partners Demonstration Project Sexual Behaviors After PrEP Discontinuation Among HIV Serodiscordant Couples in Kenya and Uganda Journal Article Journal of Acquired Immune Deficiency Syndromes (1999), 85 (2), pp. 174–181, 2020. @article{Stalter2020, title = {Sexual Behaviors After PrEP Discontinuation Among HIV Serodiscordant Couples in Kenya and Uganda}, author = {Randy Stalter and MPH and Kenneth Mugwanya and MS Katherine Thomas and Deborah Donnell and Andrew Mujugira and Kenneth Ngure Connie Celum and Lara Kidoguchi and Elizabeth Bukusi and Jared Baeten and Renee Heffron and the Partners Demonstration Project Team}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495981/}, doi = {doi: 10.1097/QAI.0000000000002434}, year = {2020}, date = {2020-10-01}, journal = {Journal of Acquired Immune Deficiency Syndromes (1999)}, volume = {85}, number = {2}, pages = {174–181}, abstract = {Background: A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partner's adherence to antiretroviral therapy (ART) for prevention. Setting: Kenya and Uganda. Methods: Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partners' age and sex. Results: We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts [level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI): 0.87 to 1.04; trend aRR = 1.00, 95% CI: 0.99 to 1.01] or condomless sex acts (level aRR = 0.97, 95% CI: 0.81 to 1.17; trend aRR = 1.00, 95% CI: 0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups. Conclusions: PrEP discontinuation seems to result in no significant changes in couples' sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples. Key Words: HIV, prevention, pre-exposure prophylaxis, discontinuation, serodiscordant couples, sexual behaviors}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partner's adherence to antiretroviral therapy (ART) for prevention. Setting: Kenya and Uganda. Methods: Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partners' age and sex. Results: We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts [level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI): 0.87 to 1.04; trend aRR = 1.00, 95% CI: 0.99 to 1.01] or condomless sex acts (level aRR = 0.97, 95% CI: 0.81 to 1.17; trend aRR = 1.00, 95% CI: 0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups. Conclusions: PrEP discontinuation seems to result in no significant changes in couples' sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples. Key Words: HIV, prevention, pre-exposure prophylaxis, discontinuation, serodiscordant couples, sexual behaviors |
EM, Martyn; AS, Bangdiwala; E, Kagimu; MK, Rutakingirwa; J, Kasibante; M, Okirwoth; G, Stead; V, Wadda; MF, Pullen; TD, Bold; DB, Meya; DR, Boulware; EM, Martyn; AS, Bangdiwala; E, Kagimu; MK, Rutakingirwa; J, Kasibante; M, Okirwoth; G, Stead; V, Wadda; MF, Pullen; TD, Bold; ad DR, Meya DB Boulware; NC, Bahr; FV, Cresswell Clinical Infectious Diseases, pp. e00838-20, 2020. @article{EM2020, title = {Cerebrospinal fluid bacillary load by Xpert MTB/RIF Ultra PCR Cycle Threshold value predicts two-week mortality in HIV-associated tuberculous meningitis.}, author = {Martyn EM and Bangdiwala AS and Kagimu E and Rutakingirwa MK and Kasibante J and Okirwoth M and Stead G and Wadda V and Pullen MF and Bold TD and Meya DB and Boulware DR and Martyn EM and Bangdiwala AS and Kagimu E and Rutakingirwa MK and Kasibante J and Okirwoth M and Stead G and Wadda V and Pullen MF and Bold TD and Meya DB ad Boulware DR and Bahr NC and Cresswell FV}, url = {https://europepmc.org/article/med/32986792}, doi = {DOI: 10.1093/cid/ciaa1444 }, year = {2020}, date = {2020-09-28}, journal = {Clinical Infectious Diseases}, pages = {e00838-20}, abstract = { Abstract Background The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated PCR assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate TB bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. Methods We prospectively enrolled 102 HIV-positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between CT and baseline clinical and CSF parameters. Results Subjects with Ct values in the low tertile (i.e. high bacillary load) had 57% 2-week mortality; worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra-negative (30%) probable TBM cases (p=.01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with medium to low category trending towards worse 2-week survival (42%) compared with very low (28%), trace (26%) and negative (30%) categories (p=.48). Ct tertile was significantly associated with baseline CSF lactate (p=.03). Conclusions High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated PCR assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate TB bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. Methods We prospectively enrolled 102 HIV-positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between CT and baseline clinical and CSF parameters. Results Subjects with Ct values in the low tertile (i.e. high bacillary load) had 57% 2-week mortality; worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra-negative (30%) probable TBM cases (p=.01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with medium to low category trending towards worse 2-week survival (42%) compared with very low (28%), trace (26%) and negative (30%) categories (p=.48). Ct tertile was significantly associated with baseline CSF lactate (p=.03). Conclusions High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care. |
Nakalembe, Miriam; Makanga, Philippa; Kambugu, Andrew; Laker‐Oketta, Miriam; Huchko, Megan J; Martin, Jeffrey Cancer Medicine, 9 (22), pp. 8701-8712, 2020. @article{Nakalembe2020, title = {A public health approach to cervical cancer screening in Africa through community‐based self‐administered HPV testing and mobile treatment provision}, author = {Miriam Nakalembe and Philippa Makanga and Andrew Kambugu and Miriam Laker‐Oketta and Megan J. Huchko and Jeffrey Martin}, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.3468}, doi = { https://doi.org/10.1002/cam4.3468}, year = {2020}, date = {2020-09-23}, journal = {Cancer Medicine}, volume = {9}, number = {22}, pages = {8701-8712}, abstract = {Abstract The World Health Organization (WHO) refers to cervical cancer as a public health problem, and sub‐Saharan Africa bears the world's highest incidence. In the realm of screening, simplified WHO recommendations for low‐resource countries now present an opportunity for a public health approach to this public health problem. We evaluated the feasibility of such a public health approach to cervical cancer screening that features community‐based self‐administered HPV testing and mobile treatment provision. In two rural districts of western‐central Uganda, Village Health Team members led community mobilization for cervical cancer screening fairs in their communities, which offered self‐collection of vaginal samples for high‐risk human papillomavirus (hrHPV) testing. High‐risk human papillomavirus‐positive women were re‐contacted and referred for treatment with cryotherapy by a mobile treatment unit in their community. We also determined penetrance of the mobilization campaign message by interviewing a probability sample of adult women in study communities about the fair and their attendance. In 16 communities, 2142 women attended the health fairs; 1902 were eligible for cervical cancer screening of which 1892 (99.5%) provided a self‐collected vaginal sample. Among the 393 (21%) women with detectable hrHPV, 89% were successfully contacted about their results, of which 86% returned for treatment by a mobile treatment team. Most of the women in the community (93%) reported hearing about the fair, and among those who had heard of the fair, 68% attended. This public health approach to cervical cancer screening was feasible, effectively penetrated the communities, and was readily accepted by community women. The findings support further optimization and evaluation of this approach as a means of scaling up cervical cancer control in low‐resource settings.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract The World Health Organization (WHO) refers to cervical cancer as a public health problem, and sub‐Saharan Africa bears the world's highest incidence. In the realm of screening, simplified WHO recommendations for low‐resource countries now present an opportunity for a public health approach to this public health problem. We evaluated the feasibility of such a public health approach to cervical cancer screening that features community‐based self‐administered HPV testing and mobile treatment provision. In two rural districts of western‐central Uganda, Village Health Team members led community mobilization for cervical cancer screening fairs in their communities, which offered self‐collection of vaginal samples for high‐risk human papillomavirus (hrHPV) testing. High‐risk human papillomavirus‐positive women were re‐contacted and referred for treatment with cryotherapy by a mobile treatment unit in their community. We also determined penetrance of the mobilization campaign message by interviewing a probability sample of adult women in study communities about the fair and their attendance. In 16 communities, 2142 women attended the health fairs; 1902 were eligible for cervical cancer screening of which 1892 (99.5%) provided a self‐collected vaginal sample. Among the 393 (21%) women with detectable hrHPV, 89% were successfully contacted about their results, of which 86% returned for treatment by a mobile treatment team. Most of the women in the community (93%) reported hearing about the fair, and among those who had heard of the fair, 68% attended. This public health approach to cervical cancer screening was feasible, effectively penetrated the communities, and was readily accepted by community women. The findings support further optimization and evaluation of this approach as a means of scaling up cervical cancer control in low‐resource settings. |
Skipper, Caleb P; Atukunda, Mucunguzi; Stadelman, Anna; Engen, Nicole W; Bangdiwala, Ananta S; Hullsiek, Katherine H; Abassi, Mahsa; Rhein, Joshua; Nicol, Melanie R; Laker, Eva; Williams, Darlisha A; Mannino, Raphael; Matkovits, Theresa; Meya, David B; Boulware, David R Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B. Antimicrob Agents Chemother. Journal Article Antimicrobial Agents and Chemotherapy, 64 (10), pp. e00838-20, 2020. @article{Skipper2020b, title = {Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B. Antimicrob Agents Chemother.}, author = {Caleb P. Skipper and Mucunguzi Atukunda and Anna Stadelman and Nicole W. Engen and Ananta S. Bangdiwala and Katherine H. Hullsiek and Mahsa Abassi and Joshua Rhein and Melanie R. Nicol and Eva Laker and Darlisha A. Williams and Raphael Mannino and Theresa Matkovits and David B. Meya and David R. Boulware}, url = {https://aac.asm.org/content/64/10/e00838-20.abstract}, doi = {DOI: 10.1128/AAC.00838-20}, year = {2020}, date = {2020-09-21}, journal = {Antimicrobial Agents and Chemotherapy}, volume = {64}, number = {10}, pages = {e00838-20}, abstract = {ABSTRACT Amphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin B deoxycholate (cAMB) formulation has oral bioavailability, efficacy in an animal model, and minimal toxicity due to targeted drug delivery into macrophages, where intracellular fungi reside. We conducted a phase I, ascending-dose trial of cAMB administered at 1.0 g, 1.5 g, or 2.0 g per day in 4 to 6 divided doses among HIV-positive survivors of cryptococcosis (n = 9 per cohort). We assessed the tolerability of cAMB and the adverse events (AEs) associated with cAMB treatment over 3 days. A second trial (n = 9) assessed the tolerability of 1.5 g/day given for 7 days. In the single-ascending-dose study, all subjects received their full daily dose without vomiting (100% tolerability). The cohort receiving 1.0 g had 4 transient clinical AEs in 2 subjects within 48 h and 8 laboratory AEs (n = 6 grade 2, n = 2 grade 1). The cohort receiving 1.5 g had 7 clinical AEs in 1 subject attributed to acute gastroenteritis (n = 4 grade 2) and 5 laboratory AEs (n = 1 grade 2). The cohort receiving 2.0 g had 20 clinical AEs among 5 subjects within 48 h (n = 3 grade 2) and 11 laboratory AEs (n = 2 grade 2, n = 1 grade 3). From a qualitative survey, 26 of 27 subjects (96%) preferred their experience with oral cAMB over their prior experience with intravenous (i.v.) AMB. The second, multiple-dose cohort received 1.5 g/day for 1 week, with 98.4% (248/252) of the doses being taken. Overall, 5 clinical AEs (n = 5 grade 1) and 6 laboratory AEs (n = 6 grade 1) occurred without kidney toxicity. Oral cAMB was well tolerated when given in 4 to 6 divided daily doses without the toxicities commonly seen with i.v. AMB. (This study has been registered at ClinicalTrials.gov under registration no. NCT04031833.)}, keywords = {}, pubstate = {published}, tppubtype = {article} } ABSTRACT Amphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin B deoxycholate (cAMB) formulation has oral bioavailability, efficacy in an animal model, and minimal toxicity due to targeted drug delivery into macrophages, where intracellular fungi reside. We conducted a phase I, ascending-dose trial of cAMB administered at 1.0 g, 1.5 g, or 2.0 g per day in 4 to 6 divided doses among HIV-positive survivors of cryptococcosis (n = 9 per cohort). We assessed the tolerability of cAMB and the adverse events (AEs) associated with cAMB treatment over 3 days. A second trial (n = 9) assessed the tolerability of 1.5 g/day given for 7 days. In the single-ascending-dose study, all subjects received their full daily dose without vomiting (100% tolerability). The cohort receiving 1.0 g had 4 transient clinical AEs in 2 subjects within 48 h and 8 laboratory AEs (n = 6 grade 2, n = 2 grade 1). The cohort receiving 1.5 g had 7 clinical AEs in 1 subject attributed to acute gastroenteritis (n = 4 grade 2) and 5 laboratory AEs (n = 1 grade 2). The cohort receiving 2.0 g had 20 clinical AEs among 5 subjects within 48 h (n = 3 grade 2) and 11 laboratory AEs (n = 2 grade 2, n = 1 grade 3). From a qualitative survey, 26 of 27 subjects (96%) preferred their experience with oral cAMB over their prior experience with intravenous (i.v.) AMB. The second, multiple-dose cohort received 1.5 g/day for 1 week, with 98.4% (248/252) of the doses being taken. Overall, 5 clinical AEs (n = 5 grade 1) and 6 laboratory AEs (n = 6 grade 1) occurred without kidney toxicity. Oral cAMB was well tolerated when given in 4 to 6 divided daily doses without the toxicities commonly seen with i.v. AMB. (This study has been registered at ClinicalTrials.gov under registration no. NCT04031833.) |
Eke, Ahizechukwu C; Olagunju, Adeniyi; Momper, Jeremiah; Penazzato, Martina; Abrams, Elaine J; Best, Brookie M; Capparelli, Edmund V; Bekker, Adrie; Belew, Yodit; Kiser, Jennifer J; Struble, Kimberly; Taylor, Graham; Waitt, Catriona; Mirochnick, Mark; Cressey, Tim R; Colbers, Angela; participants of the workshop on to Optimize, WHO‐IMPAACT “Approaches; in Pregnant, Accelerate Pharmacokinetic Studies; Women”, Lactating Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons from HIV: A Consensus Statement Journal Article Clinical Pharmacology & Therapeutics, 2020. @article{Eke2020, title = {Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons from HIV: A Consensus Statement}, author = {Ahizechukwu C. Eke and Adeniyi Olagunju and Jeremiah Momper and Martina Penazzato and Elaine J. Abrams and Brookie M. Best and Edmund V. Capparelli and Adrie Bekker and Yodit Belew and Jennifer J. Kiser and Kimberly Struble and Graham Taylor and Catriona Waitt and Mark Mirochnick and Tim R. Cressey and Angela Colbers and participants of the WHO‐IMPAACT workshop on “Approaches to Optimize and Accelerate Pharmacokinetic Studies in Pregnant and Lactating Women” }, url = {https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2048}, doi = {https://doi.org/10.1002/cpt.2048}, year = {2020}, date = {2020-09-15}, journal = {Clinical Pharmacology & Therapeutics}, abstract = { Abstract Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)–convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low‐income and middle‐income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)–convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low‐income and middle‐income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical. |
Ngbapai, Jackslina Gaaniri; Izudi, Jonathan; Okoboi, Stephen International Breastfeeding Journal, 15 (1), pp. 78, 2020. @article{Ngbapai2020, title = {Cessation of breastfeeding and associated factors in the era of elimination of mother to child transmission of HIV at Ndejje health center, Uganda: a retrospective cohort study}, author = {Jackslina Gaaniri Ngbapai and Jonathan Izudi and Stephen Okoboi }, url = {https://internationalbreastfeedingjournal.biomedcentral.com/articles/10.1186/s13006-020-00323-7}, doi = {https://doi.org/10.1186/s13006-020-00323-7}, year = {2020}, date = {2020-09-07}, journal = {International Breastfeeding Journal}, volume = {15}, number = {1}, pages = {78}, abstract = {Abstract Background Breastfeeding an infant exposed to Human Immunodeficiency Virus (HIV) carries the risk of HIV acquisition whilst not breastfeeding poses a higher risk of death from malnutrition, diarrhea, and pneumonia. In Uganda, mothers living with HIV are encouraged to discontinue breastfeeding at 12 months but data are limited. We examined the frequency and factors associated with cessation of breastfeeding at 1 year among mothers living with HIV at Ndejje Health Center IV, a large peri-urban health facility in Uganda. Methods This retrospective cohort study involved all mothers living with HIV and enrolled in HIV care for ≥12 months between June 2014 and June 2018. We abstracted data from registers, held focus group discussions with mothers living with HIV and key informant interviews with healthcare providers. Cessation of breastfeeding was defined as the proportion of mothers living with HIV who had discontinued breastfeeding at 1 year. We summarized quantitative data descriptively, tested differences in outcome using Chi-square and t - tests, and established independently associated factors using modified Poisson regression analysis at 5% statistical significance level. We thematically analyzed qualitative data to enrich and triangulate the quantitative results. Results Of 235 participants, 150 (63.8%) had ceased breastfeeding at 1 year and this was independently associated with the infant being male (Adjusted Risk Ratio [aRR] 1.25, 95% confidence interval [CI] 1.04, 1.50), the mother being multiparous (aRR 1.26, 95% CI 1.04–1.53), and the initiation of breastfeeding being on the same-day as birth (aRR 0.06, 95% CI 0.01–0.41). The reasons for ceasing breastfeeding included male infants over breastfeed than females, maternal literacy and knowledge adequacy about breastfeeding, support and reminders from the partner, and boys can bite once they get teeth. Conclusion Suboptimal proportion of infants were ceased from breastfeeding at 1 year and this might increase the risk of mother to child transmission of HIV. Cessation of breastfeeding was more likely among male infants and multiparous mothers but less likely when breastfeeding was initiated on the same-day as birth. Interventions to enhance cessation of breastfeeding should target none multiparous mothers and those with female infants.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Breastfeeding an infant exposed to Human Immunodeficiency Virus (HIV) carries the risk of HIV acquisition whilst not breastfeeding poses a higher risk of death from malnutrition, diarrhea, and pneumonia. In Uganda, mothers living with HIV are encouraged to discontinue breastfeeding at 12 months but data are limited. We examined the frequency and factors associated with cessation of breastfeeding at 1 year among mothers living with HIV at Ndejje Health Center IV, a large peri-urban health facility in Uganda. Methods This retrospective cohort study involved all mothers living with HIV and enrolled in HIV care for ≥12 months between June 2014 and June 2018. We abstracted data from registers, held focus group discussions with mothers living with HIV and key informant interviews with healthcare providers. Cessation of breastfeeding was defined as the proportion of mothers living with HIV who had discontinued breastfeeding at 1 year. We summarized quantitative data descriptively, tested differences in outcome using Chi-square and t - tests, and established independently associated factors using modified Poisson regression analysis at 5% statistical significance level. We thematically analyzed qualitative data to enrich and triangulate the quantitative results. Results Of 235 participants, 150 (63.8%) had ceased breastfeeding at 1 year and this was independently associated with the infant being male (Adjusted Risk Ratio [aRR] 1.25, 95% confidence interval [CI] 1.04, 1.50), the mother being multiparous (aRR 1.26, 95% CI 1.04–1.53), and the initiation of breastfeeding being on the same-day as birth (aRR 0.06, 95% CI 0.01–0.41). The reasons for ceasing breastfeeding included male infants over breastfeed than females, maternal literacy and knowledge adequacy about breastfeeding, support and reminders from the partner, and boys can bite once they get teeth. Conclusion Suboptimal proportion of infants were ceased from breastfeeding at 1 year and this might increase the risk of mother to child transmission of HIV. Cessation of breastfeeding was more likely among male infants and multiparous mothers but less likely when breastfeeding was initiated on the same-day as birth. Interventions to enhance cessation of breastfeeding should target none multiparous mothers and those with female infants. |
Galukande, Moses; Were, Leonard Francis; Kigozi, Joanita; Kahendeke, Carol; Muganzi, Alex; Kambugu, Andrew Closing the Gap toward Zero Tetanus Infection for Voluntary Medical Male Circumcision: Seven Case Reports and a Review of the Literature Journal Article Surgical Infections, 21 (7), pp. 599-607, 2020. @article{Galukande2020, title = {Closing the Gap toward Zero Tetanus Infection for Voluntary Medical Male Circumcision: Seven Case Reports and a Review of the Literature}, author = {Moses Galukande and Leonard Francis Were and Joanita Kigozi and Carol Kahendeke and Alex Muganzi and Andrew Kambugu}, url = {https://www.liebertpub.com/doi/abs/10.1089/sur.2020.103}, doi = {https://doi.org/10.1089/sur.2020.103}, year = {2020}, date = {2020-09-01}, journal = {Surgical Infections}, volume = {21}, number = {7}, pages = {599-607}, abstract = {Abstract Background: Voluntary medical male circumcision (VMMC) is important for HIV prevention, providing up to 60% protection. Although VMMC is usually a safe procedure, it is not free of associated serious adverse events. In the Uganda VMMC program, which is available to males 10 years of age and older, 11 individuals were reported with tetanus infection out of almost 3.5 million circumcisions over an eight-year period (2009–2018). The majority had received tetanus vaccination prior to VMMC. Disproportionately and statistically significantly, the elastic collar compression method accounted for half the tetanus infection cases, despite contributing to only less than 10% of circumcisions done. This article describes gaps in presumed tetanus vaccination (TTV) protection along with relevant discussions and recommendations. Case Presentations: We present seven tetanus case reports and a review of the literature. We were guided by a pre-determined thematic approach, focusing on immune response to TTV in the context of common infections and infestations in a tropical environment that may impair immune response to TTV. It is apparent in the available literature that the following (mostly tropical neglected infections) sufficiently impair antibody response to TTV: human immunodefiency virus (HIV), pulmonary tuberculosis, nematode infections, and schistosomiasis. Conclusions: One of seven patients died (14% case fatality). Individuals with prior exposure to certain infection(s) may not mount adequate antibody response to TTV sufficient to protect against acquiring tetanus. Therefore, TTV may not confer absolute protection against tetanus infection in these individuals. More needs to be done to ensure everyone is fully protected against tetanus, especially in the regions where risk of tetanus is heightened. We need to characterize the high-risk individuals (poor responders to TTV) and design targeted protective measures.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: Voluntary medical male circumcision (VMMC) is important for HIV prevention, providing up to 60% protection. Although VMMC is usually a safe procedure, it is not free of associated serious adverse events. In the Uganda VMMC program, which is available to males 10 years of age and older, 11 individuals were reported with tetanus infection out of almost 3.5 million circumcisions over an eight-year period (2009–2018). The majority had received tetanus vaccination prior to VMMC. Disproportionately and statistically significantly, the elastic collar compression method accounted for half the tetanus infection cases, despite contributing to only less than 10% of circumcisions done. This article describes gaps in presumed tetanus vaccination (TTV) protection along with relevant discussions and recommendations. Case Presentations: We present seven tetanus case reports and a review of the literature. We were guided by a pre-determined thematic approach, focusing on immune response to TTV in the context of common infections and infestations in a tropical environment that may impair immune response to TTV. It is apparent in the available literature that the following (mostly tropical neglected infections) sufficiently impair antibody response to TTV: human immunodefiency virus (HIV), pulmonary tuberculosis, nematode infections, and schistosomiasis. Conclusions: One of seven patients died (14% case fatality). Individuals with prior exposure to certain infection(s) may not mount adequate antibody response to TTV sufficient to protect against acquiring tetanus. Therefore, TTV may not confer absolute protection against tetanus infection in these individuals. More needs to be done to ensure everyone is fully protected against tetanus, especially in the regions where risk of tetanus is heightened. We need to characterize the high-risk individuals (poor responders to TTV) and design targeted protective measures. |
Shah, Maunank; Sonia Paradis, Joshua Betz ; Natalie Beylis, Renu Bharadwaj ; Caceres, Tatiana; Gotuzzo, Eduardo; Joloba, Moses; Mave, Vidya; Nakiyingi, Lydia; Nicol, Mark P; Pradhan, Neeta; King, Bonnie; Armstrong, Derek; Knecht, Deborah; Maus, Courtney E; Cooper, Charles K; Dorman, Susan E; Manabe, Yukari C Clinical Infectious Diseases, 71 (5), pp. 1161–1167, 2020. @article{Shah2020, title = {Multicenter Study of the Accuracy of the BD MAX Multidrug-resistant Tuberculosis Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated With Resistance to Rifampin and Isoniazid}, author = {Maunank Shah and Sonia Paradis, Joshua Betz and Natalie Beylis, Renu Bharadwaj and Tatiana Caceres and Eduardo Gotuzzo and Moses Joloba and Vidya Mave and Lydia Nakiyingi and Mark P Nicol and Neeta Pradhan and Bonnie King and Derek Armstrong and Deborah Knecht and Courtney E Maus and Charles K Cooper and Susan E Dorman and Yukari C Manabe}, url = {https://academic.oup.com/cid/article/71/5/1161/5574845?login=true}, doi = {https://doi.org/10.1093/cid/ciz932}, year = {2020}, date = {2020-09-01}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {5}, pages = {1161–1167}, abstract = {Abstract Background Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB) and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX multidrug-resistant (MDR)-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. Methods Outpatient adults with signs/symptoms of pulmonary TB were prospectively enrolled. Sputum smear microscopy and BD MAX were performed on a single raw sputum, which was then processed for culture and phenotypic drug susceptibility testing (DST), BD MAX, and Xpert MTB/RIF (Xpert). Results 1053 participants with presumptive TB were enrolled (47% female; 32% with human immunodeficiency virus). In patients with confirmed TB, BD MAX sensitivity was 93% (262/282 [95% CI, 89–95%]); specificity was 97% (593/610 [96–98%]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175 [98–100%]) for smear-positive samples (fluorescence microscopy), and 81% (87/107 [73–88%]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274 [87–94%]) for BD MAX and 90% (246/274 [86–93%]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared with phenotypic DST were 90% (9/10 [60–98%]) and 95% (211/222 [91–97%]), respectively. Sensitivity and specificity for detection of INH resistance were 82% (22/27 [63–92%]) and 100% (205/205 [98–100%]), respectively. Conclusions The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally. HIV, tuberculosis, Mycobacterium infections, diagnosis, multidrug, resistance Topic: phenotype hiv rifampin mutation pulmonary tuberculosis drug resistance india isoniazid microscopy, fluorescence mycobacterium tuberculosis peru south africa sputum tuberculosis uganda diagnosis multidrug-resistant tuberculosis tuberculosis and hiv infectious agent drug susceptibility analysis }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB) and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX multidrug-resistant (MDR)-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. Methods Outpatient adults with signs/symptoms of pulmonary TB were prospectively enrolled. Sputum smear microscopy and BD MAX were performed on a single raw sputum, which was then processed for culture and phenotypic drug susceptibility testing (DST), BD MAX, and Xpert MTB/RIF (Xpert). Results 1053 participants with presumptive TB were enrolled (47% female; 32% with human immunodeficiency virus). In patients with confirmed TB, BD MAX sensitivity was 93% (262/282 [95% CI, 89–95%]); specificity was 97% (593/610 [96–98%]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175 [98–100%]) for smear-positive samples (fluorescence microscopy), and 81% (87/107 [73–88%]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274 [87–94%]) for BD MAX and 90% (246/274 [86–93%]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared with phenotypic DST were 90% (9/10 [60–98%]) and 95% (211/222 [91–97%]), respectively. Sensitivity and specificity for detection of INH resistance were 82% (22/27 [63–92%]) and 100% (205/205 [98–100%]), respectively. Conclusions The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally. HIV, tuberculosis, Mycobacterium infections, diagnosis, multidrug, resistance Topic: phenotype hiv rifampin mutation pulmonary tuberculosis drug resistance india isoniazid microscopy, fluorescence mycobacterium tuberculosis peru south africa sputum tuberculosis uganda diagnosis multidrug-resistant tuberculosis tuberculosis and hiv infectious agent drug susceptibility analysis |
Mostafa, Heba H; Hardick, Justin; Morehead, Elizabeth; Miller, Jo-Anne; Gaydos, Charlotte A; Manabe, Yukari C Comparison of the analytical sensitivity of seven commonly used commercial SARS-CoV-2 automated molecular assays Journal Article Journal of Clinical Virology, 130 , pp. 104578, 2020. @article{Mostafa2020, title = {Comparison of the analytical sensitivity of seven commonly used commercial SARS-CoV-2 automated molecular assays}, author = {Heba H. Mostafa and Justin Hardick and Elizabeth Morehead and Jo-Anne Miller and Charlotte A. Gaydos and Yukari C. Manabe}, url = {https://www.sciencedirect.com/science/article/abs/pii/S1386653220303206}, doi = {https://doi.org/10.1016/j.jcv.2020.104578}, year = {2020}, date = {2020-09-01}, journal = {Journal of Clinical Virology}, volume = {130}, pages = {104578}, abstract = {Abstract The SARS-CoV-2 pandemic has challenged molecular microbiology laboratories to quickly implement and validate diagnostic assays and to expand testing capacity in a short timeframe. Multiple molecular diagnostic methods received FDA emergency use authorization (EUA) and were promptly validated for use nationwide. Several studies reported the analytical and/ or clinical evaluation of these molecular assays, however differences in the viral materials used for these evaluations complicated direct comparison of their analytical performance. In this study, we compared the analytical sensitivity (lower limit of detection, LOD) of seven commonly used qualitative SARS-CoV-2 molecular assays: the Abbott Molecular RealTime SARS-CoV-2 assay, the NeuMoDx™ SARS-CoV-2 assay, the Roche Cobas®SARS-CoV-2 assay, the BD SARS-CoV-2 reagents for BD MAX™ system, the Hologic Aptima® SARS-CoV-2 assay, the Xpert Xpress SARS-CoV-2 test, and the GenMark ePlex SARS-CoV-2 test. The comparison was performed utilizing a single positive clinical specimen that was serially diluted in viral transport media and quantified by the EUA approved SARS-CoV-2 droplet digital PCR (ddPCR) assay. Replicate samples were prepared and evaluated for reproducibility across different molecular assays with multiple replicates per assay. Our data demonstrated that the seven assays could detect 100 % of replicates at a nucleocapsid gene concentration of (N1 = 1,267 and N2 = 1,392) copies/mL. At a one log less concentration, the Abbott, the Roche, and the Xpert Xpress assays detected 100 % of the tested replicates.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract The SARS-CoV-2 pandemic has challenged molecular microbiology laboratories to quickly implement and validate diagnostic assays and to expand testing capacity in a short timeframe. Multiple molecular diagnostic methods received FDA emergency use authorization (EUA) and were promptly validated for use nationwide. Several studies reported the analytical and/ or clinical evaluation of these molecular assays, however differences in the viral materials used for these evaluations complicated direct comparison of their analytical performance. In this study, we compared the analytical sensitivity (lower limit of detection, LOD) of seven commonly used qualitative SARS-CoV-2 molecular assays: the Abbott Molecular RealTime SARS-CoV-2 assay, the NeuMoDx™ SARS-CoV-2 assay, the Roche Cobas®SARS-CoV-2 assay, the BD SARS-CoV-2 reagents for BD MAX™ system, the Hologic Aptima® SARS-CoV-2 assay, the Xpert Xpress SARS-CoV-2 test, and the GenMark ePlex SARS-CoV-2 test. The comparison was performed utilizing a single positive clinical specimen that was serially diluted in viral transport media and quantified by the EUA approved SARS-CoV-2 droplet digital PCR (ddPCR) assay. Replicate samples were prepared and evaluated for reproducibility across different molecular assays with multiple replicates per assay. Our data demonstrated that the seven assays could detect 100 % of replicates at a nucleocapsid gene concentration of (N1 = 1,267 and N2 = 1,392) copies/mL. At a one log less concentration, the Abbott, the Roche, and the Xpert Xpress assays detected 100 % of the tested replicates. |
Marais, Suzaan; Cresswell, Fiona V; Hamers, Raph L; te Brake, Lindsey H M; Ganiem, Ahmad R; Imran, Darma; Bangdiwala, Ananta; Martyn, Emily; Kasibante, John; Kagimu, Enock; Musubire, Abdu; Maharani, Kartika; Estiasari, Riwanti; Kusumaningrum, Ardiana; Kusumadjayanti, Nadytia; Yunivita, Vycke; Naidoo, Kogieleum; Lessells, Richard; Moosa, Yunus; Svensson, Elin M; Hullsiek, Katherine Huppler; Aarnoutse, Rob E; Boulware, David R; van Crevel, Reinout; Ruslami, Rovina; Meya, David B Wellcome Open Research, 4 , pp. 190, 2020. @article{Marais2020, title = {High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)}, author = {Suzaan Marais and Fiona V Cresswell and Raph L. Hamers and Lindsey H.M. te Brake and Ahmad R. Ganiem and Darma Imran and Ananta Bangdiwala and Emily Martyn and John Kasibante and Enock Kagimu and Abdu Musubire and Kartika Maharani and Riwanti Estiasari and Ardiana Kusumaningrum and Nadytia Kusumadjayanti and Vycke Yunivita and Kogieleum Naidoo and Richard Lessells and Yunus Moosa and Elin M. Svensson and Katherine Huppler Hullsiek and Rob E. Aarnoutse and David R. Boulware and Reinout van Crevel and Rovina Ruslami and David B. Meya}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542255/}, doi = {doi: 10.12688/wellcomeopenres.15565.2}, year = {2020}, date = {2020-08-25}, journal = {Wellcome Open Research}, volume = {4}, pages = {190}, abstract = {Abstract Background: Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), results in death or neurological disability in >50%, despite World Health Organisation recommended therapy. Current TBM regimen dosages are based on data from pulmonary TB alone. Evidence from recent phase II pharmacokinetic studies suggests that high dose rifampicin (R) administered intravenously or orally enhances central nervous system penetration and may reduce TBM associated mortality. We hypothesize that, among persons with TBM, high dose oral rifampicin (35 mg/kg) for 8 weeks will improve survival compared to standard of care (10 mg/kg), without excess adverse events. Protocol: We will perform a parallel group, randomised, placebo-controlled, double blind, phase III multicentre clinical trial comparing high dose oral rifampicin to standard of care. The trial will be conducted across five clinical sites in Uganda, South Africa and Indonesia. Participants are HIV-positive or negative adults with clinically suspected TBM, who will be randomised (1:1) to one of two arms: 35 mg/kg oral rifampicin daily for 8 weeks (in combination with standard dose isoniazid [H], pyrazinamide [Z] and ethambutol [E]) or standard of care (oral HRZE, containing 10 mg/kg/day rifampicin). The primary end-point is 6-month survival. Secondary end points are: i) 12-month survival ii) functional and neurocognitive outcomes and iii) safety and tolerability. Tertiary outcomes are: i) pharmacokinetic outcomes and ii) cost-effectiveness of the intervention. We will enrol 500 participants over 2.5 years, with follow-up continuing until 12 months post-enrolment. Discussion: Our best TBM treatment still results in unacceptably high mortality and morbidity. Strong evidence supports the increased cerebrospinal fluid penetration of high dose rifampicin, however conclusive evidence regarding survival benefit is lacking. This study will answer the important question of whether high dose oral rifampicin conveys a survival benefit in TBM in HIV-positive and -negative individuals from Africa and Asia. Trial registration: ISRCTN15668391 (17/06/2019) Keywords: Tuberculous Meningitis, TB, rifampicin, Xpert Ultra, HIV, treatment, RCT}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), results in death or neurological disability in >50%, despite World Health Organisation recommended therapy. Current TBM regimen dosages are based on data from pulmonary TB alone. Evidence from recent phase II pharmacokinetic studies suggests that high dose rifampicin (R) administered intravenously or orally enhances central nervous system penetration and may reduce TBM associated mortality. We hypothesize that, among persons with TBM, high dose oral rifampicin (35 mg/kg) for 8 weeks will improve survival compared to standard of care (10 mg/kg), without excess adverse events. Protocol: We will perform a parallel group, randomised, placebo-controlled, double blind, phase III multicentre clinical trial comparing high dose oral rifampicin to standard of care. The trial will be conducted across five clinical sites in Uganda, South Africa and Indonesia. Participants are HIV-positive or negative adults with clinically suspected TBM, who will be randomised (1:1) to one of two arms: 35 mg/kg oral rifampicin daily for 8 weeks (in combination with standard dose isoniazid [H], pyrazinamide [Z] and ethambutol [E]) or standard of care (oral HRZE, containing 10 mg/kg/day rifampicin). The primary end-point is 6-month survival. Secondary end points are: i) 12-month survival ii) functional and neurocognitive outcomes and iii) safety and tolerability. Tertiary outcomes are: i) pharmacokinetic outcomes and ii) cost-effectiveness of the intervention. We will enrol 500 participants over 2.5 years, with follow-up continuing until 12 months post-enrolment. Discussion: Our best TBM treatment still results in unacceptably high mortality and morbidity. Strong evidence supports the increased cerebrospinal fluid penetration of high dose rifampicin, however conclusive evidence regarding survival benefit is lacking. This study will answer the important question of whether high dose oral rifampicin conveys a survival benefit in TBM in HIV-positive and -negative individuals from Africa and Asia. Trial registration: ISRCTN15668391 (17/06/2019) Keywords: Tuberculous Meningitis, TB, rifampicin, Xpert Ultra, HIV, treatment, RCT |
Sanya, Richard E; Biraro, Irene Andia; Nampijja, Margaret; Zziwa, Christopher; Nanyunja, Carol; Nsubuga, Denis; Kiwanuka, Samuel; Tumusiime, Josephine; Nassuuna, Jacent; Walusimbi, Bridgious; Cose, Stephen; Ocama, Ponsiano; Grencis, Richard K; Elliott, Alison M; Webb, Emily L Contrasting impact of rural, versus urban, living on glucose metabolism and blood pressure in Uganda Journal Article Wellcome Open Research, 5 (1), pp. 39, 2020. @article{Sanya2020, title = {Contrasting impact of rural, versus urban, living on glucose metabolism and blood pressure in Uganda}, author = {Richard E. Sanya and Irene Andia Biraro and Margaret Nampijja and Christopher Zziwa and Carol Nanyunja and Denis Nsubuga and Samuel Kiwanuka and Josephine Tumusiime and Jacent Nassuuna and Bridgious Walusimbi and Stephen Cose and Ponsiano Ocama and Richard K. Grencis and Alison M. Elliott and Emily L. Webb}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447960/}, doi = { doi: 10.12688/wellcomeopenres.15616.2}, year = {2020}, date = {2020-08-24}, journal = {Wellcome Open Research}, volume = {5}, number = {1}, pages = {39}, abstract = {Abstract Background: The burden of cardiometabolic diseases, including cardiovascular diseases and diabetes, is increasing in sub-Saharan Africa and this has been linked to urbanisation. Helminths, through their immunomodulatory properties, may protect against these disorders. We hypothesised that the rural environment protects against cardiometabolic diseases and that helminths may influence rural-urban disparity of cardiometabolic disease risk. Methods: We compared metabolic parameters of individuals aged ≥10 years living in rural, high-helminth-transmission and urban, lower-helminth-transmission settings in Uganda. Cross-sectional surveys were conducted in rural Lake Victoria island fishing communities and in urban sub-wards in Entebbe municipality. Helminth infection and outcomes, including insulin resistance (computed using the homeostatic model assessment of insulin resistance [HOMA-IR]), fasting blood glucose, fasting blood lipids, blood pressure, body mass index (BMI), waist and hip circumference, were assessed. Results: We analysed 1,898 rural and 930 urban participants. Adjusting for BMI, exercise, smoking, alcohol intake, age and sex, urban residents had lower mean fasting glucose (adjusted mean difference [95%CI] 0.18 [-0.32, -0.05] p=0.01) and HOMA-IR (-0.26 [-0.40, -0.11] p=0.001) but higher blood pressure (systolic, 5.45 [3.75, 7.15] p<0.001; diastolic, 1.93 [0.57, 3.29] p=0.006). Current helminth infection did not explain the observed differences. Conclusions: In the Ugandan context, living in rural fishing communities may protect against hypertension but worsen glucose metabolism. Keywords: Rural, Urban, Metabolic, Hypertension, Diabetes, Insulin resistance, Helminths, Africa}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: The burden of cardiometabolic diseases, including cardiovascular diseases and diabetes, is increasing in sub-Saharan Africa and this has been linked to urbanisation. Helminths, through their immunomodulatory properties, may protect against these disorders. We hypothesised that the rural environment protects against cardiometabolic diseases and that helminths may influence rural-urban disparity of cardiometabolic disease risk. Methods: We compared metabolic parameters of individuals aged ≥10 years living in rural, high-helminth-transmission and urban, lower-helminth-transmission settings in Uganda. Cross-sectional surveys were conducted in rural Lake Victoria island fishing communities and in urban sub-wards in Entebbe municipality. Helminth infection and outcomes, including insulin resistance (computed using the homeostatic model assessment of insulin resistance [HOMA-IR]), fasting blood glucose, fasting blood lipids, blood pressure, body mass index (BMI), waist and hip circumference, were assessed. Results: We analysed 1,898 rural and 930 urban participants. Adjusting for BMI, exercise, smoking, alcohol intake, age and sex, urban residents had lower mean fasting glucose (adjusted mean difference [95%CI] 0.18 [-0.32, -0.05] p=0.01) and HOMA-IR (-0.26 [-0.40, -0.11] p=0.001) but higher blood pressure (systolic, 5.45 [3.75, 7.15] p<0.001; diastolic, 1.93 [0.57, 3.29] p=0.006). Current helminth infection did not explain the observed differences. Conclusions: In the Ugandan context, living in rural fishing communities may protect against hypertension but worsen glucose metabolism. Keywords: Rural, Urban, Metabolic, Hypertension, Diabetes, Insulin resistance, Helminths, Africa |
Sebatta, Deborah Ekusai; Siu, Godfrey; Nabeta, Henry W; Anguzu, Godwin; Walimbwa, Stephen; Lamorde, Mohammed; Bukenya, Badru; Kambugu, Andrew BMC Medical Ethics, 21 (1), pp. 77, 2020. @article{Sebatta2020, title = {“You would not be in a hurry to go back home”: patients’ willingness to participate in HIV/AIDS clinical trials at a clinical and research facility in Kampala, Uganda}, author = {Deborah Ekusai Sebatta and Godfrey Siu and Henry W. Nabeta and Godwin Anguzu and Stephen Walimbwa and Mohammed Lamorde and Badru Bukenya and Andrew Kambugu }, url = {https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-020-00516-z}, doi = {https://doi.org/10.1186/s12910-020-00516-z}, year = {2020}, date = {2020-08-24}, journal = {BMC Medical Ethics}, volume = {21}, number = {1}, pages = {77}, abstract = {Abstract Background Few studies have examined factors associated with willingness of people living with HIV (PLHIV) to participate in HIV treatment clinical trials in Sub-Saharan Africa. We assessed the factors associated with participation of PLHIV in HIV treatment clinical trials research at a large urban clinical and research facility in Uganda. Methods A mixed methods study was conducted at the Infectious Diseases Institute (IDI), adult HIV clinic between July 2016 and January 2017. Data were collected using structured questionnaires, focused group discussions with respondents categorised as either participated or never participated in clinical trials and key informant interviews with IDI staff. A generalized linear model with a logit link function was used for multivariate analyses while the qualitative data were summarized using a thematic approach. Results We enrolled a total of 202 and analysed 151 participants, 77 (51%) of whom were male with mean age of 41 years. The majority 127 (84%) expressed willingness to participate in treatment clinical trials if given an opportunity. At bivariate analysis, willingness to participate was significantly associated with respondents’ perception of a satisfactory compensation package (P-value < 0.002, 0.08–0.56), special status accorded (P-value < 0.001, 0.05–0.39) and belief that their health status would improve (P-value< 0.08, 0.03–0.58) while on the clinical trial. At multivariate analysis, a satisfactory compensation package (P-value< 0.030, 0.08–0.88) and special status accorded in clinical trials (P-value< 0.041, 0.01–0.91) remained significant. The qualitative data analysis confirmed these findings as participants valued the privilege of jumping the clinic waiting queues and spending less time in clinic, the wide range of free tests offered to trial participants, unrestricted access to senior physicians and regular communication from study team. Additionally, free meals offered during clinic visits meant that participants were not in a hurry to go back home. Barriers to participation included the perception that new drugs were being tested on them, fear of side effects like treatment failure and the uncertainty about privacy of their data. Conclusion We found overwhelming willingness to participate in HIV treatment clinical trials. This was largely extrinsically influenced by the perceived material and health-related benefits. Investigators should pay attention to participants’ concerns for benefits which may override the need to understand study procedures and risks.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Few studies have examined factors associated with willingness of people living with HIV (PLHIV) to participate in HIV treatment clinical trials in Sub-Saharan Africa. We assessed the factors associated with participation of PLHIV in HIV treatment clinical trials research at a large urban clinical and research facility in Uganda. Methods A mixed methods study was conducted at the Infectious Diseases Institute (IDI), adult HIV clinic between July 2016 and January 2017. Data were collected using structured questionnaires, focused group discussions with respondents categorised as either participated or never participated in clinical trials and key informant interviews with IDI staff. A generalized linear model with a logit link function was used for multivariate analyses while the qualitative data were summarized using a thematic approach. Results We enrolled a total of 202 and analysed 151 participants, 77 (51%) of whom were male with mean age of 41 years. The majority 127 (84%) expressed willingness to participate in treatment clinical trials if given an opportunity. At bivariate analysis, willingness to participate was significantly associated with respondents’ perception of a satisfactory compensation package (P-value < 0.002, 0.08–0.56), special status accorded (P-value < 0.001, 0.05–0.39) and belief that their health status would improve (P-value< 0.08, 0.03–0.58) while on the clinical trial. At multivariate analysis, a satisfactory compensation package (P-value< 0.030, 0.08–0.88) and special status accorded in clinical trials (P-value< 0.041, 0.01–0.91) remained significant. The qualitative data analysis confirmed these findings as participants valued the privilege of jumping the clinic waiting queues and spending less time in clinic, the wide range of free tests offered to trial participants, unrestricted access to senior physicians and regular communication from study team. Additionally, free meals offered during clinic visits meant that participants were not in a hurry to go back home. Barriers to participation included the perception that new drugs were being tested on them, fear of side effects like treatment failure and the uncertainty about privacy of their data. Conclusion We found overwhelming willingness to participate in HIV treatment clinical trials. This was largely extrinsically influenced by the perceived material and health-related benefits. Investigators should pay attention to participants’ concerns for benefits which may override the need to understand study procedures and risks. |
Kwizera, Richard; Sadiq, Alisat; Ndyetukira, Jane Frances; Nalintya, Elizabeth; Williams, Darlisha; Rhein, Joshua; Boulware, David R; for the COAT, David Meya B; trial teams, ASTRO Impact of community engagement and social support on the outcomes of HIV-related meningitis clinical trials in a resource-limited setting Journal Article Research Involvement and Engagement, 6 (1), pp. 49, 2020. @article{Kwizera2020e, title = {Impact of community engagement and social support on the outcomes of HIV-related meningitis clinical trials in a resource-limited setting}, author = {Richard Kwizera and Alisat Sadiq and Jane Frances Ndyetukira and Elizabeth Nalintya and Darlisha Williams and Joshua Rhein and David R. Boulware and David B. Meya for the COAT and ASTRO trial teams}, url = {https://researchinvolvement.biomedcentral.com/articles/10.1186/s40900-020-00228-z}, doi = {https://doi.org/10.1186/s40900-020-00228-z}, year = {2020}, date = {2020-08-20}, journal = {Research Involvement and Engagement}, volume = {6}, number = {1}, pages = {49}, abstract = {Abstract Background Clinical trials remain the cornerstone of improving outcomes for HIV-infected individuals with cryptococcal meningitis. Community engagement aims at involving participants and their advocates as partners in research rather than merely trial subjects. Community engagement can help to build trust in communities where these trials are conducted and ensure lasting mutually beneficial relationships between researchers and the community. Similarly, different studies have reported the positive effects of social support on patient’s outcomes. We aimed to describe our approach to community engagement in Uganda while highlighting the benefits of community engagement and social support in clinical trials managing patients co-infected with HIV and cryptococcal meningitis. Methods We carried out community engagement using home visits, health talks, posters, music and drama. In addition, social support was given through study staff individually contributing to provide funds for participants’ food, wheel chairs, imaging studies, adult diapers, and other extra investigations or drugs that were not covered by the study budget or protocol. The benefits of this community engagement and social support were assessed during two multi-site, randomized cryptococcal meningitis clinical trials in Uganda. Results We screened 1739 HIV-infected adults and enrolled 934 with cryptococcal meningitis into the COAT and ASTRO-CM trials during the period October 2010 to July 2017. Lumbar puncture refusal rates decreased from 31% in 2010 to less than 1% in 2017. In our opinion, community engagement and social support played an important role in improving: drug adherence, acceptance of lumbar punctures, data completeness, rate of screening/referrals, reduction of missed visits, and loss to follow-up. Conclusions Community engagement and social support are important aspects of clinical research and should be incorporated into clinical trial design and conduct.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Clinical trials remain the cornerstone of improving outcomes for HIV-infected individuals with cryptococcal meningitis. Community engagement aims at involving participants and their advocates as partners in research rather than merely trial subjects. Community engagement can help to build trust in communities where these trials are conducted and ensure lasting mutually beneficial relationships between researchers and the community. Similarly, different studies have reported the positive effects of social support on patient’s outcomes. We aimed to describe our approach to community engagement in Uganda while highlighting the benefits of community engagement and social support in clinical trials managing patients co-infected with HIV and cryptococcal meningitis. Methods We carried out community engagement using home visits, health talks, posters, music and drama. In addition, social support was given through study staff individually contributing to provide funds for participants’ food, wheel chairs, imaging studies, adult diapers, and other extra investigations or drugs that were not covered by the study budget or protocol. The benefits of this community engagement and social support were assessed during two multi-site, randomized cryptococcal meningitis clinical trials in Uganda. Results We screened 1739 HIV-infected adults and enrolled 934 with cryptococcal meningitis into the COAT and ASTRO-CM trials during the period October 2010 to July 2017. Lumbar puncture refusal rates decreased from 31% in 2010 to less than 1% in 2017. In our opinion, community engagement and social support played an important role in improving: drug adherence, acceptance of lumbar punctures, data completeness, rate of screening/referrals, reduction of missed visits, and loss to follow-up. Conclusions Community engagement and social support are important aspects of clinical research and should be incorporated into clinical trial design and conduct. |
Nakanjako, Damalie; Zalwango, Flavia; Wairagala, Pamela; Luboga, Fiona; Biraro, Irene Andia; Bukirwa, Victoria Diana; Mboowa, Mary Gorrethy; Cose, Steve; Seeley, Janet; Elliott, Alison AAS Open Research, 3 , pp. 26, 2020. @article{Nakanjako2020, title = {Career development for infection and immunity research in Uganda: a decade of experience from the Makerere University – Uganda Virus Research Institute research and training programme}, author = {Damalie Nakanjako and Flavia Zalwango and Pamela Wairagala and Fiona Luboga and Irene Andia Biraro and Victoria Diana Bukirwa and Mary Gorrethy Mboowa and Steve Cose and Janet Seeley and Alison Elliott}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372530.2/}, doi = {doi: 10.12688/aasopenres.13066.2}, year = {2020}, date = {2020-08-17}, journal = {AAS Open Research}, volume = {3}, pages = {26}, abstract = {Abstract Background: The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII’s achievements, challenges and lessons learned between 08-2008 and 12-2019, to inform programmes seeking to build Africa’s health research expertise. Methods: Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in 03-04/2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. Results: By 12-2019, MUII had supported 68 fellowships at master’s-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leaders) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons were: i) Efficient administration provides a conducive environment for high quality research; ii) Institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; iii) Strong international and multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and iv) Mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society’s most pressing health challenges. Conclusions: Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa’s health challenges. Keywords: Academic careers, capacity building for research, Infection and Immunity, Immunology, bioinformatics, mentorship, collaboration, partnership, sub-Saharan Africa}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII’s achievements, challenges and lessons learned between 08-2008 and 12-2019, to inform programmes seeking to build Africa’s health research expertise. Methods: Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in 03-04/2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. Results: By 12-2019, MUII had supported 68 fellowships at master’s-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leaders) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons were: i) Efficient administration provides a conducive environment for high quality research; ii) Institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; iii) Strong international and multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and iv) Mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society’s most pressing health challenges. Conclusions: Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa’s health challenges. Keywords: Academic careers, capacity building for research, Infection and Immunity, Immunology, bioinformatics, mentorship, collaboration, partnership, sub-Saharan Africa |
Kasibante, John; Rutakingirwa, Morris K; Kagimu, Enock; Ssebambulidde, Kenneth; Ellisa, Jayne; LillianTugume, ; Mpoza, Edward; Cresswell, Fiona; Meya, David B Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 20 , 2020. @article{Kasibante2020, title = {Tuberculosis preventive therapy (TPT) to prevent tuberculosis co-infection among adults with HIV-associated cryptococcal meningitis: A clinician's }, author = {John Kasibante and Morris K. Rutakingirwa and Enock Kagimu and Kenneth Ssebambulidde and Jayne Ellisa and LillianTugume and Edward Mpoza and Fiona Cresswell and David B. Meya}, url = {https://www.sciencedirect.com/science/article/pii/S2405579420300449}, doi = {https://doi.org/10.1016/j.jctube.2020.100180}, year = {2020}, date = {2020-08-13}, journal = {Journal of Clinical Tuberculosis and Other Mycobacterial Diseases}, volume = {20}, abstract = {Abstract As part of the END TB strategy, the World Health organization (WHO) recommends provision of tuberculosis preventive therapy (TPT) to all people at high risk of developing active TB disease. Patients with HIV-associated cryptococcal meningitis are severely immunocompromised and therefore should be eligible for TPT. In this commentary we discuss the challenges associated with starting tuberculosis preventive therapy in patients with HIV associated cryptococcal meningitis in a clinical setting, we highlight the benefit, existing gaps and research opportunities of tuberculosis preventive therapy in this patient population.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract As part of the END TB strategy, the World Health organization (WHO) recommends provision of tuberculosis preventive therapy (TPT) to all people at high risk of developing active TB disease. Patients with HIV-associated cryptococcal meningitis are severely immunocompromised and therefore should be eligible for TPT. In this commentary we discuss the challenges associated with starting tuberculosis preventive therapy in patients with HIV associated cryptococcal meningitis in a clinical setting, we highlight the benefit, existing gaps and research opportunities of tuberculosis preventive therapy in this patient population. |
Baluku, Joseph Baruch; Anguzu, Godwin; Nassozi, Sylvia; Babirye, Febronius; Namiiro, Sharon; Buyungo, Robert; Sempiira, Mike; Wasswa, Amir; Mulwana, Rose; Ntambi, Samuel; Worodria, William; Andia-Biraro, Irene Prevalence of HIV infection and bacteriologically confirmed tuberculosis among individuals found at bars in Kampala slums, Uganda Journal Article Scientific Reports, 10 (1), pp. 13438, 2020. @article{Baluku2020b, title = {Prevalence of HIV infection and bacteriologically confirmed tuberculosis among individuals found at bars in Kampala slums, Uganda}, author = {Joseph Baruch Baluku and Godwin Anguzu and Sylvia Nassozi and Febronius Babirye and Sharon Namiiro and Robert Buyungo and Mike Sempiira and Amir Wasswa and Rose Mulwana and Samuel Ntambi and William Worodria and Irene Andia-Biraro }, url = {https://www.nature.com/articles/s41598-020-70472-6}, doi = {https://doi.org/10.1038/s41598-020-70472-6}, year = {2020}, date = {2020-08-10}, journal = {Scientific Reports}, volume = {10}, number = {1}, pages = {13438}, abstract = {Abstract Individuals found at bars in slums have several risk factors for HIV and tuberculosis (TB). To determine the prevalence of HIV and TB among individuals found at bars in slums of Kampala, Uganda, we enrolled adults found at bars that provided written informed consent. Individuals with alcohol intoxication were excluded. We performed HIV testing using immunochromatographic antibody tests (Alere Determine HIV-1/2 and Chembio HIV 1/2 STAT-PAK). TB was confirmed using the Xpert MTB/RIF Ultra assay, performed on single spot sputum samples. We enrolled 272 participants from 42 bars in 5 slums. The prevalence of HIV and TB was 11.4% (95% CI 8.1–15.8) and 15 (95% CI 6–39) per 1,000 population respectively. Predictors of HIV were female sex (aOR 5.87, 95% CI 2.05–16.83), current cigarette smoking (aOR 3.23, 95% CI 1.02–10.26), history of TB treatment (aOR 10.19, 95% CI 3.17–32.82) and CAGE scores of 2–3 (aOR 3.90, 95% CI 1.11–13.70) and 4 (aOR 4.77, 95% CI 1.07–21.35). The prevalence of HIV and TB was twice and four times the national averages respectively. These findings highlight the need for concurrent programmatic screening for both HIV and TB among high risk populations in slums.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Individuals found at bars in slums have several risk factors for HIV and tuberculosis (TB). To determine the prevalence of HIV and TB among individuals found at bars in slums of Kampala, Uganda, we enrolled adults found at bars that provided written informed consent. Individuals with alcohol intoxication were excluded. We performed HIV testing using immunochromatographic antibody tests (Alere Determine HIV-1/2 and Chembio HIV 1/2 STAT-PAK). TB was confirmed using the Xpert MTB/RIF Ultra assay, performed on single spot sputum samples. We enrolled 272 participants from 42 bars in 5 slums. The prevalence of HIV and TB was 11.4% (95% CI 8.1–15.8) and 15 (95% CI 6–39) per 1,000 population respectively. Predictors of HIV were female sex (aOR 5.87, 95% CI 2.05–16.83), current cigarette smoking (aOR 3.23, 95% CI 1.02–10.26), history of TB treatment (aOR 10.19, 95% CI 3.17–32.82) and CAGE scores of 2–3 (aOR 3.90, 95% CI 1.11–13.70) and 4 (aOR 4.77, 95% CI 1.07–21.35). The prevalence of HIV and TB was twice and four times the national averages respectively. These findings highlight the need for concurrent programmatic screening for both HIV and TB among high risk populations in slums. |
Eneh, Prosperity C; Hullsiek, Katherine Huppler; Kiiza, Daniel; Rhein, Joshua; Meya, David B; Boulware, David R; Nicol, Melanie R Prevalence and nature of potential drug-drug interactions among hospitalized HIV patients presenting with suspected meningitis in Uganda Journal Article BMC Infectious Diseases, 20 (1), pp. 572, 2020. @article{Eneh2020, title = {Prevalence and nature of potential drug-drug interactions among hospitalized HIV patients presenting with suspected meningitis in Uganda}, author = {Prosperity C. Eneh and Katherine Huppler Hullsiek and Daniel Kiiza and Joshua Rhein and David B. Meya and David R. Boulware and Melanie R. Nicol }, url = {https://link.springer.com/article/10.1186/s12879-020-05296-w}, doi = {https://doi.org/10.1186/s12879-020-05296-w}, year = {2020}, date = {2020-08-05}, journal = {BMC Infectious Diseases}, volume = {20}, number = {1}, pages = {572}, abstract = {Abstract Background Management of co-infections including cryptococcal meningitis, tuberculosis and other opportunistic infections in persons living with HIV can lead to complex polypharmacotherapy and increased susceptibility to drug-drug interactions (DDIs). Here we characterize the frequency and types of potential DDIs (pDDIs) in hospitalized HIV patients presenting with suspected cryptococcal or tuberculous meningitis. Methods In a retrospective review of three cryptococcal meningitis trials between 2010 and 2017 in Kampala, Uganda, medications received over hospitalization were documented and pDDI events were assessed. IBM Micromedex DRUGDEX® online drug reference system was used to identify and describe potential interactions as either contraindicated, major, moderate or minor. For antiretroviral DDIs, the Liverpool Drug Interactions Checker from the University of Liverpool was also used to further describe interactions observed. Results In 1074 patients with suspected meningitis, pDDIs were present in 959 (overall prevalence = 89.3%) during the analyzed 30 day window. In total, 278 unique interacting drug pairs were identified resulting in 4582 pDDI events. Of all patients included in this study there was a mean frequency of 4.27 pDDIs per patient. Of the 4582 pDDI events, 11.3% contraindicated, 66.4% major, 17.4% moderate and 5% minor pDDIs were observed. Among all pDDIs identified, the most prevalent drugs implicated were fluconazole (58.4%), co-trimoxazole (25.7%), efavirenz (15.6%) and rifampin (10.2%). Twenty-one percent of the contraindicated pDDIs and 27% of the major ones involved an antiretroviral drug. Increased likelihood of QT interval prolongation was the most frequent potential clinical outcome. Dissonance in drug interaction checkers was noted requiring clinicians to consult more than one database in making clinical decisions about drug combinations. Conclusions The overall prevalence of pDDIs in this population is high. An understanding of drug combinations likely to result in undesired clinical outcomes, such as QT interval prolongation, is paramount. This is especially important in resource limited settings where availability of therapeutic drug monitoring and laboratory follow-up are inconsistent. Adequate quantification of the increased likelihood of adverse clinical outcomes from multiple drug-drug interactions of the same kind in a single patient is needed to aid clinical decisions in this setting. Key findings The result of this analysis shows that potential drug-drug interactions, ranging from minor to contradicted interactions, in this subset of the population are significant and sometimes unavoidable. Although frequency and type of drug-drug interactions have been previously characterized in various populations, this is to our knowledge the first description of potential drug-drug interactions among hospitalized patients living with HIV and presenting with co-morbidities like meningitis and tuberculosis. The findings will be of particular interest to clinicians in similar settings as this information can inform their monitoring and care of these patients especially given the vulnerabilities they face due to their comorbidities.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Management of co-infections including cryptococcal meningitis, tuberculosis and other opportunistic infections in persons living with HIV can lead to complex polypharmacotherapy and increased susceptibility to drug-drug interactions (DDIs). Here we characterize the frequency and types of potential DDIs (pDDIs) in hospitalized HIV patients presenting with suspected cryptococcal or tuberculous meningitis. Methods In a retrospective review of three cryptococcal meningitis trials between 2010 and 2017 in Kampala, Uganda, medications received over hospitalization were documented and pDDI events were assessed. IBM Micromedex DRUGDEX® online drug reference system was used to identify and describe potential interactions as either contraindicated, major, moderate or minor. For antiretroviral DDIs, the Liverpool Drug Interactions Checker from the University of Liverpool was also used to further describe interactions observed. Results In 1074 patients with suspected meningitis, pDDIs were present in 959 (overall prevalence = 89.3%) during the analyzed 30 day window. In total, 278 unique interacting drug pairs were identified resulting in 4582 pDDI events. Of all patients included in this study there was a mean frequency of 4.27 pDDIs per patient. Of the 4582 pDDI events, 11.3% contraindicated, 66.4% major, 17.4% moderate and 5% minor pDDIs were observed. Among all pDDIs identified, the most prevalent drugs implicated were fluconazole (58.4%), co-trimoxazole (25.7%), efavirenz (15.6%) and rifampin (10.2%). Twenty-one percent of the contraindicated pDDIs and 27% of the major ones involved an antiretroviral drug. Increased likelihood of QT interval prolongation was the most frequent potential clinical outcome. Dissonance in drug interaction checkers was noted requiring clinicians to consult more than one database in making clinical decisions about drug combinations. Conclusions The overall prevalence of pDDIs in this population is high. An understanding of drug combinations likely to result in undesired clinical outcomes, such as QT interval prolongation, is paramount. This is especially important in resource limited settings where availability of therapeutic drug monitoring and laboratory follow-up are inconsistent. Adequate quantification of the increased likelihood of adverse clinical outcomes from multiple drug-drug interactions of the same kind in a single patient is needed to aid clinical decisions in this setting. Key findings The result of this analysis shows that potential drug-drug interactions, ranging from minor to contradicted interactions, in this subset of the population are significant and sometimes unavoidable. Although frequency and type of drug-drug interactions have been previously characterized in various populations, this is to our knowledge the first description of potential drug-drug interactions among hospitalized patients living with HIV and presenting with co-morbidities like meningitis and tuberculosis. The findings will be of particular interest to clinicians in similar settings as this information can inform their monitoring and care of these patients especially given the vulnerabilities they face due to their comorbidities. |
Pintye, Jillian; Davey, Dvora Joseph L; Wagner, Anjuli D; John-Stewart, Grace; Baggaley, Rachel; Bekker, Linda-Gail; Celum, Connie; Benjamin, ; Coates, Thomas J; Groves, Allison K; Haberer, Jessica E; Heffron, Renee; Kinuthia, John; Matthews, Lynn T; McIntyre, James A; Moodley, Dhayendre; Mofenson, Lynne M; Mugo, Nelly; Mujugira, Andrew; Myer, Landon; Shoptaw, Steven; Stranix-Chibanda, Lynda; Baeten, Jared M; for the in Group, PrEP Pregnancy Working The Lancet HIV, 7 (8), pp. e582-e592, 2020. @article{Pintye2020, title = {Defining gaps in pre-exposure prophylaxis delivery for pregnant and post-partum women in high-burden settings using an implementation science framework}, author = {Jillian Pintye and Dvora L Joseph Davey and Anjuli D Wagner and Grace John-Stewart and Rachel Baggaley and Linda-Gail Bekker and Connie Celum and Benjamin and Thomas J Coates and Allison K Groves and Jessica E Haberer and Renee Heffron and John Kinuthia and Lynn T Matthews and James A McIntyre and Dhayendre Moodley and Lynne M Mofenson and Nelly Mugo and Andrew Mujugira and Landon Myer and Steven Shoptaw and Lynda Stranix-Chibanda and Jared M Baeten and for the PrEP in Pregnancy Working Group}, url = {https://www.sciencedirect.com/science/article/abs/pii/S2352301820301028}, doi = {https://doi.org/10.1016/S2352-3018(20)30102-8}, year = {2020}, date = {2020-08-04}, journal = {The Lancet HIV}, volume = {7}, number = {8}, pages = {e582-e592}, abstract = {Summary Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Summary Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context. |
Muhindo, Richard; Mujugira, Andrew; Castelnuovo, Barbara; Sewankambo, Nelson K; Parkes-Ratanshi, Rosalind; Kiguli, Juliet; Tumwesigye, Nazarius Mbona; Nakku-Joloba, Edith HIV and syphilis testing behaviors among heterosexual male and female sex workers in Uganda Journal Article AIDS Research and Therapy, 17 (1), pp. 48, 2020. @article{Muhindo2020, title = {HIV and syphilis testing behaviors among heterosexual male and female sex workers in Uganda}, author = {Richard Muhindo and Andrew Mujugira and Barbara Castelnuovo and Nelson K. Sewankambo and Rosalind Parkes-Ratanshi and Juliet Kiguli and Nazarius Mbona Tumwesigye and Edith Nakku-Joloba }, url = {https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-020-00306-y}, doi = {https://doi.org/10.1186/s12981-020-00306-y}, year = {2020}, date = {2020-08-01}, journal = {AIDS Research and Therapy}, volume = {17}, number = {1}, pages = {48}, abstract = {Abstract Background In Sub-Saharan Africa where HIV disproportionately affects women, heterosexual male sex workers (HMSW) and their female clients are at risk of acquiring or transmitting HIV and other STIs. However, few studies have described HIV and STI risk among HMSW. We aimed to assess and compare recent HIV and syphilis screening practices among HMSW and female sex workers (FSW) in Uganda. Methods Between August and December 2019, we conducted a cross-sectional study among 100 HMSW and 240 female sex workers (FSW). Participants were enrolled through snowball sampling, and an interviewer-administered questionnaire used to collect data on HIV and syphilis testing in the prior 12 and 6 months respectively. Integrated change model constructs were used to assess intentions, attitudes, social influences, norms and self-efficacy of 3-monthly Syphilis and 6-monthly HIV testing. Predictors of HIV and syphilis recent testing behaviors were estimated using negative binomial regression. Results We enrolled 340 sex workers of whom 100 (29%) were HMSW. The median age was 27 years [interquartile range (IQR) 25–30] for HMSW and 26 years [IQR], (23–29) for FSW. The median duration of sex work was 36 and 30 months for HMSW and FSW, respectively. HMSW were significantly less likely than FSW to have tested for HIV in the prior 12 months (50% vs. 86%; p = 0.001). For MSW, non-testing for HIV was associated with higher education [adjusted prevalence ratio (aPR) 1.66; 95% confidence interval (CI) 1.09–2.50], poor intention to seek HIV testing (aPR 1.64; 95% CI 1.35–2.04), perception that 6-monthly HIV testing was not normative (aPR 1.33; 95% CI 1.09–1.67) and low self-efficacy (aPR 1.41; 95% CI 1.12–1.79). Not testing for syphilis was associated with low intention to seek testing (aPR 3.13; 95% CI 2.13–4.55), low self-efficacy (aPR 2.56; 95% CI 1.35–4.76), negative testing attitudes (aPR 2.33; 95% CI 1.64–3.33), and perception that regular testing was not normative (aPR 1.59; 95% CI 1.14–2.22). Conclusions Non-testing for HIV and syphilis was common among HMSW relative to FSW. Future studies should evaluate strategies to increase testing uptake for this neglected sub-population of sex workers.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background In Sub-Saharan Africa where HIV disproportionately affects women, heterosexual male sex workers (HMSW) and their female clients are at risk of acquiring or transmitting HIV and other STIs. However, few studies have described HIV and STI risk among HMSW. We aimed to assess and compare recent HIV and syphilis screening practices among HMSW and female sex workers (FSW) in Uganda. Methods Between August and December 2019, we conducted a cross-sectional study among 100 HMSW and 240 female sex workers (FSW). Participants were enrolled through snowball sampling, and an interviewer-administered questionnaire used to collect data on HIV and syphilis testing in the prior 12 and 6 months respectively. Integrated change model constructs were used to assess intentions, attitudes, social influences, norms and self-efficacy of 3-monthly Syphilis and 6-monthly HIV testing. Predictors of HIV and syphilis recent testing behaviors were estimated using negative binomial regression. Results We enrolled 340 sex workers of whom 100 (29%) were HMSW. The median age was 27 years [interquartile range (IQR) 25–30] for HMSW and 26 years [IQR], (23–29) for FSW. The median duration of sex work was 36 and 30 months for HMSW and FSW, respectively. HMSW were significantly less likely than FSW to have tested for HIV in the prior 12 months (50% vs. 86%; p = 0.001). For MSW, non-testing for HIV was associated with higher education [adjusted prevalence ratio (aPR) 1.66; 95% confidence interval (CI) 1.09–2.50], poor intention to seek HIV testing (aPR 1.64; 95% CI 1.35–2.04), perception that 6-monthly HIV testing was not normative (aPR 1.33; 95% CI 1.09–1.67) and low self-efficacy (aPR 1.41; 95% CI 1.12–1.79). Not testing for syphilis was associated with low intention to seek testing (aPR 3.13; 95% CI 2.13–4.55), low self-efficacy (aPR 2.56; 95% CI 1.35–4.76), negative testing attitudes (aPR 2.33; 95% CI 1.64–3.33), and perception that regular testing was not normative (aPR 1.59; 95% CI 1.14–2.22). Conclusions Non-testing for HIV and syphilis was common among HMSW relative to FSW. Future studies should evaluate strategies to increase testing uptake for this neglected sub-population of sex workers. |
Alhassan, Yussif; Twimukye, Adelline; Malaba, Thoko; Orrell, Catherine; Myer, Landon; Waitt, Catriona; Lamorde, Mohammed; Kambugu, Andrew; Reynolds, Helen; Khoo, Saye; Taegtmeyer, Miriam BMC Health Services Research, 20 (1), pp. 705, 2020. @article{Alhassan2020, title = {Engendering health systems in response to national rollout of dolutegravir-based regimens among women of childbearing potential: a qualitative study with stakeholders in South Africa and Uganda}, author = {Yussif Alhassan and Adelline Twimukye and Thoko Malaba and Catherine Orrell and Landon Myer and Catriona Waitt and Mohammed Lamorde and Andrew Kambugu and Helen Reynolds and Saye Khoo and Miriam Taegtmeyer }, url = {https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-020-05580-0}, doi = {https://doi.org/10.1186/s12913-020-05580-0}, year = {2020}, date = {2020-08-01}, journal = {BMC Health Services Research}, volume = {20}, number = {1}, pages = {705}, abstract = {Abstract Background In the era of rapid dolutegravir rollout, concerns about neural tube defects have complicated the health systems response among women of childbearing potential. This qualitative study, which was nested within the DolPHIN-2 clinical trial, examined the current and future health system opportunities and challenges associated with the transition to dolutegravir-based regimen as first line antiretroviral therapy among women of childbearing potential in South Africa and Uganda. Method Semi-structured in-depth interviews with members of antiretroviral therapy guideline development groups and affiliates were conducted. Thirty-one participants were purposively selected for the study, including senior officials from the Ministry of Health and National Drug Regulatory Authority in Uganda and South Africa as well as health-sector development partners, activists, researchers and health workers. A thematic approach was used to analyse the data. Findings Despite differences in health system contexts, several common challenges and opportunities were identified with the transition among women of childbearing potential in South Africa and Uganda. In both contexts national stakeholders identified challenges with ensuring gender equity in roll out due to the potential teratogenicity of dolutegravir, paucity of data on dolutegravir use in pregnancy, potential stock out of effective contraceptives, poorly integrated contraception services, and limited pharmacovigilance in pregnancy. Participants identified opportunities that could be harnessed to accelerate the transition, including high stakeholder interest and commitment to transition, national approval and licensure of a generic tenofovir/lamivudine/dolutegravir regimen, availability of a network of antiretroviral therapy providers, and strong desire among women for newer and more tolerable regimens. Conclusion The transition to dolutegravir-based regimens has the potential to strengthen health systems in low- and middle-income countries to engender equitable access to optimised antiretroviral regimen among women. There is the need for a multi-sectoral effort to harness the opportunities of the health systems to addresses the bottlenecks to the transition and initiate extensive community engagement alongside individual and institutional capacity strengthening. Improvements in pregnancy pharmacovigilance and counselling and family planning services are critical to ensuring a successful transition among women of childbearing potential.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background In the era of rapid dolutegravir rollout, concerns about neural tube defects have complicated the health systems response among women of childbearing potential. This qualitative study, which was nested within the DolPHIN-2 clinical trial, examined the current and future health system opportunities and challenges associated with the transition to dolutegravir-based regimen as first line antiretroviral therapy among women of childbearing potential in South Africa and Uganda. Method Semi-structured in-depth interviews with members of antiretroviral therapy guideline development groups and affiliates were conducted. Thirty-one participants were purposively selected for the study, including senior officials from the Ministry of Health and National Drug Regulatory Authority in Uganda and South Africa as well as health-sector development partners, activists, researchers and health workers. A thematic approach was used to analyse the data. Findings Despite differences in health system contexts, several common challenges and opportunities were identified with the transition among women of childbearing potential in South Africa and Uganda. In both contexts national stakeholders identified challenges with ensuring gender equity in roll out due to the potential teratogenicity of dolutegravir, paucity of data on dolutegravir use in pregnancy, potential stock out of effective contraceptives, poorly integrated contraception services, and limited pharmacovigilance in pregnancy. Participants identified opportunities that could be harnessed to accelerate the transition, including high stakeholder interest and commitment to transition, national approval and licensure of a generic tenofovir/lamivudine/dolutegravir regimen, availability of a network of antiretroviral therapy providers, and strong desire among women for newer and more tolerable regimens. Conclusion The transition to dolutegravir-based regimens has the potential to strengthen health systems in low- and middle-income countries to engender equitable access to optimised antiretroviral regimen among women. There is the need for a multi-sectoral effort to harness the opportunities of the health systems to addresses the bottlenecks to the transition and initiate extensive community engagement alongside individual and institutional capacity strengthening. Improvements in pregnancy pharmacovigilance and counselling and family planning services are critical to ensuring a successful transition among women of childbearing potential. |
Skipper, Caleb; Schleiss, Mark R; Bangdiwala, Ananta S; Hernandez-Alvarado, Nelmary; Taseera, Kabanda; Nabeta, Henry W; Musubire, Abdu K; Lofgren, Sarah M; Wiesner, Darin L; Rhein, Joshua; Rajasingham, Radha; Schutz, Charlotte; Meintjes, Graeme; Muzoora, Conrad; Meya, David B; Boulware, David R; the Team., Cryptococcal Optimal Antiretroviral Therapy Timing (COAT) Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa Journal Article Clinical Infectious Diseases, 71 (3), pp. 525–531, 2020. @article{Skipper2020c, title = {Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa }, author = {Caleb Skipper and Mark R Schleiss and Ananta S Bangdiwala and Nelmary Hernandez-Alvarado and Kabanda Taseera and Henry W Nabeta and Abdu K Musubire and Sarah M Lofgren and Darin L Wiesner and Joshua Rhein and Radha Rajasingham and Charlotte Schutz and Graeme Meintjes and Conrad Muzoora and David B Meya and David R Boulware and the Cryptococcal Optimal Antiretroviral Therapy Timing (COAT) Team.}, url = {https://academic.oup.com/cid/article-abstract/71/3/525/5557865}, doi = {https://doi.org/10.1093/cid/ciz864}, year = {2020}, date = {2020-08-01}, journal = {Clinical Infectious Diseases}, volume = {71}, number = {3}, pages = {525–531}, abstract = {Abstract Background Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. Methods We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Results Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259–2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9–70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07–4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49–7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Conclusions Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). Clinical Trials Registration NCT01075152. Topic: hiv acquired immunodeficiency syndrome cryptococcal meningitis viremia cryptococcus cytomegalovirus mortality }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. Methods We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Results Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259–2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9–70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07–4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49–7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Conclusions Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). Clinical Trials Registration NCT01075152. Topic: hiv acquired immunodeficiency syndrome cryptococcal meningitis viremia cryptococcus cytomegalovirus mortality |
Baluku, Joseph Baruch; Mugabe, Pallen; Mulwana, Rose; Nassozi, Sylvia; Katuramu, Richard; Worodria, William BioMed Research International, 2020. @article{Baluku2020, title = {High Prevalence of Rifampicin Resistance Associated with Rural Residence and Very Low Bacillary Load among TB/HIV-Coinfected Patients at the National Tuberculosis Treatment Center in Uganda}, author = {Joseph Baruch Baluku and Pallen Mugabe and Rose Mulwana and Sylvia Nassozi and Richard Katuramu and William Worodria}, url = {https://www.hindawi.com/journals/bmri/2020/2508283/}, doi = {https://doi.org/10.1155/2020/2508283}, year = {2020}, date = {2020-07-25}, journal = {BioMed Research International}, abstract = {Abstract Background. Rifampicin resistance (RR) is associated with mortality among tuberculosis (TB) patients coinfected with HIV. We compared the prevalence of RR among TB patients with and without HIV coinfection at the National Tuberculosis Treatment Center (NTTC) in Uganda, a TB/HIV high burdened country. We further determined associations of RR among TB/HIV-coinfected patients. Methods. In this secondary analysis, we included adult (≥18 years) bacteriologically confirmed TB patients that were enrolled in a cross-sectional study at the NTTC in Uganda between August 2017 and March 2018. TB, RR, and bacillary load were confirmed by the Xpert® MTB/RIF assay in the primary study. A very low bacillary load was defined as a cycle threshold value of >28. We compared the prevalence of RR among TB patients with and without HIV coinfection using Pearson’s chi-square test. We performed logistic regression analysis to determine associations of RR among TB/HIV-coinfected patients. Results. Of the 303 patients, 182 (60.1%) were male, 111 (36.6%) had TB/HIV coinfection, and the median (interquartile range) age was 31 (25-39) years. RR was found among 58 (19.1%) patients. The prevalence of RR was 32.4% (36/111) (95% confidence interval (CI): 24-42) among TB/HIV-coinfected patients compared to 11.5% (22/192) (95% CI: 7–17) among HIV-negative TB patients ( ). Among TB/HIV-coinfected patients, those with RR were more likely to be rural residents (adjusted odds ratio (aOR): 5.24, 95% CI: 1.51–18.21, ) and have a very low bacillary load (aOR: 13.52, 95% CI: 3.15–58.08, ). Conclusion. There was a high prevalence of RR among TB/HIV-coinfected patients. RR was associated with rural residence and having a very low bacillary load among TB/HIV-coinfected patients. The findings highlight a need for universal access to drug susceptibility testing among TB/HIV-coinfected patients, especially in rural settings.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background. Rifampicin resistance (RR) is associated with mortality among tuberculosis (TB) patients coinfected with HIV. We compared the prevalence of RR among TB patients with and without HIV coinfection at the National Tuberculosis Treatment Center (NTTC) in Uganda, a TB/HIV high burdened country. We further determined associations of RR among TB/HIV-coinfected patients. Methods. In this secondary analysis, we included adult (≥18 years) bacteriologically confirmed TB patients that were enrolled in a cross-sectional study at the NTTC in Uganda between August 2017 and March 2018. TB, RR, and bacillary load were confirmed by the Xpert® MTB/RIF assay in the primary study. A very low bacillary load was defined as a cycle threshold value of >28. We compared the prevalence of RR among TB patients with and without HIV coinfection using Pearson’s chi-square test. We performed logistic regression analysis to determine associations of RR among TB/HIV-coinfected patients. Results. Of the 303 patients, 182 (60.1%) were male, 111 (36.6%) had TB/HIV coinfection, and the median (interquartile range) age was 31 (25-39) years. RR was found among 58 (19.1%) patients. The prevalence of RR was 32.4% (36/111) (95% confidence interval (CI): 24-42) among TB/HIV-coinfected patients compared to 11.5% (22/192) (95% CI: 7–17) among HIV-negative TB patients ( ). Among TB/HIV-coinfected patients, those with RR were more likely to be rural residents (adjusted odds ratio (aOR): 5.24, 95% CI: 1.51–18.21, ) and have a very low bacillary load (aOR: 13.52, 95% CI: 3.15–58.08, ). Conclusion. There was a high prevalence of RR among TB/HIV-coinfected patients. RR was associated with rural residence and having a very low bacillary load among TB/HIV-coinfected patients. The findings highlight a need for universal access to drug susceptibility testing among TB/HIV-coinfected patients, especially in rural settings. |
Costa, Cecilia; Scabini, Silvia; Kaimal, Arvind; Kasozi, William; Cusato, Jessica; Kafufu, Bosco; Borderi, Marco; Mwaka, Erisa; Perri, Giovanni Di; Lamorde, Mohammed; Calcagno, Andrea; Castelnuovo, Barbara The Journal of Infectious Diseases, 222 (2), pp. 263-272, 2020. @article{Costa2020, title = {Calcaneal Quantitative Ultrasonography and Urinary Retinol-Binding Protein in Antiretroviral-Treated Patients With Human Immunodeficiency Virus in Uganda: A Pilot Study }, author = {Cecilia Costa and Silvia Scabini and Arvind Kaimal and William Kasozi and Jessica Cusato and Bosco Kafufu and Marco Borderi and Erisa Mwaka and Giovanni Di Perri and Mohammed Lamorde and Andrea Calcagno and Barbara Castelnuovo}, url = {https://academic.oup.com/jid/article-abstract/222/2/263/5766432}, doi = {https://doi.org/10.1093/infdis/jiaa088}, year = {2020}, date = {2020-07-15}, journal = {The Journal of Infectious Diseases}, volume = {222}, number = {2}, pages = {263-272}, abstract = {Abstract Background Data on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infected individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein–urinary creatinine ratio (uRBP/uCr) and reduced BMD. Methods We conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infected adults who had been receiving continuous antiretroviral therapy for ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection. Results DXA BMD measurements were significantly associated (P < .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [P = .03], femoral neck [P < .001], and total hip [P = .002]). Conclusions Calcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate–sparing regimens in resource-limited settings. bone metabolic diseases, HIV, calcaneal ultrasound, tubular impairment, resource-limited setting Topic: hiv ultrasonography bone mineral density calcaneus retinol binding proteins uganda urinary tract x-ray absorptiometry, dual-energy anti-retroviral agents }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Data on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infected individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein–urinary creatinine ratio (uRBP/uCr) and reduced BMD. Methods We conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infected adults who had been receiving continuous antiretroviral therapy for ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection. Results DXA BMD measurements were significantly associated (P < .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [P = .03], femoral neck [P < .001], and total hip [P = .002]). Conclusions Calcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate–sparing regimens in resource-limited settings. bone metabolic diseases, HIV, calcaneal ultrasound, tubular impairment, resource-limited setting Topic: hiv ultrasonography bone mineral density calcaneus retinol binding proteins uganda urinary tract x-ray absorptiometry, dual-energy anti-retroviral agents |
Alufandika, Melanie; Lawrence, David S; Boyer-Chammard, Timothée; Kanyama, Cecilia; Ndhlovu, Chiratidzo E; Mosepele, Mosepele; Tugume, Lillian; Meya, David; Boulware, David R; Rhein, Joshua; Muzoora, Conrad; Youssouf, Nabila; Molloy, Síle F; Schutz, Charlotte; Lortholary, Olivier; Meintjes, Graeme; Mwandumba, Henry C; Harrison, Thomas S; Jarvis, Joseph N; the Group, AMBITION-cm Study AIDS (London, England), 34 (9), pp. 1425–1428, 2020. @article{Alufandika2020, title = {A pragmatic approach to managing antiretroviral therapy-experienced patients diagnosed with HIV-associated cryptococcal meningitis: impact of antiretroviral therapy adherence and duration}, author = {Melanie Alufandika and David S. Lawrence and Timothée Boyer-Chammard and Cecilia Kanyama and Chiratidzo E. Ndhlovu and Mosepele Mosepele and Lillian Tugume and David Meya and David R. Boulware and Joshua Rhein and Conrad Muzoora and Nabila Youssouf and Síle F. Molloy and Charlotte Schutz and Olivier Lortholary and Graeme Meintjes and Henry C. Mwandumba and Thomas S. Harrison and Joseph N. Jarvis and the AMBITION-cm Study Group}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473821/}, doi = { doi: 10.1097/QAD.0000000000002556}, year = {2020}, date = {2020-07-15}, journal = {AIDS (London, England)}, volume = {34}, number = {9}, pages = {1425–1428}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Masyuko, Sarah J; Page, Stephanie T; and Kinuthia, John; Osoti, Alfred O; Polyak, Stephen J; Otieno, Fredrick C; Kibachio, Joseph M; Mogaka, Jerusha N; Temu, Tecla M; Zifodya, Jerry S; Otedo, Amos; Nakanjako, Damalie; Hughes, James P; Farquhar, Carey Metabolic syndrome and 10-year cardiovascular risk among HIV-positive and HIV-negative adults Journal Article Medicine (Baltimore)., 99 (27), pp. e20845, 2020. @article{Masyuko2020, title = {Metabolic syndrome and 10-year cardiovascular risk among HIV-positive and HIV-negative adults}, author = {Sarah J. Masyuko and Stephanie T. Page and and John Kinuthia and Alfred O. Osoti and Stephen J. Polyak and Fredrick C. Otieno and Joseph M. Kibachio and Jerusha N. Mogaka and Tecla M. Temu and Jerry S. Zifodya and Amos Otedo and Damalie Nakanjako and James P. Hughes and Carey Farquhar}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337552/}, doi = {doi: 10.1097/MD.0000000000020845}, year = {2020}, date = {2020-07-02}, journal = {Medicine (Baltimore).}, volume = {99}, number = {27}, pages = {e20845}, abstract = {Abstract To determine the prevalence and correlates of metabolic syndrome (MetS) and compare 10-year cardiovascular disease (CVD) risk among Kenyan adults with and without HIV infection. We conducted a cross-sectional study among adults ≥30 years of age with and without HIV infection seeking care at Kisumu County Hospital. Participants completed a health questionnaire and vital signs, anthropomorphic measurements, and fasting blood were obtained. MetS was defined using 2009 Consensus Criteria and 10-year Atherosclerotic CVD (ASCVD) risk score was calculated. Chi-square, independent t tests, Wilcoxon ranksum test and multivariable logistic regression were used to determine differences and associations between HIV and MetS, CVD risk factors and ASCVD risk score. A total of 300 people living with HIV (PLWHIV) and 298 HIV-negative participants with median age 44 years enrolled, 50% of whom were female. The prevalence of MetS was 8.9% overall, but lower among PLWHIV than HIV-negative participants (6.3% vs 11.6%, respectively; P = .001). The most prevalent MetS components were elevated blood pressure, decreased high density lipoprotein, and abdominal obesity. Adjusting for covariates, PLWHIV were 66% less likely to have MetS compared to HIV-negative participants (adjusted odds ratio [aOR] 0.34; 95% confidence interval [95%CI] 0.18, 0.65; P = .005). Median ASCVD risk score was also lower among PLWHIV compared to HIV-negative participants (1.7% vs 3.0%, P = .002). MetS was more common among HIV-negative than HIV-positive adults, and HIV-negative adults were at greater risk for CVD compared to PLWHIV. These data support integration of routine CVD screening and management into health programs in resource-limited settings, regardless of HIV status. Keywords: cardiovascular risk score, HIV, Kenya, metabolic syndrome}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract To determine the prevalence and correlates of metabolic syndrome (MetS) and compare 10-year cardiovascular disease (CVD) risk among Kenyan adults with and without HIV infection. We conducted a cross-sectional study among adults ≥30 years of age with and without HIV infection seeking care at Kisumu County Hospital. Participants completed a health questionnaire and vital signs, anthropomorphic measurements, and fasting blood were obtained. MetS was defined using 2009 Consensus Criteria and 10-year Atherosclerotic CVD (ASCVD) risk score was calculated. Chi-square, independent t tests, Wilcoxon ranksum test and multivariable logistic regression were used to determine differences and associations between HIV and MetS, CVD risk factors and ASCVD risk score. A total of 300 people living with HIV (PLWHIV) and 298 HIV-negative participants with median age 44 years enrolled, 50% of whom were female. The prevalence of MetS was 8.9% overall, but lower among PLWHIV than HIV-negative participants (6.3% vs 11.6%, respectively; P = .001). The most prevalent MetS components were elevated blood pressure, decreased high density lipoprotein, and abdominal obesity. Adjusting for covariates, PLWHIV were 66% less likely to have MetS compared to HIV-negative participants (adjusted odds ratio [aOR] 0.34; 95% confidence interval [95%CI] 0.18, 0.65; P = .005). Median ASCVD risk score was also lower among PLWHIV compared to HIV-negative participants (1.7% vs 3.0%, P = .002). MetS was more common among HIV-negative than HIV-positive adults, and HIV-negative adults were at greater risk for CVD compared to PLWHIV. These data support integration of routine CVD screening and management into health programs in resource-limited settings, regardless of HIV status. Keywords: cardiovascular risk score, HIV, Kenya, metabolic syndrome |
Lamorde, Mohammed; Atwiine, Martha; Owarwo, Noela C; Ddungu, Ahmed; Laker, Eva O; Mubiru, Frank; Kiragga, Agnes; Lwanga, Isaac B; Castelnuovo, Barbara Dolutegravir-associated hyperglycaemia in patients with HIV Journal Article The Lancet HIV, 7 (7), pp. e461-e462, 2020. @article{Lamorde2020, title = {Dolutegravir-associated hyperglycaemia in patients with HIV}, author = {Mohammed Lamorde and Martha Atwiine and Noela C Owarwo and Ahmed Ddungu and Eva O Laker and Frank Mubiru and Agnes Kiragga and Isaac B Lwanga and Barbara Castelnuovo}, url = {https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30042-4/fulltext}, doi = {https://doi.org/10.1016/S2352-3018(20)30042-4}, year = {2020}, date = {2020-07-01}, journal = {The Lancet HIV}, volume = {7}, number = {7}, pages = {e461-e462}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
andHailemichael Desalegn, Neil Gupta; Ocama, Ponsiano; Lacombe, Karine; Njouom, Richard; Afihene, Mary; Cunha, Lina; Spearman, Wendy C; Sonderup, Mark W; Kateera, Fredrick Converging pandemics: implications of COVID-19 for the viral hepatitis response in sub-Saharan Africa Journal Article The Lancet, Gastroenterology & Hepatology, 5 (7), pp. 634-636, 2020. @article{andHailemichaelDesalegn2020, title = {Converging pandemics: implications of COVID-19 for the viral hepatitis response in sub-Saharan Africa}, author = {Neil Gupta andHailemichael Desalegn and Ponsiano Ocama and Karine Lacombe and Richard Njouom and Mary Afihene and Lina Cunha and C Wendy Spearman and Mark W Sonderup and Fredrick Kateera}, url = {https://www.thelancet.com/journals/langas/article/PIIS2468-1253%2820%2930155-2/fulltext}, doi = {https://doi.org/10.1016/S2468-1253(20)30155-2}, year = {2020}, date = {2020-07-01}, journal = {The Lancet, Gastroenterology & Hepatology}, volume = {5}, number = {7}, pages = {634-636}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Wanga, Valentine; Baeten, Jared M; Bukusi, Elizabeth A; Mugo, Nelly R; Asiimwe, Stephen; Ngure, Kenneth; Mujugira, Andrew; Muwonge, Timothy; Odoyo, Josephine B; Haberer, Jessica E; Celum, Connie; on behalf of the Team, Renee Heffron Partners Demonstration Project Sexual Behavior and Perceived HIV Risk Among HIV-Negative Members of Serodiscordant Couples in East Africa Journal Article AIDS and Behavior, 24 (7), pp. pages2082–2090, 2020. @article{Wanga2020b, title = {Sexual Behavior and Perceived HIV Risk Among HIV-Negative Members of Serodiscordant Couples in East Africa}, author = {Valentine Wanga and Jared M. Baeten and Elizabeth A. Bukusi and Nelly R. Mugo and Stephen Asiimwe and Kenneth Ngure and Andrew Mujugira and Timothy Muwonge and Josephine B. Odoyo and Jessica E. Haberer and Connie Celum and Renee Heffron on behalf of the Partners Demonstration Project Team}, url = {https://link.springer.com/article/10.1007%2Fs10461-019-02773-5}, doi = {https://doi.org/10.1007/s10461-019-02773-5}, year = {2020}, date = {2020-07-01}, journal = {AIDS and Behavior}, volume = {24}, number = {7}, pages = { pages2082–2090}, abstract = {Abstract HIV risk perception may influence the use of HIV prevention interventions. Using data from HIV-negative adults enrolled in a study of pre-exposure prophylaxis (PrEP) and antiretroviral therapy for HIV-serodiscordant couples in Kenya and Uganda, we examined associations between: (1) condom use and risk perception and (2) risk perception and PrEP adherence. Two-thirds of HIV-negative partners reported condomless sex with their HIV-positive partner or another partner in the month prior to study enrollment. Compared to those who reported no condomless sex, participants who reported condomless sex during the month prior to study visit had fivefold higher odds of reporting “high risk” vs “no risk” perception (36.3 versus 10.9%: aOR 4.9, 95% CI 3.4–6.9). Reporting condomless sex in the most recent sex act was associated with increased odds of perceiving some HIV risk (aOR for high risk = 7.3, 95% CI 4.9–10.8; aOR for moderate risk = 4.8, 95% CI 3.5–6.7; aOR for low risk = 3.5, 95% CI 2.7–4.6). We found no significant association between risk perception and PrEP adherence. Sexual behavior aligned with perceived HIV risk, which can facilitate an HIV-negative individual’s decisions about PrEP use.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract HIV risk perception may influence the use of HIV prevention interventions. Using data from HIV-negative adults enrolled in a study of pre-exposure prophylaxis (PrEP) and antiretroviral therapy for HIV-serodiscordant couples in Kenya and Uganda, we examined associations between: (1) condom use and risk perception and (2) risk perception and PrEP adherence. Two-thirds of HIV-negative partners reported condomless sex with their HIV-positive partner or another partner in the month prior to study enrollment. Compared to those who reported no condomless sex, participants who reported condomless sex during the month prior to study visit had fivefold higher odds of reporting “high risk” vs “no risk” perception (36.3 versus 10.9%: aOR 4.9, 95% CI 3.4–6.9). Reporting condomless sex in the most recent sex act was associated with increased odds of perceiving some HIV risk (aOR for high risk = 7.3, 95% CI 4.9–10.8; aOR for moderate risk = 4.8, 95% CI 3.5–6.7; aOR for low risk = 3.5, 95% CI 2.7–4.6). We found no significant association between risk perception and PrEP adherence. Sexual behavior aligned with perceived HIV risk, which can facilitate an HIV-negative individual’s decisions about PrEP use. |
Avataneo, Valeria; de Nicolò, Amedeo; Cusato, Jessica; Antonucci, Miriam; Manca, Alessandra; Palermiti, Alice; Waitt, Catriona; Walimbwa, Stephen; Lamorde, Mohammed; di Perri, Giovanni; D’Avolio, Antonio Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease Journal Article Journal of Antimicrobial Chemotherapy, 75 (7), pp. 1772–1777, 2020. @article{Avataneo2020, title = {Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease }, author = {Valeria Avataneo and Amedeo de Nicolò and Jessica Cusato and Miriam Antonucci and Alessandra Manca and Alice Palermiti and Catriona Waitt and Stephen Walimbwa and Mohammed Lamorde and Giovanni di Perri and Antonio D’Avolio}, year = {2020}, date = {2020-07-01}, journal = {Journal of Antimicrobial Chemotherapy}, volume = {75}, number = {7}, pages = {1772–1777}, abstract = {Abstract Background Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. Objectives The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. Methods Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 μm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. Results Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. Conclusions This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak. Topic: ebola virus disease plasma prodrugs quality control united states food and drug administration guidelines pharmacokinetics metabolites remdesivir sars-cov-2 covid-19 }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. Objectives The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. Methods Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 μm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. Results Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. Conclusions This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak. Topic: ebola virus disease plasma prodrugs quality control united states food and drug administration guidelines pharmacokinetics metabolites remdesivir sars-cov-2 covid-19 |
Ssebambulidde, Kenneth; Segawa, Ivan; Laker, Eva; Lamorde, Mohammed; Castelnuovo, Barbara; Nakasujja, Noeline; Calcagno, Andrea Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda Journal Article Oxford Medical Case Reports, (6), pp. omz121, 2020, ( This is a correction to: Oxford Medical Case Reports, Volume 2019, Issue 2, February 2019, omy132, https://doi.org/10.1093/omcr/omy132 ). @article{Ssebambulidde2020, title = {Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda }, author = { Kenneth Ssebambulidde and Ivan Segawa and Eva Laker and Mohammed Lamorde and Barbara Castelnuovo and Noeline Nakasujja and Andrea Calcagno}, url = {https://academic.oup.com/omcr/article/2020/6/omz121/5862477}, doi = {doi.org/10.1093/omcr/omz121}, year = {2020}, date = {2020-06-25}, journal = {Oxford Medical Case Reports}, number = {6}, pages = {omz121}, abstract = {Abstract Two HIV-infected individuals on second-line atazanavir-based antiretroviral therapy presented with neuropsychiatric symptoms. Cerebrospinal fluid HIV RNA was higher than plasma HIV RNA and antiretroviral regimens’ optimization led to prompt resolution of symptoms in one. Patients on second-line atazanavir-based antiretroviral therapy with documented previous treatment failure may be at risk of symptomatic cerebrospinal fluid escape.}, note = { This is a correction to: Oxford Medical Case Reports, Volume 2019, Issue 2, February 2019, omy132, https://doi.org/10.1093/omcr/omy132 }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Two HIV-infected individuals on second-line atazanavir-based antiretroviral therapy presented with neuropsychiatric symptoms. Cerebrospinal fluid HIV RNA was higher than plasma HIV RNA and antiretroviral regimens’ optimization led to prompt resolution of symptoms in one. Patients on second-line atazanavir-based antiretroviral therapy with documented previous treatment failure may be at risk of symptomatic cerebrospinal fluid escape. |
Kwizera, Richard; Wadda, Vincent; Mugenyi, Levicatus; Aanyu-tukamuhebwa, Hellen; Yimer, George Nyale Getnet; Chakaya, Jeremiah; jong, Corina De; der molen, Thys Van; Denning, David W; Gore, Robin; Kirenga, Bruce J Skin prick reactivity among asthmatics in East Africa Journal Article World Allergy Organization Journal, 13 (6), pp. 100130, 2020. @article{Kwizera2020c, title = {Skin prick reactivity among asthmatics in East Africa}, author = {Richard Kwizera and Vincent Wadda and Levicatus Mugenyi and Hellen Aanyu-tukamuhebwa and George Nyale Getnet Yimer and Jeremiah Chakaya and Corina De jong and Thys Van der molen and David W. Denning and Robin Gore and Bruce J. Kirenga }, url = {https://www.sciencedirect.com/science/article/pii/S1939455120300338}, doi = {https://doi.org/10.1016/j.waojou.2020.100130}, year = {2020}, date = {2020-06-23}, journal = {World Allergy Organization Journal}, volume = {13}, number = {6}, pages = {100130}, abstract = {Abstract Background The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. Methods From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. Results Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. Conclusion There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. Trial registration The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. Methods From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. Results Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. Conclusion There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. Trial registration The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017. |
Bell, David; Hansen, Kristian Schultz; Kiragga, Agnes N; Kambugu, Andrew; Kissa, John; and Mbonye, Anthony K Predicting the Impact of COVID-19 and the Potential Impact of the Public Health Response on Disease Burden in Uganda Journal Article The American Journal of Tropical Medicine and Hygiene, 103 (3), pp. 1191–1197 , 2020. @article{Bell2020, title = {Predicting the Impact of COVID-19 and the Potential Impact of the Public Health Response on Disease Burden in Uganda}, author = {David Bell and Kristian Schultz Hansen and Agnes N. Kiragga and Andrew Kambugu and John Kissa and and Anthony K. Mbonye}, url = {https://www.ajtmh.org/search?f_0=author&q_0=John+Kissa}, doi = {https://doi.org/10.4269/ajtmh.20-0546}, year = {2020}, date = {2020-06-23}, journal = {The American Journal of Tropical Medicine and Hygiene}, volume = {103}, number = {3}, pages = {1191–1197 }, abstract = {The COVID-19 pandemic and public health “lockdown” responses in sub-Saharan Africa, including Uganda, are now widely reported. Although the impact of COVID-19 on African populations has been relatively light, it is feared that redirecting focus and prioritization of health systems to fight COVID-19 may have an impact on access to non–COVID-19 diseases. We applied age-based COVID-19 mortality data from China to the population structures of Uganda and non-African countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. We then predicted the impact of possible scenarios of the COVID-19 public health response on morbidity and mortality for HIV/AIDS, malaria, and maternal health in Uganda. Based on population age structure alone, Uganda is predicted to have a relatively low COVID-19 burden compared with an equivalent transmission in comparison countries, with 12% of the mortality and 19% of the lost DALYs predicted for an equivalent transmission in Italy. By contrast, scenarios of the impact of the public health response on malaria and HIV/AIDS predict additional disease burdens outweighing that predicted from extensive SARS-CoV-2 transmission. Emerging disease data from Uganda suggest that such deterioration may already be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non–COVID-19 disease burden from a prolonged lockdown response. This may reverse hard-won gains in addressing fundamental vulnerabilities in women and children’s health, and underlines the importance of tailoring COVID-19 responses according to population structure and local disease vulnerabilities.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The COVID-19 pandemic and public health “lockdown” responses in sub-Saharan Africa, including Uganda, are now widely reported. Although the impact of COVID-19 on African populations has been relatively light, it is feared that redirecting focus and prioritization of health systems to fight COVID-19 may have an impact on access to non–COVID-19 diseases. We applied age-based COVID-19 mortality data from China to the population structures of Uganda and non-African countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. We then predicted the impact of possible scenarios of the COVID-19 public health response on morbidity and mortality for HIV/AIDS, malaria, and maternal health in Uganda. Based on population age structure alone, Uganda is predicted to have a relatively low COVID-19 burden compared with an equivalent transmission in comparison countries, with 12% of the mortality and 19% of the lost DALYs predicted for an equivalent transmission in Italy. By contrast, scenarios of the impact of the public health response on malaria and HIV/AIDS predict additional disease burdens outweighing that predicted from extensive SARS-CoV-2 transmission. Emerging disease data from Uganda suggest that such deterioration may already be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non–COVID-19 disease burden from a prolonged lockdown response. This may reverse hard-won gains in addressing fundamental vulnerabilities in women and children’s health, and underlines the importance of tailoring COVID-19 responses according to population structure and local disease vulnerabilities. |
Bochner, Aaron F; Baeten, Jared M; Secor, Evan W; van Dam, Govert J; Szpiro, Adam A; Njenga, Sammy M; Corstjens, Paul L A M; Newsam, Austin; Mugo, Nelly R; Celum, Connie; Mujugira, Andrew; McClelland, Scott R; Barnabas, Ruanne V Associations between schistosomiasis and HIV‐1 acquisition risk in four prospective cohorts: a nested case‐control analysis Journal Article Journal of the International AIDS Society, 23 (6), pp. e25534, 2020. @article{Bochner2020, title = {Associations between schistosomiasis and HIV‐1 acquisition risk in four prospective cohorts: a nested case‐control analysis}, author = {Aaron F Bochner and Jared M Baeten and W Evan Secor and Govert J van Dam and Adam A Szpiro and Sammy M Njenga and Paul L A M Corstjens and Austin Newsam and Nelly R Mugo and Connie Celum and Andrew Mujugira and R Scott McClelland and Ruanne V Barnabas }, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25534}, doi = {https://doi.org/10.1002/jia2.25534}, year = {2020}, date = {2020-06-23}, journal = {Journal of the International AIDS Society}, volume = {23}, number = {6}, pages = {e25534}, abstract = { Abstract Introduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub‐Saharan Africa. Schistosomiasis is hypothesized to increase HIV‐1 acquisition risk, and multiple cross‐sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods We conducted nested case‐control analyses within three longitudinal cohorts of heterosexual HIV‐1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow‐up from 1993 to 2014. Cases HIV‐1 seroconverted during prospective follow‐up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV‐1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results We included 245 HIV‐1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV‐1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV‐1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species‐specific effects, there was no statistically significant association between HIV‐1 acquisition risk and Schistosoma mansoni (serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) or Schistosoma haematobium (serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions Schistosomiasis was not a strong risk factor for HIV‐1 acquisition in these four prospective studies. S. mansoni was responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis that S. mansoni infection is associated with increased HIV‐1 acquisition risk. S. haematobium infection was associated with a point estimate of elevated HIV‐1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Introduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub‐Saharan Africa. Schistosomiasis is hypothesized to increase HIV‐1 acquisition risk, and multiple cross‐sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods We conducted nested case‐control analyses within three longitudinal cohorts of heterosexual HIV‐1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow‐up from 1993 to 2014. Cases HIV‐1 seroconverted during prospective follow‐up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV‐1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results We included 245 HIV‐1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV‐1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV‐1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species‐specific effects, there was no statistically significant association between HIV‐1 acquisition risk and Schistosoma mansoni (serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) or Schistosoma haematobium (serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions Schistosomiasis was not a strong risk factor for HIV‐1 acquisition in these four prospective studies. S. mansoni was responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis that S. mansoni infection is associated with increased HIV‐1 acquisition risk. S. haematobium infection was associated with a point estimate of elevated HIV‐1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts. |
Mujugira, Andrew; Hendrix, Craig; Glidden, David V; Donnell, Deborah; GuohongWang, ; Baeten, Jared M; Marzinke, Mark; Spinelli, Matthew A; Vincent, Michael; Gandhi, Monica; Mugo, Nelly; Team, Partners PrEP Study; Stalter, Randy M; Rodrigues, Warren C Urine Tenofovir Levels Measured by a Novel Immunoassay Predict HIV Protection Journal Article National AIDS Treatment Advocacy Project, 2020. @article{Mujugira2020, title = {Urine Tenofovir Levels Measured by a Novel Immunoassay Predict HIV Protection}, author = {Andrew Mujugira and Craig Hendrix and David V Glidden and Deborah Donnell and GuohongWang and Jared M Baeten and Mark Marzinke and Matthew A Spinelli and Michael Vincent and Monica Gandhi and Nelly Mugo and Partners PrEP Study Team and Randy M Stalter and Warren C Rodrigues}, url = {https://www.natap.org/2020/HIV/ciaa785.pdf}, doi = {doi:10.1093/cid/ciaa785}, year = {2020}, date = {2020-06-23}, journal = {National AIDS Treatment Advocacy Project}, abstract = {Abstract New tools are needed to support PrEPadherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir. Keywords: PrEP, HIV prevention, urine, immunoassay, ELISA}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract New tools are needed to support PrEPadherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir. Keywords: PrEP, HIV prevention, urine, immunoassay, ELISA |
