Peer Reviewed Publications
2020 |
L, Nakiire; H, Mwanja; SK, Pillai; J, Gasanani; D, Ntungire; S, Nsabiyumva; MID, Mafigiri R;; N, Muneza; SE, Ward; Z, Daffe; PB, Ahabwe; MBAIT, Kyazze S;; J, Ojwang; J, Homsy; E, Mclntyre; M, Lamorde; R, Walwema; I, Makumbi; amd RD., Muruta Merrill A Morbidity and Mortality Weekly Report - CDC 2020, visited: 10.01.2020. @online{L2020, title = {Population Movement Patterns Among the Democratic Republic of the Congo, Rwanda, and Uganda During an Outbreak of Ebola Virus Disease: Results from Community Engagement in Two Districts — Uganda, March 2019}, author = {Nakiire L and Mwanja H and Pillai SK and Gasanani J and Ntungire D and Nsabiyumva S and Mafigiri R; MID and Muneza N and Ward SE and Daffe Z and Ahabwe PB and Kyazze S; MBAIT and Ojwang J and Homsy J and Mclntyre E and Lamorde M and Walwema R and Makumbi I and Muruta A amd Merrill RD. }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973344/ }, doi = {doi: 10.15585/mmwr.mm6901a3 }, year = {2020}, date = {2020-01-10}, urldate = {2020-01-10}, organization = {Morbidity and Mortality Weekly Report - CDC}, keywords = {}, pubstate = {published}, tppubtype = {online} } |
2019 |
YC, Manabe; H, Nambooze; ES, Okello; MR, Kamya; ET, Katabira; I, Ssinabulya; M, Kaddumukasa; Y, Nabunnya; RC, Bollinger; NK., Sewankambo Group Mentorship Model to Enhance the Efficiency and Productivity of PhD Research Training in Sub-Saharan Africa. Journal Article Annals of Global Health, 84 (1), pp. 170-175, 2019. @article{YC2019, title = {Group Mentorship Model to Enhance the Efficiency and Productivity of PhD Research Training in Sub-Saharan Africa. }, author = {Manabe YC and Nambooze H and Okello ES and Kamya MR and Katabira ET and Ssinabulya I and Kaddumukasa M and Nabunnya Y and Bollinger RC and Sewankambo NK. }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748251/ }, doi = {10.29024/aogh.25}, year = {2019}, date = {2019-09-19}, journal = {Annals of Global Health}, volume = {84}, number = {1}, pages = {170-175}, abstract = {INTRODUCTION: High quality PhD training in sub-Saharan Africa is important to strengthen research evidence to advance development and health. Training a critical mass of independent investigators capable of original scientific research requires strong mentorship, research environments, and international networks. We sought to iteratively improve a PhD training model in Uganda through systems capacity building. METHODS: PhD students were selected through a rigorous competitive application and selection process, which included a written proposal and a face-to-face panel interview. The program provided administrative support, paid tuition fees, tools (space, equipment, research money), skills (short research courses on study design, biostatistics, manuscript and grant writing), and infrastructure (finance, grants management support, and lab infrastructure). Guidance to identify local and international mentorship was also provided in addition to two to three group meetings per year where data was presented and progress assessed by the program leaders in addition to available local mentors. RESULTS: Seventeen PhD students were selected, and fifteen will complete training through the MEPI-MESAU program. To date, 60% have completed, including 2 students who started 2 years into the program. So far, 169 publications have been published in the peer-reviewed literature. Our PhD students have supervised and mentored 65 Master's students, which illustrates the cascade effect of PhD training on the academic medical school environment. CONCLUSIONS: The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: High quality PhD training in sub-Saharan Africa is important to strengthen research evidence to advance development and health. Training a critical mass of independent investigators capable of original scientific research requires strong mentorship, research environments, and international networks. We sought to iteratively improve a PhD training model in Uganda through systems capacity building. METHODS: PhD students were selected through a rigorous competitive application and selection process, which included a written proposal and a face-to-face panel interview. The program provided administrative support, paid tuition fees, tools (space, equipment, research money), skills (short research courses on study design, biostatistics, manuscript and grant writing), and infrastructure (finance, grants management support, and lab infrastructure). Guidance to identify local and international mentorship was also provided in addition to two to three group meetings per year where data was presented and progress assessed by the program leaders in addition to available local mentors. RESULTS: Seventeen PhD students were selected, and fifteen will complete training through the MEPI-MESAU program. To date, 60% have completed, including 2 students who started 2 years into the program. So far, 169 publications have been published in the peer-reviewed literature. Our PhD students have supervised and mentored 65 Master's students, which illustrates the cascade effect of PhD training on the academic medical school environment. CONCLUSIONS: The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others. |
Ahimbisibwe, Cynthia; Kwizera, Richard; Ndyetukira, Jane Frances; Kugonza, Florence; Sadiq, Alisat; Hullsiek, Kathy Huppler; Williams, Darlisha A; Rhein, Joshua; Boulware, David R; Meya, David B BMC Infectious Diseases , 19 (1), pp. 558, 2019. @article{Ahimbisibwe2019, title = {Management of amphotericin-induced phlebitis among HIV patients with cryptococcal meningitis in a resource-limited setting: a prospective cohort study. }, author = {Cynthia Ahimbisibwe and Richard Kwizera and Jane Frances Ndyetukira and Florence Kugonza and Alisat Sadiq and Kathy Huppler Hullsiek and Darlisha A. Williams and Joshua Rhein and David R. Boulware and David B. Meya}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595678/}, doi = {doi: 10.1186/s12879-019-4209-7}, year = {2019}, date = {2019-09-19}, journal = {BMC Infectious Diseases }, volume = {19}, number = {1}, pages = {558}, abstract = {BACKGROUND: Amphotericin-induced phlebitis is a common infusion-related reaction in patients managed for cryptococcal meningitis. High-quality nursing care is critical component to successful cryptococcosis treatment. We highlight the magnitude and main approaches in the management of amphotericin-induced phlebitis and the challenges faced in resource-limited settings. METHODS: We prospectively determined the incidence of amphotericin-induced phlebitis during clinical trials in Kampala, Uganda from 2013 to 2018. We relate practical strategies and challenges faced in clinical management of phlebitis. RESULTS: Overall, 696 participants were diagnosed with HIV-related cryptococcal meningitis. Participants received 7-14 doses of intravenous (IV) amphotericin B deoxycholate 0.7-1.0 mg/kg/day for induction therapy through peripheral IV lines at a concentration of 0.1 mg/mL in 5% dextrose. Overall, 18% (125/696) developed amphotericin-induced phlebitis. We used four strategies to minimize/prevent the occurrence of phlebitis. First, after every dose of amphotericin, we gave one liter of intravenous normal saline. Second, we rotated IV catheters every three days. Third, we infused IV amphotericin over 4 h. Finally, early ambulation was encouraged to minimize phlebitis. To alleviate phlebitis symptoms, warm compresses were used. In severe cases, treatment included topical diclofenac gel and oral anti-inflammatory medicines. Antibiotics were used only when definite signs of infection developed. Patient/caregivers' education was vital in implementing these management strategies. Major challenges included implementing these interventions in participants with altered mental status and limited access to topical and oral anti-inflammatory medicines in resource-limited settings. CONCLUSIONS: Amphotericin-induced phlebitis is common with amphotericin, yet phlebitis is a preventable complication even in resource-limited settings. TRIAL REGISTRATION: The ASTRO-CM trial was registered prospectively. ClincalTrials.gov : NCT01802385 ; Registration date: March 1, 2013; Last verified: February 14, 2018.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Amphotericin-induced phlebitis is a common infusion-related reaction in patients managed for cryptococcal meningitis. High-quality nursing care is critical component to successful cryptococcosis treatment. We highlight the magnitude and main approaches in the management of amphotericin-induced phlebitis and the challenges faced in resource-limited settings. METHODS: We prospectively determined the incidence of amphotericin-induced phlebitis during clinical trials in Kampala, Uganda from 2013 to 2018. We relate practical strategies and challenges faced in clinical management of phlebitis. RESULTS: Overall, 696 participants were diagnosed with HIV-related cryptococcal meningitis. Participants received 7-14 doses of intravenous (IV) amphotericin B deoxycholate 0.7-1.0 mg/kg/day for induction therapy through peripheral IV lines at a concentration of 0.1 mg/mL in 5% dextrose. Overall, 18% (125/696) developed amphotericin-induced phlebitis. We used four strategies to minimize/prevent the occurrence of phlebitis. First, after every dose of amphotericin, we gave one liter of intravenous normal saline. Second, we rotated IV catheters every three days. Third, we infused IV amphotericin over 4 h. Finally, early ambulation was encouraged to minimize phlebitis. To alleviate phlebitis symptoms, warm compresses were used. In severe cases, treatment included topical diclofenac gel and oral anti-inflammatory medicines. Antibiotics were used only when definite signs of infection developed. Patient/caregivers' education was vital in implementing these management strategies. Major challenges included implementing these interventions in participants with altered mental status and limited access to topical and oral anti-inflammatory medicines in resource-limited settings. CONCLUSIONS: Amphotericin-induced phlebitis is common with amphotericin, yet phlebitis is a preventable complication even in resource-limited settings. TRIAL REGISTRATION: The ASTRO-CM trial was registered prospectively. ClincalTrials.gov : NCT01802385 ; Registration date: March 1, 2013; Last verified: February 14, 2018. |
PL, Ponatshego; DS, Lawrence; N, Youssouf; SF, Molloy; M, Alufandika; F, Bango; DR, Boulware; C, Chawinga; E, Dziwani; E, Gondwe; A, Hlupeni; MC, Hosseinipour; C, Kanyama; DB, Meya; M, Mosepele; C, Muthoga; CK, Muzoora; H, Mwandumba; CE, Ndhlovu; R, Rajasingham; S, Sayed; S, Shamu; K, Tsholo; L, Tugume; D, Williams; H, Maheswaran; T, Shiri; T, Boyer-Chammard; A, Loyse; T, Chen; D, Wang; O, Lortholary; DG, Lalloo; G, Meintjes; S, Jaffar; TS, Harrison; JN, Jarvis; LW, Niessen BMJ Open, 9 (4), pp. 1-8, 2019. @article{PL2019, title = {AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study}, author = {Ponatshego PL and Lawrence DS and Youssouf N and Molloy SF and Alufandika M and Bango F and Boulware DR and Chawinga C and Dziwani E and Gondwe E and Hlupeni A and Hosseinipour MC and Kanyama C and Meya DB and Mosepele M and Muthoga C and Muzoora CK and Mwandumba H and Ndhlovu CE and Rajasingham R and Sayed S and Shamu S and Tsholo K and Tugume L and Williams D and Maheswaran H and Shiri T and Boyer-Chammard T and Loyse A and Chen T and Wang D and Lortholary O and Lalloo DG and Meintjes G and Jaffar S and Harrison TS and Jarvis JN and Niessen LW}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500286/pdf/bmjopen-2018-026288.pdf}, doi = {10.1136/bmjopen-2018-026288}, year = {2019}, date = {2019-08-27}, journal = {BMJ Open}, volume = {9}, number = {4}, pages = {1-8}, abstract = {INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results. |
L, Mukaremera; TR, McDonald; JN, Nielsen; CJ, Molenaar; A, Akampurira; C, Schutz; K, Taseera; C, Muzoora; G, Meintjes; DB, Meya; andNielsen K, Boulware DR Infection and Immunity , 87 (5), 2019. @article{L2019b, title = {The Mouse Inhalation Model of Cryptococcus neoformans Infection Recapitulates Strain Virulence in Humans and Shows that Closely Related Strains Can Possess Differential Virulence}, author = {Mukaremera L and McDonald TR and Nielsen JN and Molenaar CJ and Akampurira A and Schutz C and Taseera K and Muzoora C and Meintjes G and Meya DB and Boulware DR andNielsen K}, url = {https://iai.asm.org/content/87/5/e00046-19}, doi = {10.1128/IAI.00046-19}, year = {2019}, date = {2019-08-27}, journal = {Infection and Immunity }, volume = {87}, number = {5}, abstract = {Cryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet the Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with the clinical outcome, but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with Cryptococcus neoformans strains with the same multilocus sequence type (MLST). Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome was not associated with the patient CD4 count. Patient mortality was associated with higher cryptococcal antigen levels, the cerebrospinal fluid (CSF) fungal burden by quantitative culture, and low CSF fungal clearance. The virulence of a subset of clinical strains with the same sequence type was analyzed using a mouse inhalation model of cryptococcosis. We showed a strong association between human and mouse mortality rates, demonstrating that the mouse inhalation model recapitulates human infection. Similar to human infection, the ability to multiply in vivo, demonstrated by a high fungal burden in lung and brain tissues, was associated with mouse mortality. Mouse survival time was not associated with single C. neoformans virulence factors in vitro or in vivo; rather, a trend in survival time correlated with a suite of traits. These observations show that MLST-derived genotype similarities between C. neoformans strains do not necessarily translate into similar virulence either in the mouse model or in human patients. In addition, our results show that in vitro assays do not fully reproduce in vivo conditions that influence C. neoformans virulence. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Cryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet the Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with the clinical outcome, but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with Cryptococcus neoformans strains with the same multilocus sequence type (MLST). Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome was not associated with the patient CD4 count. Patient mortality was associated with higher cryptococcal antigen levels, the cerebrospinal fluid (CSF) fungal burden by quantitative culture, and low CSF fungal clearance. The virulence of a subset of clinical strains with the same sequence type was analyzed using a mouse inhalation model of cryptococcosis. We showed a strong association between human and mouse mortality rates, demonstrating that the mouse inhalation model recapitulates human infection. Similar to human infection, the ability to multiply in vivo, demonstrated by a high fungal burden in lung and brain tissues, was associated with mouse mortality. Mouse survival time was not associated with single C. neoformans virulence factors in vitro or in vivo; rather, a trend in survival time correlated with a suite of traits. These observations show that MLST-derived genotype similarities between C. neoformans strains do not necessarily translate into similar virulence either in the mouse model or in human patients. In addition, our results show that in vitro assays do not fully reproduce in vivo conditions that influence C. neoformans virulence. |
Bongomin, Felix; Kwizera, Richard; Atukunda, Angella; J.Kirenga, Bruce Cor pulmonale complicating chronic pulmonary aspergillosis with fatal consequences: Experience from Uganda. Journal Article Medical Mycology Case Reports, 25 (1), pp. 22-24, 2019. @article{Bongomin2019, title = {Cor pulmonale complicating chronic pulmonary aspergillosis with fatal consequences: Experience from Uganda.}, author = {Felix Bongomin and Richard Kwizera and Angella Atukunda and Bruce J.Kirenga}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614533/}, doi = { 10.1016/j.mmcr.2019.07.001}, year = {2019}, date = {2019-08-26}, journal = {Medical Mycology Case Reports}, volume = {25}, number = {1}, pages = {22-24}, abstract = {Cor pulmonale is a rare complication of pulmonary aspergillosis (CPA). A 45-year-old Ugandan male with a history of recurrent community-acquired pneumonias was admitted with symptoms of progressive difficulty in breathing, chronic productive cough, non-exertional left sided chest pain and progressive weight loss occurring over a 12-month period. Chest CT scan and echocardiography confirmed the diagnosis of CPA with an aspergilloma complicating bronchiectasis, complicated with cor pulmonale. However, this was previously clinically misdiagnosed as PTB.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cor pulmonale is a rare complication of pulmonary aspergillosis (CPA). A 45-year-old Ugandan male with a history of recurrent community-acquired pneumonias was admitted with symptoms of progressive difficulty in breathing, chronic productive cough, non-exertional left sided chest pain and progressive weight loss occurring over a 12-month period. Chest CT scan and echocardiography confirmed the diagnosis of CPA with an aspergilloma complicating bronchiectasis, complicated with cor pulmonale. However, this was previously clinically misdiagnosed as PTB. |
Nakalembe, Miriam; Philippa, Makanga; Frank, Mubiru; Megan, Swanson; Jeffrey, Martin; Megan, Huchko Infectious Agents and Cancer, 14 (14), pp. 1-10, 2019. @article{Nakalembe2019, title = {Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda.}, author = { Miriam Nakalembe and Makanga Philippa and Mubiru Frank and Swanson Megan and Martin Jeffrey and Huchko Megan}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515623/pdf/13027_2019_Article_230.pdf}, doi = {10.1186/s13027-019-0230-0}, year = {2019}, date = {2019-08-26}, journal = {Infectious Agents and Cancer}, volume = {14}, number = {14}, pages = {1-10}, abstract = {Background: New strategies are needed to combat the high incidence of cervical cancer in resource-limited settings such as sub-Saharan Africa. Screening for high-risk human papillomavirus (hrHPV) DNA is sensitive for pre-cancer, but its lack of specificity results in substantial overtreatment in low resource settings where additional testing (e.g., colposcopy) is rarely available. Testing for hrHPV E6/E7 mRNA may enhance specificity, but little is known about its performance characteristics in resource-limited settings. Methods: In a series of community health fairs in rural Uganda, women aged 25 to 49 years provided self-collected vaginal samples, which were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) E6/E7 mRNA with the Aptima® assay. Positive specimens underwent testing for HPV-16 and 18/45. After excluding pregnant women, all women testing positive for any hrHPV subsequently were offered cervical biopsy to determine pathology. Results: A total of 1892 women provided a vaginal sample for hrHPV testing during 24 health fairs. The median age was 34 years, HIV prevalence was 10, and 95% had not been previously screened. Prevalence of any hrHPV E6/E7 mRNA was 21% (95% confidence interval (CI): 19 to 23%); the prevalence of HPV-16 was 2.6%, HPV-18/45 1.9%, and HPV 16 and 18/45 were jointly found in 0.1% of the study population. Younger age, pregnancy and HIV-positivity were independently associated with any hrHPV infection. Of the 255 evaluable cervical biopsies, the positive predictive value of detecting any hrHPV E6/E7 mRNA for presence of cervical intraepithelial neoplasia grade 2 or higher ("CIN 2+") was 8.2% (95% CI: 5.1 to 12%). The positive predictive value associated with detection of HPV-16 mRNA (15%) or HPV-18/45 mRNA (15%) was only slightly higher. Conclusion: Among community-based women in Uganda, the prevalence of any hrHPV E6/E7 mRNA in vaginal samples was high, but the prevalence of the most oncogenic HPV types (16, 18, or 45) was substantially lower. Positive predictive value of hrHPV mRNA-positivity for CIN 2+ was also low, including when restricting to HPV 16/18/45-positivity. The findings emphasize the need to identify more specific screening approaches for cervical cancer.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: New strategies are needed to combat the high incidence of cervical cancer in resource-limited settings such as sub-Saharan Africa. Screening for high-risk human papillomavirus (hrHPV) DNA is sensitive for pre-cancer, but its lack of specificity results in substantial overtreatment in low resource settings where additional testing (e.g., colposcopy) is rarely available. Testing for hrHPV E6/E7 mRNA may enhance specificity, but little is known about its performance characteristics in resource-limited settings. Methods: In a series of community health fairs in rural Uganda, women aged 25 to 49 years provided self-collected vaginal samples, which were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) E6/E7 mRNA with the Aptima® assay. Positive specimens underwent testing for HPV-16 and 18/45. After excluding pregnant women, all women testing positive for any hrHPV subsequently were offered cervical biopsy to determine pathology. Results: A total of 1892 women provided a vaginal sample for hrHPV testing during 24 health fairs. The median age was 34 years, HIV prevalence was 10, and 95% had not been previously screened. Prevalence of any hrHPV E6/E7 mRNA was 21% (95% confidence interval (CI): 19 to 23%); the prevalence of HPV-16 was 2.6%, HPV-18/45 1.9%, and HPV 16 and 18/45 were jointly found in 0.1% of the study population. Younger age, pregnancy and HIV-positivity were independently associated with any hrHPV infection. Of the 255 evaluable cervical biopsies, the positive predictive value of detecting any hrHPV E6/E7 mRNA for presence of cervical intraepithelial neoplasia grade 2 or higher ("CIN 2+") was 8.2% (95% CI: 5.1 to 12%). The positive predictive value associated with detection of HPV-16 mRNA (15%) or HPV-18/45 mRNA (15%) was only slightly higher. Conclusion: Among community-based women in Uganda, the prevalence of any hrHPV E6/E7 mRNA in vaginal samples was high, but the prevalence of the most oncogenic HPV types (16, 18, or 45) was substantially lower. Positive predictive value of hrHPV mRNA-positivity for CIN 2+ was also low, including when restricting to HPV 16/18/45-positivity. The findings emphasize the need to identify more specific screening approaches for cervical cancer. |
FS, Sarfo; B, Castelnuovo; I, Fanti; T, Feldt; F, Incardona; R, Kaiser; I, Lwanga; G, Marrone; A, Sonnerborg; TB, Tufa; M, Zazzi; A., De Luca Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics Journal Article The Journal of Infection, 75 (5), pp. 402-408, 2019. @article{FS2019, title = {Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics}, author = {Sarfo FS and Castelnuovo B and Fanti I and Feldt T and Incardona F and Kaiser R and Lwanga I and Marrone G and Sonnerborg A and Tufa TB and Zazzi M and De Luca A.}, url = {https://www.idi-makerere.com/wp-content/uploads/2019/08/10.1016@j.jinf_.2019.03.003-3.pdf}, doi = {10.1016/j.jinf.2019.03.003}, year = {2019}, date = {2019-08-26}, journal = {The Journal of Infection}, volume = {75}, number = {5}, pages = {402-408}, abstract = {OBJECTIVES: Data on the longer-term effectiveness of second line combination antiretroviral therapy (ART) in sub-Saharan Africa (SSA) are lacking. We sought to assess the probability and determinants of 2nd line ART failure in SSA. METHODS: A retrospective, multi-center study of 2nd line ART initiated between 2005 and 2017 at four ART centers in Ethiopia, Ghana and Uganda. Main outcome measure was virologic failure (VF) defined as VL>1000 copies/ml after >6 months on 2nd line therapy. Predictors of VF and virologic re-suppression on 2nd line were evaluated using Cox Proportional Hazards and multivariable logistic regression models, respectively. RESULTS: 2191 subjects started 2nd line therapy, 61.5% females. Switching from 1st line (56.4% NVP-based, 70.3% including thymidine-analogues) to 2nd line therapy occurred after mean of 4.1 years. 98.9% of patients started boosted PI with NRTI backbone (TDF+3TC/FTC 67.3%, AZT+3TC 18.5%, others 14.2%). There were 267 (12.0%) VF with a 5-year estimated probability of 15.0% (95% CI 13.2-16.9). Key determinants of VF were concomitant rifampicin use (aHR 2.50 [95% CI 1.54-4.05]) and clinical/immunological failure versus virologic failure as reason for switching therapy (aHR, 0.53 [0.33-0.86]). 138 of 267 (51.7%) subsequently achieved virologic re-suppression and predictors included HIV RNA levels at 2nd-line failure: +1 log higher aOR 0.59 [0.43-0.80], experiencing change within 2nd line ART before VF: aOR 0.17 [0.05-0.56], and more recent calendar year of 2nd line initiation: aOR 0.85 [0.75-0.94].}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVES: Data on the longer-term effectiveness of second line combination antiretroviral therapy (ART) in sub-Saharan Africa (SSA) are lacking. We sought to assess the probability and determinants of 2nd line ART failure in SSA. METHODS: A retrospective, multi-center study of 2nd line ART initiated between 2005 and 2017 at four ART centers in Ethiopia, Ghana and Uganda. Main outcome measure was virologic failure (VF) defined as VL>1000 copies/ml after >6 months on 2nd line therapy. Predictors of VF and virologic re-suppression on 2nd line were evaluated using Cox Proportional Hazards and multivariable logistic regression models, respectively. RESULTS: 2191 subjects started 2nd line therapy, 61.5% females. Switching from 1st line (56.4% NVP-based, 70.3% including thymidine-analogues) to 2nd line therapy occurred after mean of 4.1 years. 98.9% of patients started boosted PI with NRTI backbone (TDF+3TC/FTC 67.3%, AZT+3TC 18.5%, others 14.2%). There were 267 (12.0%) VF with a 5-year estimated probability of 15.0% (95% CI 13.2-16.9). Key determinants of VF were concomitant rifampicin use (aHR 2.50 [95% CI 1.54-4.05]) and clinical/immunological failure versus virologic failure as reason for switching therapy (aHR, 0.53 [0.33-0.86]). 138 of 267 (51.7%) subsequently achieved virologic re-suppression and predictors included HIV RNA levels at 2nd-line failure: +1 log higher aOR 0.59 [0.43-0.80], experiencing change within 2nd line ART before VF: aOR 0.17 [0.05-0.56], and more recent calendar year of 2nd line initiation: aOR 0.85 [0.75-0.94]. |
I, Surowiec; T, Skotare; R, Sjögren; S, Gouveia-Figueira; J, Orikiiriza; S, Bergström; J, Normark; J, Trygg Joint and unique multiblock analysis of biological data - multiomics malaria study Journal Article Faraday Discussions, 218 , 2019. @article{I2019, title = {Joint and unique multiblock analysis of biological data - multiomics malaria study}, author = {Surowiec I and Skotare T and Sjögren R and Gouveia-Figueira S and Orikiiriza J and Bergström S and Normark J and Trygg J}, url = {https://pubs.rsc.org/en/content/articlepdf/2019/fd/c8fd00243f}, doi = {10.1177/1744987118824625}, year = {2019}, date = {2019-05-23}, journal = {Faraday Discussions}, volume = {218}, abstract = {Modern profiling technologies enable us to obtain large amounts of data which can be used later for a comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be carried out by bare analysis of separate data sets. Integrated approaches are necessary, because only data integration allows us to find correlation trends common for all studied data sets and reveal hidden structures not known a priori. This improves the understanding and interpretation of complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variations shared with other connected matrices and variations that are unique for each single matrix. Mapping unique variations is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for the integrated analysis of lipidomic, metabolomic and oxylipins data sets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, which makes the development of new diagnostic and prognostic tools, as well as a better understanding of the disease, of utmost importance. In the presented work, JUMBA made it possible to detect already known trends related to the disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced the complexity of the analysis and facilitated the detection of samples and variables corresponding to specific structures across multiple data sets, and by doing this enabled fast interpretation of the studied system. All of this makes JUMBA a perfect choice for multiblock analysis of systems biology data.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Modern profiling technologies enable us to obtain large amounts of data which can be used later for a comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be carried out by bare analysis of separate data sets. Integrated approaches are necessary, because only data integration allows us to find correlation trends common for all studied data sets and reveal hidden structures not known a priori. This improves the understanding and interpretation of complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variations shared with other connected matrices and variations that are unique for each single matrix. Mapping unique variations is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for the integrated analysis of lipidomic, metabolomic and oxylipins data sets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, which makes the development of new diagnostic and prognostic tools, as well as a better understanding of the disease, of utmost importance. In the presented work, JUMBA made it possible to detect already known trends related to the disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced the complexity of the analysis and facilitated the detection of samples and variables corresponding to specific structures across multiple data sets, and by doing this enabled fast interpretation of the studied system. All of this makes JUMBA a perfect choice for multiblock analysis of systems biology data. |
R, Kwizera; J, Musaazi; DB, Meya; W, Worodria; F, Bwanga; H, Kajumbula; SJ, Fowler; BJ, Kirenga; R, Gore; DW, Denning Burden of fungal asthma in Africa: A systematic review and meta-analysis Journal Article PloS One, 14 (5), 2019. @article{R2019, title = {Burden of fungal asthma in Africa: A systematic review and meta-analysis}, author = {Kwizera R and Musaazi J and Meya DB and Worodria W and Bwanga F and Kajumbula H and Fowler SJ and Kirenga BJ and Gore R and Denning DW}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521988/}, doi = {doi: 10.1371/journal.pone.0216568}, year = {2019}, date = {2019-05-16}, journal = {PloS One}, volume = {14}, number = {5}, abstract = {BACKGROUND: Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review. METHODS: We first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319. RESULTS: The IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3-52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6-21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children. CONCLUSION: There is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review. METHODS: We first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319. RESULTS: The IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3-52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6-21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children. CONCLUSION: There is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa. |
Y, Wibabara; C, Banura; J, Kalyango; C, Karamagi; A, Kityamuwesi; WC, Amia; P, Ocama Hepatitis B vaccination status and associated factors among undergraduate students of Makerere University College of Health Sciences. Journal Article Plose One, 14 (4), 2019. @article{Y2019, title = {Hepatitis B vaccination status and associated factors among undergraduate students of Makerere University College of Health Sciences.}, author = {Wibabara Y and Banura C and Kalyango J and Karamagi C and Kityamuwesi A and Amia WC and Ocama P}, doi = {10.1371/journal.pone.0214732}, year = {2019}, date = {2019-04-05}, journal = {Plose One}, volume = {14}, number = {4}, abstract = {BACKGROUND: Hepatitis B is a global health problem. Trainees in the health-related fields are exposed to occupational risk of Hepatitis B Virus. In Uganda, there is scarcity of information on vaccination among students in health-care. The objective of this study was to assess hepatitis B vaccination status of the students and factors associated. METHODS AND FINDINGS: This was a cross sectional study, conducted at Makerere University College of Health Sciences among undergraduate students who were eligible. A self-report on Hepatitis B vaccination status and various characteristics were collected on each participant, using a standardized structured self-administered questionnaire. Descriptive statistics were computed, bivariate and multivariate analysis were done using Stata 14. RESULTS: Out of 760 participants, 44.3% (95% CI 35.2-52.8) reported full vaccination. Vaccination was associated with gender, course, year of study and student's sponsorship. Males were less likely to be vaccinated, Prevalence Ratio (PR) 0.79; P-value <0.001, while self-sponsored students were also most likely to be vaccinated, PR 2.08; P-value <0.001. About 37% reported an accidental needle injury during their training. CONCLUSION: Full vaccination was low and given the high prevalence of needle injuries, it raises a safety concern. Vaccination should be mandatory for all students prior to clinical exposure. There is need for targeted interventions to increase uptake.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Hepatitis B is a global health problem. Trainees in the health-related fields are exposed to occupational risk of Hepatitis B Virus. In Uganda, there is scarcity of information on vaccination among students in health-care. The objective of this study was to assess hepatitis B vaccination status of the students and factors associated. METHODS AND FINDINGS: This was a cross sectional study, conducted at Makerere University College of Health Sciences among undergraduate students who were eligible. A self-report on Hepatitis B vaccination status and various characteristics were collected on each participant, using a standardized structured self-administered questionnaire. Descriptive statistics were computed, bivariate and multivariate analysis were done using Stata 14. RESULTS: Out of 760 participants, 44.3% (95% CI 35.2-52.8) reported full vaccination. Vaccination was associated with gender, course, year of study and student's sponsorship. Males were less likely to be vaccinated, Prevalence Ratio (PR) 0.79; P-value <0.001, while self-sponsored students were also most likely to be vaccinated, PR 2.08; P-value <0.001. About 37% reported an accidental needle injury during their training. CONCLUSION: Full vaccination was low and given the high prevalence of needle injuries, it raises a safety concern. Vaccination should be mandatory for all students prior to clinical exposure. There is need for targeted interventions to increase uptake. |
A, Baumann; J, Musaazi; A, Kambugu; M, Kälin; D, Weissberg; D, Ssemwanga; J, Fehr; B, Castelnuovo; C, Sekaggya-Wiltshire; A, Von Braun Journal of Acquired Immune Defficiency Syndrome , 80 (4), pp. 481-487, 2019. @article{A2019, title = {Virological outcome of patients with HIV drug resistance attending an urban out-patient clinic in Uganda: a need for structured adherence counselling and third line treatment options.}, author = {Baumann A and Musaazi J and Kambugu A and Kälin M and Weissberg D and Ssemwanga D and Fehr J and Castelnuovo B and Sekaggya-Wiltshire C and Von Braun A}, url = {https://journals.lww.com/jaids/Abstract/2019/04010/Virological_Outcome_of_Patients_With_HIV_Drug.15.aspx}, doi = {10.1097/QAI.0000000000001943}, year = {2019}, date = {2019-04-01}, journal = {Journal of Acquired Immune Defficiency Syndrome }, volume = {80}, number = {4}, pages = {481-487}, abstract = { Background: HIV drug resistance and suboptimal adherence are the main reasons for treatment failure among HIV-infected individuals. As genotypic resistance testing is not routinely available in resource-limited settings such as Uganda, data on transmitted and acquired resistance are sparse. Methods: This observational follow-up study assessed the virological outcomes of patients diagnosed with virological failure or transmitted HIV drug resistance in 2015 at the adults' outpatient clinic of the Infectious Diseases Institute in Kampala, Uganda. Initially, 2430 patients on antiretroviral therapy (ART) underwent virological monitoring, of which 190 had virological failure and were subsequently eligible for this follow-up study. Nine patients diagnosed with transmitted drug resistance were eligible. In patients with a viral load > 1000 copies/mL, genotypic resistance testing was performed. Results: Of 190 eligible patients, 30 (15.8%) had either died or were lost to follow-up. A total of 148 (77.9%) were included, of which 98 had had a change of ART regimen, and 50 had received adherence counseling only. The majority was now on second-line ART (N = 130, 87.8%). The median age was 39 years (interquartile range: 32–46), and 109 (73.6%) were women. Virological failure was diagnosed in 29 (19.6%) patients, of which 24 (82.8%) were on second-line ART. Relevant drug resistance was found in 25 (86.2%) cases, of which 12 (41.3%) carried dual and 7 (24.1%) triple drug resistance. Conclusion: Two years after initial virological failure, most patients followed up by this study had a successful virological outcome. However, a significant proportion either continued to fail or died or was lost to follow-up. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: HIV drug resistance and suboptimal adherence are the main reasons for treatment failure among HIV-infected individuals. As genotypic resistance testing is not routinely available in resource-limited settings such as Uganda, data on transmitted and acquired resistance are sparse. Methods: This observational follow-up study assessed the virological outcomes of patients diagnosed with virological failure or transmitted HIV drug resistance in 2015 at the adults' outpatient clinic of the Infectious Diseases Institute in Kampala, Uganda. Initially, 2430 patients on antiretroviral therapy (ART) underwent virological monitoring, of which 190 had virological failure and were subsequently eligible for this follow-up study. Nine patients diagnosed with transmitted drug resistance were eligible. In patients with a viral load > 1000 copies/mL, genotypic resistance testing was performed. Results: Of 190 eligible patients, 30 (15.8%) had either died or were lost to follow-up. A total of 148 (77.9%) were included, of which 98 had had a change of ART regimen, and 50 had received adherence counseling only. The majority was now on second-line ART (N = 130, 87.8%). The median age was 39 years (interquartile range: 32–46), and 109 (73.6%) were women. Virological failure was diagnosed in 29 (19.6%) patients, of which 24 (82.8%) were on second-line ART. Relevant drug resistance was found in 25 (86.2%) cases, of which 12 (41.3%) carried dual and 7 (24.1%) triple drug resistance. Conclusion: Two years after initial virological failure, most patients followed up by this study had a successful virological outcome. However, a significant proportion either continued to fail or died or was lost to follow-up. |
R, Nabatanzi; L, Bayigga; S, Cose; S, Rowland-Jones; G, Canderan; M, Joloba; D., Nakanjako Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort Journal Article Clinical Immunology, 201 , pp. 55-60, 2019. @article{R2019f, title = {Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort}, author = {Nabatanzi R and Bayigga L and Cose S and Rowland-Jones S and Canderan G and Joloba M and Nakanjako D.}, url = {https://www.sciencedirect.com/science/article/pii/S1521661619300221 }, doi = {https://doi.org/10.1016/j.clim.2019.02.010}, year = {2019}, date = {2019-04-01}, journal = {Clinical Immunology}, volume = {201}, pages = {55-60}, abstract = {Abstract Background We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community. Methods Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/−). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production. Results CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals. Conclusion NK cell activation and dysfunction persisted despite seven years of suppressive ART with “normalization” of peripheral CD4 counts. Previous article in issue Next article in issue Keywords Natural killer cells NK cell activation NK degranulation NK Cytolytic function NK cell dysfunction Antiretroviral therapy 107a Granzyme-B Interferon gamma NKG2D NKp46 Sub-Saharan Africa}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community. Methods Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/−). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production. Results CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals. Conclusion NK cell activation and dysfunction persisted despite seven years of suppressive ART with “normalization” of peripheral CD4 counts. Previous article in issue Next article in issue Keywords Natural killer cells NK cell activation NK degranulation NK Cytolytic function NK cell dysfunction Antiretroviral therapy 107a Granzyme-B Interferon gamma NKG2D NKp46 Sub-Saharan Africa |
S, Okoboi; A, Twimukye; O, Lazarus; B, Castelnuovo; C, Agaba; M, Immaculate; M, Nanfuka; A, Kambugu; R., King 2019. @online{S2019g, title = {Acceptability, perceived reliability and challenges associated with distributing HIV self‐test kits to young MSM in Uganda: a qualitative study}, author = {Okoboi S and Twimukye A and Lazarus O and Castelnuovo B and Agaba C and Immaculate M and Nanfuka M and Kambugu A and King R. }, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25269}, doi = {https://doi.org/10.1002/jia2.25269}, year = {2019}, date = {2019-04-01}, journal = {Journal of the International AIDS Society}, abstract = { Abstract Introduction HIV self‐testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self‐test (HIVST) to young men who have sex with men (MSM) in Uganda. Methods Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management. Results MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non‐painful; and non‐stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop‐in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services. Conclusions Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow‐up, linkage to HIV care and prevention services are needed for effective results. }, keywords = {}, pubstate = {published}, tppubtype = {online} } Abstract Introduction HIV self‐testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self‐test (HIVST) to young men who have sex with men (MSM) in Uganda. Methods Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management. Results MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non‐painful; and non‐stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop‐in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services. Conclusions Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow‐up, linkage to HIV care and prevention services are needed for effective results. |
C, Sekaggya-Wiltshire; M, Chirehwa; J, Musaazi; von A, Braun; A, Buzibye; D, Muller; U, Gutteck; I, Motta; A, Calcagno; JS, Fehr; A, Kambugu; B, Castelnuovo; M, Lamorde; P, Denti Low anti-tuberculosis drug concentrations in HIV-Tuberculosis co-infected adults with low body weight; is it time to update dosing guidelines? Journal Article American society for Microbiology , 2019. @article{C2019b, title = {Low anti-tuberculosis drug concentrations in HIV-Tuberculosis co-infected adults with low body weight; is it time to update dosing guidelines?}, author = {Sekaggya-Wiltshire C and Chirehwa M and Musaazi J and von Braun A and Buzibye A and Muller D and Gutteck U and Motta I and Calcagno A and Fehr JS and Kambugu A and Castelnuovo B and Lamorde M and Denti P}, url = {https://aac.asm.org/content/63/6/e02174-18}, doi = {10.1128/AAC.02174-18}, year = {2019}, date = {2019-03-25}, journal = {American society for Microbiology }, abstract = {ntituberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors, including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations. HIV-infected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 h after drug intake) 2, 8, and 24 weeks after treatment initiation. Between May 2013 and November 2015, we enrolled 268 patients (148 males) with a median weight of 53.5 (interquartile range [IQR], 47.5 to 59.0) kg and a median age of 35 (IQR, 29 to 40) years. Population pharmacokinetic modeling was used to interpret the data and revealed that patients weighing <55 kg achieved lower concentrations than those in higher weight bands for all drugs in the regimen. The models predicted that this imbalance could be solved with a dose increment of one fixed-dose combination (FDC) tablet for the weight bands of 30 to 37 and 38 to 54 kg. Additionally, the concomitant use of efavirenz increased isoniazid clearance by 24.1%, while bioavailability and absorption of rifampin and isoniazid varied up to 30% in patients on different formulations. Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to current weight band-based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently used drug formulations of anti-TB drugs. (This study has been registered at ClinicalTrials.gov under identifier NCT01782950.)}, keywords = {}, pubstate = {published}, tppubtype = {article} } ntituberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors, including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations. HIV-infected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 h after drug intake) 2, 8, and 24 weeks after treatment initiation. Between May 2013 and November 2015, we enrolled 268 patients (148 males) with a median weight of 53.5 (interquartile range [IQR], 47.5 to 59.0) kg and a median age of 35 (IQR, 29 to 40) years. Population pharmacokinetic modeling was used to interpret the data and revealed that patients weighing <55 kg achieved lower concentrations than those in higher weight bands for all drugs in the regimen. The models predicted that this imbalance could be solved with a dose increment of one fixed-dose combination (FDC) tablet for the weight bands of 30 to 37 and 38 to 54 kg. Additionally, the concomitant use of efavirenz increased isoniazid clearance by 24.1%, while bioavailability and absorption of rifampin and isoniazid varied up to 30% in patients on different formulations. Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to current weight band-based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently used drug formulations of anti-TB drugs. (This study has been registered at ClinicalTrials.gov under identifier NCT01782950.) |
EAO, Laker; MS, Nabaggala; A, Kaimal; D, Nalwanga; B, Castelnuovo; A, Musubire; A, Kiragga; M, Lamorde; RP, Ratanshi BMC Infectious Diseases, 19 (1), pp. p.280, 2019. @article{EAO2019, title = { An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir}, author = {Laker EAO and Nabaggala MS and Kaimal A and Nalwanga D and Castelnuovo B and Musubire A and Kiragga A and Lamorde M and Ratanshi RP}, url = {https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-3907-5}, doi = {10.1186/s12879-019-3907-5}, year = {2019}, date = {2019-03-25}, journal = {BMC Infectious Diseases}, volume = {19}, number = {1}, pages = {p.280}, abstract = {Background The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. Methods This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. Results Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). Conclusions Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. Methods This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. Results Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). Conclusions Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir. |
Nasuuna, Esther; Babirye, Lillian; Namimbi, Florence; Muganzi, Alex; Kigozi, Joanita Open Journal of Pediatrics and Neonatal care , 2019. @article{Nasuuna2019, title = {Where are the HIV Positive Children? A Comparison of Facility and Community Testing Approaches in 14 Public Health Facilities in Five Ugandan Districts.}, author = {Esther Nasuuna and Lillian Babirye and Florence Namimbi and Alex Muganzi and Joanita Kigozi}, url = {https://www.idi-makerere.com/wp-content/uploads/2019/08/OJPNC-ID25-1.pdf}, year = {2019}, date = {2019-03-25}, journal = {Open Journal of Pediatrics and Neonatal care }, keywords = {}, pubstate = {published}, tppubtype = {article} } |
MK, Shenoy; DW, Fadrosh; DL, Lin; W, Worodria; P, Byanyima; E, Musisi; S, Kaswabuli; J, Zawedde; I, Sanyu; E, Chang; S, Fong; K, McCauley; JL, Davis; L, Huang; SV, Lynch Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction Journal Article Microbiome, 7 (1), 2019. @article{MK2019, title = {Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction}, author = {Shenoy MK and Fadrosh DW and Lin DL and Worodria W and Byanyima P and Musisi E and Kaswabuli S and Zawedde J and Sanyu I and Chang E and Fong S and McCauley K and Davis JL and Huang L and Lynch SV}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413461/}, doi = {10.1186/s40168-019-0651-4}, year = {2019}, date = {2019-03-11}, journal = {Microbiome}, volume = {7}, number = {1}, abstract = {Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia. |
E, Nasuuna; J, Kigozi; PA, Muwanguzi; J, Babirye; L, Kiwala; A, Muganzi; N, Sewankambo; D, Nakanjako Challenges faced by caregivers of virally non-suppressed children on the intensive adherence counselling program in Uganda: a qualitative study Journal Article BMC Health Services Research , 19 (1), 2019. @article{E2019e, title = {Challenges faced by caregivers of virally non-suppressed children on the intensive adherence counselling program in Uganda: a qualitative study}, author = {Nasuuna E and Kigozi J and Muwanguzi PA and Babirye J and Kiwala L and Muganzi A and Sewankambo N and Nakanjako D}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407183/pdf/12913_2019_Article_3963.pdf}, doi = {10.1186/s12913-019-3963-y}, year = {2019}, date = {2019-03-07}, journal = {BMC Health Services Research }, volume = {19}, number = {1}, abstract = {Background Of the estimated 130,000 children living with HIV in Uganda, 47% are receiving ART. Only 39.3% have suppressed HIV-1 viral load to levels below 50 copies per ml. Caregivers are key drivers of adherence to achieve viral suppression in children. We investigated the challenges and potential support required by caregivers of ART-treated children. Methods A qualitative study was conducted within the Infectious Diseases Institute paediatric ART program in Kampala and Hoima districts. Caregivers of children with viral loads above 1000 copies were purposively sampled and engaged in five focus group discussions (FGD). The FGD guide highlighted questions on challenges that caregivers face and the kind of support they required to improve children’s ART adherence. Thematic analysis using the inductive approach was used. All the transcripts were read, coded and emergent themes determined. Results Overall, 37 caregivers participated in five FGD, of whom 29 (78%) were female, 28 (76%) were HIV-infected and 25 (68%) were biological parents of the children. The elicited challenges were either in failure to attend the counselling sessions or in supporting adherence to medication. Individual and health system challenges such as competing priorities, logistics, poor quality of counselling and lack of reminders prevented attendance at counselling sessions. Five themes emerged as challenges to supporting adherence: i) environmental (school activities, working away from home), ii) personal (non-disclosure, stigma), iii) psychological (guilt), iv) financial (lack of food and transport) and v) child-related (fatigue and peer influence). Three major themes emerged for the support that caregivers needed namely: a) health system reforms (clinic appointments outside school hours, minimize ART drug stock outs and improve quality of counselling), b) psychosocial support (support with disclosure of HIV status to children and their families, more frequent peer support groups and parenting classes) and c) economic empowerment (training in vocational skills, school fees support and opportunities to initiate income generating activities). Discussion and conclusion To achieve viral suppression, ART programs require targeted efforts to provide specific health facility requirements, psychological and economic needs of ART-treated children and their caregivers. Integration of HIV treatment with programs for orphans and vulnerable children may improve viral suppression rates. Keywords: Caregivers, Adherence counselling, Paediatric HIV, Adolescent, Viral suppression}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Of the estimated 130,000 children living with HIV in Uganda, 47% are receiving ART. Only 39.3% have suppressed HIV-1 viral load to levels below 50 copies per ml. Caregivers are key drivers of adherence to achieve viral suppression in children. We investigated the challenges and potential support required by caregivers of ART-treated children. Methods A qualitative study was conducted within the Infectious Diseases Institute paediatric ART program in Kampala and Hoima districts. Caregivers of children with viral loads above 1000 copies were purposively sampled and engaged in five focus group discussions (FGD). The FGD guide highlighted questions on challenges that caregivers face and the kind of support they required to improve children’s ART adherence. Thematic analysis using the inductive approach was used. All the transcripts were read, coded and emergent themes determined. Results Overall, 37 caregivers participated in five FGD, of whom 29 (78%) were female, 28 (76%) were HIV-infected and 25 (68%) were biological parents of the children. The elicited challenges were either in failure to attend the counselling sessions or in supporting adherence to medication. Individual and health system challenges such as competing priorities, logistics, poor quality of counselling and lack of reminders prevented attendance at counselling sessions. Five themes emerged as challenges to supporting adherence: i) environmental (school activities, working away from home), ii) personal (non-disclosure, stigma), iii) psychological (guilt), iv) financial (lack of food and transport) and v) child-related (fatigue and peer influence). Three major themes emerged for the support that caregivers needed namely: a) health system reforms (clinic appointments outside school hours, minimize ART drug stock outs and improve quality of counselling), b) psychosocial support (support with disclosure of HIV status to children and their families, more frequent peer support groups and parenting classes) and c) economic empowerment (training in vocational skills, school fees support and opportunities to initiate income generating activities). Discussion and conclusion To achieve viral suppression, ART programs require targeted efforts to provide specific health facility requirements, psychological and economic needs of ART-treated children and their caregivers. Integration of HIV treatment with programs for orphans and vulnerable children may improve viral suppression rates. Keywords: Caregivers, Adherence counselling, Paediatric HIV, Adolescent, Viral suppression |
D, Kibirige; RE, Sanya; R, Nantanda; W, Worodria; B, Kirenga Allergy, Arthma and Clinical Immunology , 15 (1), 2019. @article{D2019, title = {Availability and affordability of medicines and diagnostic tests recommended for management of asthma and chronic obstructive pulmonary disease in sub-Saharan Africa: a systematic review}, author = {Kibirige D and Sanya RE and Nantanda R and Worodria W and Kirenga B}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407228/}, doi = {10.1186/s13223-019-0329-2}, year = {2019}, date = {2019-03-07}, journal = {Allergy, Arthma and Clinical Immunology }, volume = {15}, number = {1}, abstract = {Background: Early accurate diagnosis and sustainable availability of affordable medicines and diagnostic tests is fundamental in optimal management of asthma and chronic obstructive pulmonary disease (COPD). We systematically reviewed original research articles about availability and affordability of medicines and diagnostic tests recommended for management of asthma and COPD in sub-Saharan Africa (SSA). Methods: We searched PubMed, Scopus and African Journal Online for original research articles conducted in SSA between 2000 and March 2018 containing information about availability and affordability of any recommended medicine and diagnostic test for asthma and COPD. Results: The search yielded 9 eligible research articles. Availability of short-acting beta agonists (SABA), inhaled corticosteroids (ICS) and short acting anti-muscarinic agents (SAMA) ranged between 19.9-100%, 0-45.5% and 0-14.3% respectively. Combination of ICS-long acting beta agonists (LABA) were available in 0-14.3% of facilities surveyed. There was absence of inhaled long acting anti-muscarinic agents (LAMA) and LAMA/LABA combinations. Spirometry and peak expiratory flow devices were available in 24.4-29.4% and 6.7-53.6% respectively. Affordability of SABA and ICS varied greatly, ranging from < 2 to 107 days' wages while ICS-LABA combinations, SAMA and oral theophylline plus leukotriene receptor antagonists cost 6.4-17.1, 13.7 and 6.9 days' wages respectively. Conclusion: Availability and affordability of medicines and diagnostics recommended for the management of asthma and COPD is a big challenge in SSA. Research about this subject in this region is still limited. More robustly performed studies are required to further understand the magnitude of inequity in access to these medicines and diagnostic tests in SSA and also to formulate simple pragmatic solutions to address this challenge.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Early accurate diagnosis and sustainable availability of affordable medicines and diagnostic tests is fundamental in optimal management of asthma and chronic obstructive pulmonary disease (COPD). We systematically reviewed original research articles about availability and affordability of medicines and diagnostic tests recommended for management of asthma and COPD in sub-Saharan Africa (SSA). Methods: We searched PubMed, Scopus and African Journal Online for original research articles conducted in SSA between 2000 and March 2018 containing information about availability and affordability of any recommended medicine and diagnostic test for asthma and COPD. Results: The search yielded 9 eligible research articles. Availability of short-acting beta agonists (SABA), inhaled corticosteroids (ICS) and short acting anti-muscarinic agents (SAMA) ranged between 19.9-100%, 0-45.5% and 0-14.3% respectively. Combination of ICS-long acting beta agonists (LABA) were available in 0-14.3% of facilities surveyed. There was absence of inhaled long acting anti-muscarinic agents (LAMA) and LAMA/LABA combinations. Spirometry and peak expiratory flow devices were available in 24.4-29.4% and 6.7-53.6% respectively. Affordability of SABA and ICS varied greatly, ranging from < 2 to 107 days' wages while ICS-LABA combinations, SAMA and oral theophylline plus leukotriene receptor antagonists cost 6.4-17.1, 13.7 and 6.9 days' wages respectively. Conclusion: Availability and affordability of medicines and diagnostics recommended for the management of asthma and COPD is a big challenge in SSA. Research about this subject in this region is still limited. More robustly performed studies are required to further understand the magnitude of inequity in access to these medicines and diagnostic tests in SSA and also to formulate simple pragmatic solutions to address this challenge. |
RR, Atherton; FV, Cresswell; J, Ellis; SB, Kitaka; DR., Boulware Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary. Journal Article Frontiers in Pediatrics, 2019. @article{RR2019, title = {Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary.}, author = {Atherton RR and Cresswell FV and Ellis J and Kitaka SB and Boulware DR. }, url = {https://www.frontiersin.org/articles/10.3389/fped.2019.00034/full#h1}, doi = {doi.org/10.3389/fped.2019.00034}, year = {2019}, date = {2019-02-28}, journal = {Frontiers in Pediatrics}, abstract = {Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children. |
A, Calcagno; J, Cusato; C, Sekaggya-Wiltshire; von A, Braun; I, Motta; G, Turyasingura; B, Castelnuovo; J, Fehr; G, Di Perri; M, Lamorde The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study. Journal Article Clinical Pharmacology & Therapeutics , 106 (2), pp. 450-457, 2019. @article{A2019b, title = {The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study. }, author = {Calcagno A and Cusato J and Sekaggya-Wiltshire C and von Braun A and Motta I and Turyasingura G and Castelnuovo B and Fehr J and Di Perri G and Lamorde M}, url = {https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1403}, doi = {doi.org/10.1002/cpt.1403}, year = {2019}, date = {2019-02-19}, journal = {Clinical Pharmacology & Therapeutics }, volume = {106}, number = {2}, pages = {450-457}, abstract = {Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The aim of this study was to assess the influence of single‐nucleotide polymorphisms (SNPs) in genes encoding for proteins involved in antitubercular drug disposition or effect. A pharmacogenetic study was conducted in Kampala, Uganda, where all analysis was performed. The impact of SNPs on antitubercular drug exposure, adverse events, and treatment outcomes was evaluated in patients coinfected with HIV/TB receiving treatments for both conditions. In 221 participants, N‐acetyltransferase 2 (NAT2; rs1799930), solute carrier organic anion transporter family member 1B1 (SLCO1B1; rs4149032), and pregnane X receptor (PXR; rs2472677) variants affected isoniazid exposure in multivariate analysis. Most patients were deemed cured (163; 73.8%), yet PXR 63396TT carriers had a higher probability of death (P = 0.007) and of worsening peripheral neuropathy (P = 0.018). In this exploratory study in Ugandan patients coinfected with HIV/TB, genetic variants in PXR, SLCO1B1, and NAT2 were moderately associated with isoniazid exposure, whereas PXR 63396TT carriers showed worse outcomes. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The aim of this study was to assess the influence of single‐nucleotide polymorphisms (SNPs) in genes encoding for proteins involved in antitubercular drug disposition or effect. A pharmacogenetic study was conducted in Kampala, Uganda, where all analysis was performed. The impact of SNPs on antitubercular drug exposure, adverse events, and treatment outcomes was evaluated in patients coinfected with HIV/TB receiving treatments for both conditions. In 221 participants, N‐acetyltransferase 2 (NAT2; rs1799930), solute carrier organic anion transporter family member 1B1 (SLCO1B1; rs4149032), and pregnane X receptor (PXR; rs2472677) variants affected isoniazid exposure in multivariate analysis. Most patients were deemed cured (163; 73.8%), yet PXR 63396TT carriers had a higher probability of death (P = 0.007) and of worsening peripheral neuropathy (P = 0.018). In this exploratory study in Ugandan patients coinfected with HIV/TB, genetic variants in PXR, SLCO1B1, and NAT2 were moderately associated with isoniazid exposure, whereas PXR 63396TT carriers showed worse outcomes. |
K, Ssebambulidde; I, Segawa; E, Laker; M, Lamorde; B, Castelnouvo; N, Nakasujja; A, Calcagno Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda Journal Article Oxford Medical case Reports , 2019 (2), 2019. @article{K2019b, title = {Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda}, author = {Ssebambulidde K and Segawa I and Laker E and Lamorde M and Castelnouvo B and Nakasujja N and Calcagno A}, url = {https://academic.oup.com/omcr/article/2019/2/omy132/5321215}, doi = {10.1093/omcr/omy132}, year = {2019}, date = {2019-02-16}, journal = {Oxford Medical case Reports }, volume = {2019}, number = {2}, 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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. |
MO, Kuteesa; M, Quaife; S, Biraro; KR, Katumba; J, Seeley; A, Kamali; D., Nakanjako AIDS and Behavior , 2019. @article{MO2019, title = {Acceptability and Predictors of Uptake of Anti-retroviral Pre-exposure Prophylaxis (PrEP) Among Fishing Communities in Uganda: A Cross-Sectional Discrete Choice Experiment Survey}, author = {Kuteesa MO and Quaife M and Biraro S and Katumba KR and Seeley J and Kamali A and Nakanjako D. }, url = {https://link.springer.com/article/10.1007%2Fs10461-019-02418-7}, doi = {10.1007/s10461-019-02418-7}, year = {2019}, date = {2019-02-08}, journal = {AIDS and Behavior }, abstract = {We used a discrete choice experiment to assess the acceptability and potential uptake of HIV pre-exposure prophylaxis (PrEP) among 713 HIV-negative members of fishing communities in Uganda. Participants were asked to choose between oral pill, injection, implant, condoms, vaginal ring (women), and men circumcision. Product attributes were HIV prevention effectiveness, sexually transmitted infection (STI) prevention, contraception, waiting time, and secrecy of use. Data were analysed using mixed multinomial logit and latent class models. HIV prevention effectiveness was viewed as the most important attribute. Both genders preferred oral PrEP. Women least preferred the vaginal ring and men the implant. Condom use was predicted to decrease by one third among men, and not to change amongst women. Oral PrEP and other new prevention technologies are acceptable among fishing communities and may have substantial demand. Future work should explore utility of multiple product technologies that combine contraception with HIV and other STI prevention.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We used a discrete choice experiment to assess the acceptability and potential uptake of HIV pre-exposure prophylaxis (PrEP) among 713 HIV-negative members of fishing communities in Uganda. Participants were asked to choose between oral pill, injection, implant, condoms, vaginal ring (women), and men circumcision. Product attributes were HIV prevention effectiveness, sexually transmitted infection (STI) prevention, contraception, waiting time, and secrecy of use. Data were analysed using mixed multinomial logit and latent class models. HIV prevention effectiveness was viewed as the most important attribute. Both genders preferred oral PrEP. Women least preferred the vaginal ring and men the implant. Condom use was predicted to decrease by one third among men, and not to change amongst women. Oral PrEP and other new prevention technologies are acceptable among fishing communities and may have substantial demand. Future work should explore utility of multiple product technologies that combine contraception with HIV and other STI prevention. |
E, Nakku-Joloba; Kiguli, ; CN, Kayemba J; A, Twimukye; JK, Mbazira; R, Parkes-Ratanshi; M, Birungi; J, Kyenkya; J, Byamugisha; C, Gaydos; YC, Manabe BMC Infectious Diseases, 19 (1), pp. 124, 2019. @article{E2019d, title = {Perspectives on male partner notification and treatment for syphilis among antenatal women and their partners in Kampala and Wakiso districts, Uganda}, author = {Nakku-Joloba E and Kiguli and J Kayemba CN and Twimukye A and Mbazira JK and Parkes-Ratanshi R and Birungi M and Kyenkya J and Byamugisha J and Gaydos C and Manabe YC}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366113/}, doi = {10.1186/s12879-019-3695-y.}, year = {2019}, date = {2019-02-06}, journal = {BMC Infectious Diseases}, volume = {19}, number = {1}, pages = {124}, abstract = {BACKGROUND: Syphilis screening can be successfully integrated into antenatal clinics, and potentially avert significant morbidity and mortality to unborn infants. A minority of male partners report for testing and treatment, increasing the likelihood of reinfection. We conducted a qualitative study to understand factors influencing male partners to seek treatment after syphilis notification by their pregnant partners. METHODS: A purposeful sample of 54 adults who participated in the STOP (Syphilis Treatment of Partners) study was stratified by gender (24 women, 30 male partners) and enrolled for in-depth interviews which were audio recorded, transcribed, and analyzed using the thematic approach. RESULTS: The participants' median age (IQR) was 32 years (25-44), 87% were married, and 57.4% (31/74) had attained secondary education. Fourteen of 22 (63%) female participants reported that they sometimes experienced domestic violence. Male participant's knowledge of syphilis and their perception of their valued role as responsible fathers of an unborn baby facilitated return. Female's fear of partner's violence and poor communication between partners, were barriers against delivery of the notification forms to partners and subsequent treatment of partners. For men, fear of injection pain, perceptions of syphilis as a genetic disease and as a woman's problem, busy work schedules, poor access to good STD services, shared facilities with women in clinics, as well as HIV-related stigma were important barrier factors. CONCLUSIONS: The return to the clinic for treatment of male partners after partner notification by infected pregnant women, was low due to limited knowledge about syphilis, fear of painful injection, fears of domestic violence, lack of communication skills (individual characteristics) and syphilis disease characteristics such as signs and symptoms. This, combined with health services characteristics such as structural barriers that hinder male partner treatment, low access, low capacity, work/time challenges, inadequate laboratory services and low clinic personnel capacity; threatens efforts to eliminate mother-to-child infection of syphilis. Improved public messaging about syphilis, better services, legal and policy frameworks supporting STD notification and treatment in resource-constrained settings are needed for effective STD control.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Syphilis screening can be successfully integrated into antenatal clinics, and potentially avert significant morbidity and mortality to unborn infants. A minority of male partners report for testing and treatment, increasing the likelihood of reinfection. We conducted a qualitative study to understand factors influencing male partners to seek treatment after syphilis notification by their pregnant partners. METHODS: A purposeful sample of 54 adults who participated in the STOP (Syphilis Treatment of Partners) study was stratified by gender (24 women, 30 male partners) and enrolled for in-depth interviews which were audio recorded, transcribed, and analyzed using the thematic approach. RESULTS: The participants' median age (IQR) was 32 years (25-44), 87% were married, and 57.4% (31/74) had attained secondary education. Fourteen of 22 (63%) female participants reported that they sometimes experienced domestic violence. Male participant's knowledge of syphilis and their perception of their valued role as responsible fathers of an unborn baby facilitated return. Female's fear of partner's violence and poor communication between partners, were barriers against delivery of the notification forms to partners and subsequent treatment of partners. For men, fear of injection pain, perceptions of syphilis as a genetic disease and as a woman's problem, busy work schedules, poor access to good STD services, shared facilities with women in clinics, as well as HIV-related stigma were important barrier factors. CONCLUSIONS: The return to the clinic for treatment of male partners after partner notification by infected pregnant women, was low due to limited knowledge about syphilis, fear of painful injection, fears of domestic violence, lack of communication skills (individual characteristics) and syphilis disease characteristics such as signs and symptoms. This, combined with health services characteristics such as structural barriers that hinder male partner treatment, low access, low capacity, work/time challenges, inadequate laboratory services and low clinic personnel capacity; threatens efforts to eliminate mother-to-child infection of syphilis. Improved public messaging about syphilis, better services, legal and policy frameworks supporting STD notification and treatment in resource-constrained settings are needed for effective STD control. |
WDF, Venter; A, Kambugu; MF, Chersich; S, Becker; A, Hill; N, Arulappan; M, Moorhouse; M, Majam; G, Akpomiemie; S, Sokhela; S, Poongulali; C, Feldman; C, Duncombe; DHB, Ripin; A, Vos; N, Kumarasamy Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial Journal Article Journal of Acquired Immune Defficiency Syndrome (1999), 80 (2), pp. 224–233., 2019. @article{WDF2019, title = {Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial}, author = {Venter WDF and Kambugu A and Chersich MF and Becker S and Hill A and Arulappan N and Moorhouse M and Majam M and Akpomiemie G and Sokhela S and Poongulali S and Feldman C and Duncombe C and Ripin DHB and Vos A and Kumarasamy N}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358196/}, doi = {10.1097/QAI.0000000000001908}, year = {2019}, date = {2019-02-01}, journal = {Journal of Acquired Immune Defficiency Syndrome (1999)}, volume = {80}, number = {2}, pages = {224–233.}, abstract = {Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF). Setting: HIV-1–infected treatment-naive adults in India, South Africa, and Uganda. Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772). Results: Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = −1.49%, 95% CI: −6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF. Conclusions: Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation. Key Words: tenofovir, stavudine DEXA, HIV, India, renal, South Africa, toxicity, trial, Uganda, dose reduction, resource allocation, public health}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF). Setting: HIV-1–infected treatment-naive adults in India, South Africa, and Uganda. Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772). Results: Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = −1.49%, 95% CI: −6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF. Conclusions: Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation. Key Words: tenofovir, stavudine DEXA, HIV, India, renal, South Africa, toxicity, trial, Uganda, dose reduction, resource allocation, public health |
WDF, Venter; A, Kambugu; MF, Chersich; S, Becker; A, Hill; N, Arulappan; M, Moorhouse; M, Majam; G, Akpomiemie; S, Sokhela; S, Poongulali; C, Feldman; C, Duncombe; DHB, Ripin; A, Vos; N., Kumarasamy Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial Journal Article Journal of Acquired Immune Deficiency Syndromes, 80 (1), pp. 224-233, 2019. @article{WDF2019b, title = {Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial}, author = {Venter WDF and Kambugu A and Chersich MF and Becker S and Hill A and Arulappan N and Moorhouse M and Majam M and Akpomiemie G and Sokhela S and Poongulali S and Feldman C and Duncombe C and Ripin DHB and Vos A and Kumarasamy N. }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358196/}, doi = { doi: 10.1097/QAI.0000000000001908}, year = {2019}, date = {2019-02-01}, journal = {Journal of Acquired Immune Deficiency Syndromes}, volume = {80}, number = {1}, pages = {224-233}, abstract = {Abstract Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF). Setting: HIV-1–infected treatment-naive adults in India, South Africa, and Uganda. Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772). Results: Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = −1.49%, 95% CI: −6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF. Conclusions: Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation. Key Words: tenofovir, stavudine DEXA, HIV, India, renal, South Africa, toxicity, trial, Uganda, dose reduction, resource allocation, public health}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF). Setting: HIV-1–infected treatment-naive adults in India, South Africa, and Uganda. Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772). Results: Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = −1.49%, 95% CI: −6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF. Conclusions: Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation. Key Words: tenofovir, stavudine DEXA, HIV, India, renal, South Africa, toxicity, trial, Uganda, dose reduction, resource allocation, public health |
R, Rajasingham; DB, Meya; GS, Greene; A, Jordan; M, Nakawuka; TM, Chiller; DR, Boulware; BA, Larson Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis. Journal Article PloS One, 14 (1), 2019. @article{R2019b, title = {Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis.}, author = {Rajasingham R and Meya DB and Greene GS and Jordan A and Nakawuka M and Chiller TM and Boulware DR and Larson BA}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328136/}, doi = {10.1371/journal.pone.0210105}, year = {2019}, date = {2019-01-29}, journal = {PloS One}, volume = {14}, number = {1}, abstract = {BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective. |
K, Jessie; Peter, Edwards; Freddie, Arimi; Grace, Ssengooba; Milissa, Mulholland; A, Markiewicz Elizabeth; T, Bukusi Judy; Arti, Orikiiriza; Weir., Virkud Sharon The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas Journal Article Journal of International AIDS society , 22 (1), 2019. @article{K2019, title = {The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas}, author = {Jessie K and Edwards Peter and Arimi Freddie and Ssengooba Grace and Mulholland Milissa and Markiewicz Elizabeth A and Bukusi Judy T and Orikiiriza Arti and Virkud Sharon Weir. }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344908/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344908/}, doi = {10.1002/jia2.25226}, year = {2019}, date = {2019-01-24}, journal = {Journal of International AIDS society }, volume = {22}, number = {1}, abstract = {INTRODUCTION: HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed. METHODS: Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas. RESULTS: Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93). CONCLUSIONS: People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed. METHODS: Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas. RESULTS: Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93). CONCLUSIONS: People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment. |
JK, Edwards; P, Arimi; F, Ssengooba; G, Mulholland; M, Markiewicz; EA, Bukusi; JT, Orikiiriza; A, Virkud; S., Weir The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas Journal Article Journal of the International AIDS Society, 22 (1), 2019. @article{JK2019, title = {The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas}, author = {Edwards JK and Arimi P and Ssengooba F and Mulholland G and Markiewicz M and Bukusi EA and Orikiiriza JT and Virkud A and Weir S. }, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25226}, doi = { https://doi.org/10.1002/jia2.25226}, year = {2019}, date = {2019-01-24}, journal = {Journal of the International AIDS Society}, volume = {22}, number = {1}, abstract = { Abstract Introduction HIV care and treatment in cross‐border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross‐border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed. Methods Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non‐residents found in those areas. Results Overall, 43% of participants with HIV found in cross‐border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non‐resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93). Conclusions People living in or travelling through cross‐border areas may face barriers in learning their HIV status. Moreover, while non‐residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Introduction HIV care and treatment in cross‐border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross‐border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed. Methods Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non‐residents found in those areas. Results Overall, 43% of participants with HIV found in cross‐border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non‐resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93). Conclusions People living in or travelling through cross‐border areas may face barriers in learning their HIV status. Moreover, while non‐residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment. |
AN, Kiragga; F, Mubiru; AD, Kambugu; MR, Kamya; B, Castelnuovo A decade ofantiretroviral therapy in Uganda: what are the emerging causes of death? Journal Article BMC Infectious Diseases, 19 (77), 2019. @article{AN2019, title = {A decade ofantiretroviral therapy in Uganda: what are the emerging causes of death? }, author = {Kiragga AN and Mubiru F and Kambugu AD and Kamya MR and Castelnuovo B}, url = {https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-3724-x}, doi = {10.1186/s12879-019-3724-x. }, year = {2019}, date = {2019-01-21}, journal = {BMC Infectious Diseases}, volume = {19}, number = {77}, abstract = {Background The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa. Methods We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death. Results Of the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%). Conclusion Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa. Methods We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death. Results Of the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%). Conclusion Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases. |
S, Okoboi; B, Castelnuovo; DM, Moore; J, Musaazi; A, Kambugu; J, Birungi; M, Nanfuka; A, Van Rie BMC Public Health, 19 (87), 2019. @article{S2019d, title = {Incidence rate of sexually transmitted infections among HIV infected patients on long-term ART in an urban and a rural clinic in Uganda. BMC Public Health}, author = {Okoboi S and Castelnuovo B and Moore DM and Musaazi J and Kambugu A and Birungi J and Nanfuka M and Van Rie A}, url = {https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-6417-x}, doi = {10.1186/s12889-019-6417-x}, year = {2019}, date = {2019-01-18}, journal = {BMC Public Health}, volume = {19}, number = {87}, abstract = {HIV immunosuppression increases susceptibility to other STIs and STIs can enhance HIV transmission, reduce CD4 cell count and increase viral load. Co-infections of HIV and STIs may thus reduce the preventive benefits of ART. Little is known about the incidence rate of STIs among long-term patients on ART. Method We conducted a secondary data analysis of all patients enrolled in a rural and an urban longitudinal cohort studies who initiated ART between April 2003 and July 2007 followed up to 2016. Patients were screened for STI every three months using “a syndromic and case management approaches”. STI incidence rate, was defined as the number of new cases per population at risk over the follow-up review period. We performed a time-to-event and Kaplan Meier analysis. We used a multivariable Cox proportional hazards regression model to assess for factors associated with STI incidence. Result Of 1012 participants, 402 (39.8%) were urban and 610 (60.2%) rural residents. Mean age was 42.8 years (SD 8.5). The total number of follow up time was 44,304 person years. We observed STI incidence rate of 2.1 per 1000 person-years after follow-up. Rural residence (adjusted hazard ratio [aHR] 3.53, 95% CI: 1.95–6.39), younger age (aHR 2.05, 95% CI: 1.02–4.12 for 18–34 years and aHR 1.65, 95% CI: 1.00–2.72 for 35–44 years) were factors associated with higher incidence of STIs. Being male (aHR 0.51, 95% CI: 0.27–0.93) was associated with a lower incidence of STIs. Conclusion We found STIs incidence rate of approximately 3 per 1000 person-years among patients on long-term (≥ 4 years) ART followed up-to 3.5 years. Rural and younger persons on ART should be routinely screened for STIs because high incidence of STIs may undo the preventative effects of ART for all.}, keywords = {}, pubstate = {published}, tppubtype = {article} } HIV immunosuppression increases susceptibility to other STIs and STIs can enhance HIV transmission, reduce CD4 cell count and increase viral load. Co-infections of HIV and STIs may thus reduce the preventive benefits of ART. Little is known about the incidence rate of STIs among long-term patients on ART. Method We conducted a secondary data analysis of all patients enrolled in a rural and an urban longitudinal cohort studies who initiated ART between April 2003 and July 2007 followed up to 2016. Patients were screened for STI every three months using “a syndromic and case management approaches”. STI incidence rate, was defined as the number of new cases per population at risk over the follow-up review period. We performed a time-to-event and Kaplan Meier analysis. We used a multivariable Cox proportional hazards regression model to assess for factors associated with STI incidence. Result Of 1012 participants, 402 (39.8%) were urban and 610 (60.2%) rural residents. Mean age was 42.8 years (SD 8.5). The total number of follow up time was 44,304 person years. We observed STI incidence rate of 2.1 per 1000 person-years after follow-up. Rural residence (adjusted hazard ratio [aHR] 3.53, 95% CI: 1.95–6.39), younger age (aHR 2.05, 95% CI: 1.02–4.12 for 18–34 years and aHR 1.65, 95% CI: 1.00–2.72 for 35–44 years) were factors associated with higher incidence of STIs. Being male (aHR 0.51, 95% CI: 0.27–0.93) was associated with a lower incidence of STIs. Conclusion We found STIs incidence rate of approximately 3 per 1000 person-years among patients on long-term (≥ 4 years) ART followed up-to 3.5 years. Rural and younger persons on ART should be routinely screened for STIs because high incidence of STIs may undo the preventative effects of ART for all. |
E, Nakku-Joloba; EE, Pisarski; MA, Wyatt; TR, Muwonge; S, Asiimwe; CL, Celum; JM, Baeten; ET, Katabira; NC., Ware Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples. Journal Article Journal of the International AIDS Society, 2019. @article{E2019f, title = {Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples. }, author = {Nakku-Joloba E and Pisarski EE and Wyatt MA and Muwonge TR and Asiimwe S and Celum CL and Baeten JM and Katabira ET and Ware NC. }, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25225}, doi = { https://doi.org/10.1002/jia2.25225}, year = {2019}, date = {2019-01-18}, journal = {Journal of the International AIDS Society}, abstract = { Abstract Introduction Pre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users. Methods The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a “bridge” to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples’ sense of protection against HIV infection and raising the prospect of a return to “live sex” (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention. Clinical Trial Number NCT02775929 }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Introduction Pre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users. Methods The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a “bridge” to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples’ sense of protection against HIV infection and raising the prospect of a return to “live sex” (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention. Clinical Trial Number NCT02775929 |
JP, Kaboggoza; X, Wang; M, Neary; P, Ayuso; C, Sekaggya-Wiltshire; S, Nakalema; A, Owen; M, McClure; M, Lamorde; M, Boffito A Lower Dose of Efavirenz Can Be Coadministered With Rifampicin and Isoniazid in Tuberculosis Patients Journal Article Open Forum Diseases , 6 (2), 2019. @article{JP2019, title = {A Lower Dose of Efavirenz Can Be Coadministered With Rifampicin and Isoniazid in Tuberculosis Patients}, author = {Kaboggoza JP and Wang X and Neary M and Ayuso P and Sekaggya-Wiltshire C and Nakalema S and Owen A and McClure M and Lamorde M and Boffito M}, url = {https://watermark.silverchair.com/ofz035.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlswggJXBgkqhkiG9w0BBwagggJIMIICRAIBADCCAj0GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM171Jo1MZdLPK4-CiAgEQgIICDnyb9uh2Ai8sXCED4DmtumguYfSbH3lGLmWfhenE4LFrjRAUAElNllazUkTGuNSWlPyMP9PIJUHrJRSsfmjRO6W-zjpSwTw6-A86XEYHXacYWG-DGYhAPK6hDKgr4ejiPzuv6YYTyHW3JZHfkkWTCxBKg6RIxcXdwi0OjyZxtBX_Guz8bxdGvvrZW9AbVU3uS8EhIDNjlCDL1WxITvNPsY9HFS9WOLTzC6k8uPyo0ccz9yCenTxK0cXLsFlCjpCPxtWLb7NPwaglrk37EoA9JtiBYRKkhNbDqOU0VF2ZIxZSbAliUsm1HYQFhLksy2G81GUgqXOvAgheLOqJ8r_63bPsRggw2KmPTH1cO1GsS6wBHfXpd2PNgXyAV-3gPIS1DABxdc-ahCw9fdhv-Wu6v7DIW0kQ0GaM7ERCAY6W9a-pL_UY-l4QkoHYdanKm9ggyS_pB5m3a1VOjKRzxceyhtd2kv6UyAp1a7HegcNs_7_BHSomtR81kJP4LczkF6CIykhsMAg_CDUEg8rQXlq4SnOEncZDivM8GoOPF6YZsylmJcN78c2hg_aVJE8hz1jIPOvFTkmQszEOg2PIopqKPXf2onYDVBl3-w07HzuKcrLslEMtmkmLhMhmMtCUZoext_bmMbrM9vnjr-vOJWJWldzKKZMOJhME94eCG4OkG-6C25gFGX3moLC3m8cnJjA}, doi = {10.1093/ofid/ofz035}, year = {2019}, date = {2019-01-16}, journal = {Open Forum Diseases }, volume = {6}, number = {2}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
AK, Musubire; DB, Meya; ET, Katabira; ACL, Meyer; PR, Bohjanen; DR, Boulware; F, Minja Epidemiology of non-traumatic spinal cord injury in Uganda: a single center, prospective study with MRI evaluation Journal Article BMC Neaurology , 19 (1), 2019. @article{AK2019, title = {Epidemiology of non-traumatic spinal cord injury in Uganda: a single center, prospective study with MRI evaluation}, author = {Musubire AK and Meya DB and Katabira ET and Meyer ACL and Bohjanen PR and Boulware DR and Minja F}, doi = {10.1186/s12883-019-1236-3}, year = {2019}, date = {2019-01-15}, journal = {BMC Neaurology }, volume = {19}, number = {1}, abstract = {Background A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda. Methods We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013–2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics. Results In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% (n = 72). Severe disease was present in 82% (n = 85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% (n = 44) of participants, with the highest mortality among those with extradural lesions (60%). Conclusion The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda. Methods We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013–2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics. Results In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% (n = 72). Severe disease was present in 82% (n = 85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% (n = 44) of participants, with the highest mortality among those with extradural lesions (60%). Conclusion The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis. |
DS, Lawrence; N, Youssouf; SF, Molloy; A, Alanio; M, Alufandika; DR, Boulware; T, Boyer-Chammard; T, Chen; F, Dromer; A, Hlupeni; W, Hope; MC, Hosseinipour; C, Kanyama; O, Lortholary; A, Loyse; DB, Meya; M, Mosepele; C, Muzoora; HC, Mwandumba; CE, Ndhlovu; L, Niessen; C, Schutz; KE, Stott; D, Wang; DG, Lalloo; G, Meintjes; S, Jaffar; TS, Harrison; JN, Jarvis Trails, 20 (1), 2019. @article{DS2019, title = {Correction to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial. }, author = {Lawrence DS and Youssouf N and Molloy SF and Alanio A and Alufandika M and Boulware DR and Boyer-Chammard T and Chen T and Dromer F and Hlupeni A and Hope W and Hosseinipour MC and Kanyama C and Lortholary O and Loyse A and Meya DB and Mosepele M and Muzoora C and Mwandumba HC and Ndhlovu CE and Niessen L and Schutz C and Stott KE and Wang D and Lalloo DG and Meintjes G and Jaffar S and Harrison TS and Jarvis JN}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332521/}, doi = {10.1186/s13063-018-3155-9}, year = {2019}, date = {2019-01-14}, journal = {Trails}, volume = {20}, number = {1}, abstract = {Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected. |
DS, Lawrence; N, Youssouf; SF, Molloy; A, Alanio; M, Alufandika; DR, Boulware; T, Boyer-Chammard; T, Chen; F, Dromer; A, Hlupeni; W, Hope; MC, Hosseinipour; C, Kanyama; O, Lortholary; A, Loyse; DB, Meya; M, Mosepele; C, Muzoora; HC, Mwandumba; CE, Ndhlovu; L, Niessen; C, Schutz; KE, Stott; D, Wang; DG, Lalloo; G, Meintjes; S, Jaffar; TS, Harrison; JN., Jarvis BMC, 20 (1), pp. 48, 2019. @article{DS2019b, title = {Correction: AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: Study protocol for a phase 3 randomised controlled non-inferiority trial }, author = {Lawrence DS and Youssouf N and Molloy SF and Alanio A and Alufandika M and Boulware DR and Boyer-Chammard T and Chen T and Dromer F and Hlupeni A and Hope W and Hosseinipour MC and Kanyama C and Lortholary O and Loyse A and Meya DB and Mosepele M and Muzoora C and Mwandumba HC and Ndhlovu CE and Niessen L and Schutz C and Stott KE and Wang D and Lalloo DG and Meintjes G and Jaffar S and Harrison TS and Jarvis JN.}, url = {https://experts.umn.edu/en/publications/correction-ambisome-therapy-induction-optimisation-ambition-high-}, doi = {DOI: 10.1186/s13063-018-3026-4)}, year = {2019}, date = {2019-01-14}, journal = {BMC}, volume = {20}, number = {1}, pages = {48}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
R, Rajasingham; DB, Meya; GS, Greene; A, Jordan; M, Nakawuka; TM, Chiller; DR, Boulware; BA., Larson Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis Journal Article PLOS ONE, pp. e0210105, 2019. @article{R2019h, title = {Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis}, author = {Rajasingham R and Meya DB and Greene GS and Jordan A and Nakawuka M and Chiller TM and Boulware DR and Larson BA. }, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210105}, doi = { https://doi.org/10.1371/journal.pone.0210105}, year = {2019}, date = {2019-01-10}, journal = {PLOS ONE}, pages = {e0210105}, abstract = {Abstract Background Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. Methods We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. Results In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. Conclusion CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective. Citation: Rajasingham R, Meya DB, Greene GS, Jordan A, Nakawuka M, Chiller TM, et al. (2019) Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis. PLoS ONE 14(1): e0210105. https://doi.org/10.1371/journal.pone.0210105 Editor: Eileen Stillwaggon, Gettysburg College, UNITED STATES Received: November 27, 2018; Accepted: December 16, 2018; Published: January 10, 2019 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: RR is supported by the National Institute of Allergy and Infectious diseases (K23AI138851). BL is supported by the CDC foundation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: BL was paid by the CDC foundation for this work. GG, AJ, and TC are employed by the CDC, which is a separate, independent entity from the CDC foundation The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. Methods We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. Results In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. Conclusion CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective. Citation: Rajasingham R, Meya DB, Greene GS, Jordan A, Nakawuka M, Chiller TM, et al. (2019) Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis. PLoS ONE 14(1): e0210105. https://doi.org/10.1371/journal.pone.0210105 Editor: Eileen Stillwaggon, Gettysburg College, UNITED STATES Received: November 27, 2018; Accepted: December 16, 2018; Published: January 10, 2019 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: RR is supported by the National Institute of Allergy and Infectious diseases (K23AI138851). BL is supported by the CDC foundation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: BL was paid by the CDC foundation for this work. GG, AJ, and TC are employed by the CDC, which is a separate, independent entity from the CDC foundation The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials. |
R, Parkes-Ratanshi; R, Kikonyogo; YH, Hsieh; E, Nakku-Joloba; YC, Manabe; CA, Gaydos; A, Rompalo Point-of-care diagnostics: needs of African health care workers and their role combating global antimicrobial resistance Journal Article International Journal of STD & AIDS, 30 (4), pp. 404-410, 2019. @article{R2019c, title = {Point-of-care diagnostics: needs of African health care workers and their role combating global antimicrobial resistance}, author = {Parkes-Ratanshi R and Kikonyogo R and Hsieh YH and Nakku-Joloba E and Manabe YC and Gaydos CA and Rompalo A}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693631/}, doi = {10.1177/0956462418807112}, year = {2019}, date = {2019-01-09}, journal = {International Journal of STD & AIDS}, volume = {30}, number = {4}, pages = {404-410}, abstract = {Point-of-care tests (POCTs) offer the opportunity for increased diagnostic capacity in resource-limited settings, where there is lack of electricity, technical capacity, reagents, and infrastructure. Understanding how POCTs are currently used and determining what health care workers (HCWs) need is key to development of appropriate tests. In 2016, we undertook an email survey of 7584 HCWs who had received training at the Infectious Diseases Institute, Uganda, in a wide variety of courses. HCWs were contacted up to three times and asked to complete the survey using Qualtrics software. Of 555 participants answering the survey (7.3% response rate), 62% completed. Ninety-one percent were from Uganda and 50.3% were male. The most commonly-used POCTs were pregnancy tests (74%), urine dipstick (71%), syphilis rapid test (66%), and Gram stain (41%). The majority (74%) practiced syndromic diagnosis for sexually transmitted infections/HIV. Lack of availability of POCTs, increased patient wait time, and lack of training were the leading barriers for POCT use. Increasing POCT availability and training could improve uptake of POCTs for sexually transmitted infections in Africa and decrease syndromic management. This could reduce overtreatment and slow the emergence of antibiotic resistance. This is the first published email survey of HCWs in Uganda; mechanisms to increase the response rate should be evaluated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Point-of-care tests (POCTs) offer the opportunity for increased diagnostic capacity in resource-limited settings, where there is lack of electricity, technical capacity, reagents, and infrastructure. Understanding how POCTs are currently used and determining what health care workers (HCWs) need is key to development of appropriate tests. In 2016, we undertook an email survey of 7584 HCWs who had received training at the Infectious Diseases Institute, Uganda, in a wide variety of courses. HCWs were contacted up to three times and asked to complete the survey using Qualtrics software. Of 555 participants answering the survey (7.3% response rate), 62% completed. Ninety-one percent were from Uganda and 50.3% were male. The most commonly-used POCTs were pregnancy tests (74%), urine dipstick (71%), syphilis rapid test (66%), and Gram stain (41%). The majority (74%) practiced syndromic diagnosis for sexually transmitted infections/HIV. Lack of availability of POCTs, increased patient wait time, and lack of training were the leading barriers for POCT use. Increasing POCT availability and training could improve uptake of POCTs for sexually transmitted infections in Africa and decrease syndromic management. This could reduce overtreatment and slow the emergence of antibiotic resistance. This is the first published email survey of HCWs in Uganda; mechanisms to increase the response rate should be evaluated. |
RR, Atherton; J, Ellis; FV, Cresswell; J, Rhein; DR., Boulware Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort Journal Article Wellcome Open Research, 3 (20), pp. eCollection 2018. , 2019. @article{RR2019b, title = {Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort}, author = {Atherton RR and Ellis J and Cresswell FV and Rhein J and Boulware DR. }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178913/}, doi = {doi: 10.12688/wellcomeopenres.14666.2}, year = {2019}, date = {2019-01-01}, journal = {Wellcome Open Research}, volume = {3}, number = {20}, pages = {eCollection 2018. }, abstract = {Abstract Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period. A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management. Keywords: Cryptococcus, cryptococcal meningitis, HIV, visual, ocular, ophthalmic}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period. A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management. Keywords: Cryptococcus, cryptococcal meningitis, HIV, visual, ocular, ophthalmic |
2018 |
Muhumuza, Simon; Akello, Evelyn; Kyomugisha-Nuwagaba, Charity; Baryamutuma, Rose; Sebuliba, Isaac; Lutalo, Ibrahim M; Kansiime, Edgar; Kisaakye, Linda N; Kiragga, Agnes N; King, Rachel; Bazeyo, William; Lindan, Christina Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study Journal Article PloS One, 12 (12), 2018. @article{Muhumuza2018, title = {Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study}, author = {Simon Muhumuza and Evelyn Akello and Charity Kyomugisha-Nuwagaba and Rose Baryamutuma and Isaac Sebuliba and Ibrahim M. Lutalo and Edgar Kansiime and Linda N. Kisaakye and Agnes N. Kiragga and Rachel King and William Bazeyo and Christina Lindan }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Retention-in-care-among-HIV-infected-pregnant-and-breastfeeding-women-on-lifelong-antiretroviral-therapy-in-Uganda-A-retrospective-cohort-study.pdf}, doi = { 10.1371/journal.pone.0187605}, year = {2018}, date = {2018-12-22}, journal = {PloS One}, volume = {12}, number = {12}, abstract = {BACKGROUND: In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program. METHODS: We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables. RESULTS: The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002). CONCLUSION: Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program. METHODS: We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables. RESULTS: The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002). CONCLUSION: Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority. |
RR, Atherton; J, Ellis; FV, Cresswell; J, Rhein; DR, Boulware Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort. Journal Article Welcome Open Access , 3 (80), 2018. @article{RR2018, title = {Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort. }, author = {Atherton RR and Ellis J and Cresswell FV and Rhein J and Boulware DR}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178913/}, doi = {10.12688/wellcomeopenres.14666.2}, year = {2018}, date = {2018-10-12}, journal = {Welcome Open Access }, volume = {3}, number = {80}, abstract = {Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period. A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period. A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management. |
Bahr, Nathan C; Nuwagira, Edwin; Evans, Emily E; Cresswell, Fiona V; Bystrom, Philip V; Byamukama, Adolf; Bridge, Sarah C; Bangdiwala, Ananta S; Meya, David B; Denkinger, Claudia M; Muzoora, Conrad; Boulware, David R Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Journal Article Lancent Infectious Diseases, 18 (1), pp. 68-75, 2018. @article{Bahr2018, title = {Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.}, author = {Nathan C Bahr and Edwin Nuwagira and Emily E Evans and Fiona V Cresswell and Philip V Bystrom and Adolf Byamukama and Sarah C Bridge and Ananta S Bangdiwala and David B Meya and Claudia M Denkinger and Conrad Muzoora and David R Boulware }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Diagnostic-accuracy-of-Xpert-MTBRIF-Ultra-for-tuberculous-meningitis-in-HIV-infected-adults-a-prospective-cohort-study..pdf}, doi = {: 10.1016/S1473-3099(17)30474-7}, year = {2018}, date = {2018-09-14}, journal = {Lancent Infectious Diseases}, volume = {18}, number = {1}, pages = {68-75}, abstract = {BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation. |
Freemen, Esther E; Semeere, Aggrey; Osman, Hany; Peterso, Gary; and Milind Rajadhyaksha, Salvador Gonzalez; Martin, Jeffrey N; Anderson, Rox R; Tearney, Guillermo J; Kang, Dongkyun Smartphone Confocal Microscopy for Imaging Cellular Structures In Human Skin in Vivo. Journal Article BIOMEDICAL OPTICS EXPRESS , 9 (4), pp. 1906–1915, 2018. @article{Freemen2018, title = {Smartphone Confocal Microscopy for Imaging Cellular Structures In Human Skin in Vivo. }, author = {Esther E Freemen and Aggrey Semeere and Hany Osman and Gary Peterso and Milind Rajadhyaksha,and Salvador Gonzalez and Jeffrey N Martin and R. Rox Anderson and Guillermo J Tearney and Dongkyun Kang}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Smartphone-Confocal-Microscopy-for-Imaging-Cellular-Structures-In-Human-Skin-in-Vivo.-4.pdf}, doi = {10.1364/BOE.9.001906}, year = {2018}, date = {2018-04-20}, journal = { BIOMEDICAL OPTICS EXPRESS }, volume = {9}, number = {4}, pages = {1906–1915}, abstract = { We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement OCIS codes: (170.1790) Confocal microscopy; (170.1870) Dermatology. }, keywords = {}, pubstate = {published}, tppubtype = {article} } We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement OCIS codes: (170.1790) Confocal microscopy; (170.1870) Dermatology. |
Nyakato, Patience; Kiragga, Agnes N; Kambugu, Andrew; Bradley, John; Baisley, Kathy BMJ Open, 8 (4), 2018. @article{Nyakato2018, title = {Correction of estimates of retention in care among a cohort of HIV-positive patients in Uganda in the period before starting ART: a sampling-based approach}, author = {Patience Nyakato and Agnes N Kiragga and Andrew Kambugu and John Bradley and Kathy Baisley}, url = {https://bmjopen.bmj.com/content/8/4/e017487.long}, year = {2018}, date = {2018-04-20}, journal = {BMJ Open}, volume = {8}, number = {4}, abstract = {OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. |
Cresswell, Fiona V; Bangdiwala, Ananta S; Meya, David B; Bahr, Nathan C; Vidal, Jose E; M. Estée Török, Le Thi Phuong ; Thwaites, Thao Guy E; Boulwar, David R Absence of Cerebrospinal Fluid Pleocytosis in Tuberculous Meningitis is a Common Occurrence in HIV Co-infection and a Predictor of Poor Outcomes Journal Article International Jouranl of Infectious Deseases, 67 , pp. 77-78, 2018. @article{Cresswell2018, title = {Absence of Cerebrospinal Fluid Pleocytosis in Tuberculous Meningitis is a Common Occurrence in HIV Co-infection and a Predictor of Poor Outcomes }, author = {Fiona V Cresswell and Ananta S Bangdiwala and David B Meya and Nathan C Bahr and Jose E Vidal and M. Estée Török, Le Thi Phuong and Thao Guy E Thwaites and David R Boulwar}, url = {https://www.ijidonline.com/article/S1201-9712(18)30015-8/fulltext}, doi = {10.1016/j.ijid.2018.01.014.}, year = {2018}, date = {2018-03-01}, journal = {International Jouranl of Infectious Deseases}, volume = {67}, pages = {77-78}, abstract = {We read with interest the article by Erdem et al. reporting absence of cerebrospinal fluid (CSF) pleocytosis (≤5 cells/l) in 3% (19/507) of HIV-negative tuberculous meningitis (TBM) patients (Erdem et al., 2017). We wish to highlight both the significance and higher incidence of acellular CSF among HIV-infected adults with TBM. In reviewing 85 microbiologically-confirmed, HIV-associated TBM cases in Uganda, 33% (28/85) had acellular CSF. Acellular CSF was also commonly reported among other HIV-infected microbiologically-confirmed TBM cohorts: 26% (5/19) in Zimbabwe, 19% (20/108) in Brazil, and 21% (18/91) in Argentina (Table1)(Cecchini et al., 2007, Croda et al., 2010, Hakim et al., 2000, Vidal et al., 2010). Prevalence of acellular CSF correlated with the severity of immunosuppression in the Argentinian cohort and occurred twice as often in CD4 counts <50 cells/l(33%, 9/28) than with >50 cells/ (15%, 5/31) (Cecchini et al., 2009). In Vietnam, acellular CSF is less common (4%, 20/461) despite advanced immunosuppression (median CD4 39 cells). Variation between cohorts may be attributable to variable time to CSF analysis, M. tuberculosis strain type, or genetic differences in host immune responses between geographically distinct cohorts (Caws et al., 2008). }, keywords = {}, pubstate = {published}, tppubtype = {article} } We read with interest the article by Erdem et al. reporting absence of cerebrospinal fluid (CSF) pleocytosis (≤5 cells/l) in 3% (19/507) of HIV-negative tuberculous meningitis (TBM) patients (Erdem et al., 2017). We wish to highlight both the significance and higher incidence of acellular CSF among HIV-infected adults with TBM. In reviewing 85 microbiologically-confirmed, HIV-associated TBM cases in Uganda, 33% (28/85) had acellular CSF. Acellular CSF was also commonly reported among other HIV-infected microbiologically-confirmed TBM cohorts: 26% (5/19) in Zimbabwe, 19% (20/108) in Brazil, and 21% (18/91) in Argentina (Table1)(Cecchini et al., 2007, Croda et al., 2010, Hakim et al., 2000, Vidal et al., 2010). Prevalence of acellular CSF correlated with the severity of immunosuppression in the Argentinian cohort and occurred twice as often in CD4 counts <50 cells/l(33%, 9/28) than with >50 cells/ (15%, 5/31) (Cecchini et al., 2009). In Vietnam, acellular CSF is less common (4%, 20/461) despite advanced immunosuppression (median CD4 39 cells). Variation between cohorts may be attributable to variable time to CSF analysis, M. tuberculosis strain type, or genetic differences in host immune responses between geographically distinct cohorts (Caws et al., 2008). |
Castelnuovo, Barbara; Mubiru, Frank; Kiragga, Agnes N; Musomba, Rachel; Mbabazi, Olive; Gonza, Paul; Kambugu, Andrew; Ratanshi, Rosalind Parks Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda Journal Article BMJ Open, 8 (2), 2018. @article{Castelnuovo2018, title = {Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda}, author = {Barbara Castelnuovo and Frank Mubiru and Agnes N Kiragga and Rachel Musomba and Olive Mbabazi and Paul Gonza and Andrew Kambugu and Rosalind Parks Ratanshi}, url = {https://bmjopen.bmj.com/content/8/2/e015490.long}, year = {2018}, date = {2018-02-21}, journal = {BMJ Open}, volume = {8}, number = {2}, abstract = {Purpose Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. Participants A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. Findings to date Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. Future plans Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug–drug interactions between ART and common drugs used for non-communicable diseases. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Purpose Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. Participants A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. Findings to date Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. Future plans Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug–drug interactions between ART and common drugs used for non-communicable diseases. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
Nakiyingi, Lydia; Nakanwagi, Prossy; Briggs, Jessica; Agaba, Tifu; Mubiru, Frank; Mugenyi, Mark; Ssengooba, Willy; Joloba, Moses L; Manabe, Yukari C BMC Infectious Diseases , 18 (1), pp. 87, 2018. @article{Nakiyingi2018, title = {Performance of loop-mediated isothermal amplification assay in the diagnosis of pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda}, author = {Lydia Nakiyingi and Prossy Nakanwagi and Jessica Briggs and Tifu Agaba and Frank Mubiru and Mark Mugenyi and Willy Ssengooba and Moses L. Joloba and Yukari C. Manabe}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Performance-of-loop-mediated-isothermal-amplification-assay-in-the-diagnosis-of-pulmonary-tuberculosis-in-a-high-prevalence-TB-or-HIV-rural-setting-in-Uganda.pdf}, doi = { 10.1186/s12879-018-2992-1}, year = {2018}, date = {2018-02-21}, journal = { BMC Infectious Diseases }, volume = {18}, number = {1}, pages = {87}, abstract = {BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise. |
Barbara Castelnuovo Frank Mubiru, Shadia Nakalema Adelline Twimukye ; Kiragga, Agnes Describing the retention in care of human immunodeficiency viruspositive young adults who transition from adolescent to adult care Journal Article International Health, 10 (4), pp. 318-320, 2018. @article{Castelnuovo2018b, title = {Describing the retention in care of human immunodeficiency viruspositive young adults who transition from adolescent to adult care}, author = {Barbara Castelnuovo, Frank Mubiru, Shadia Nakalema, Adelline Twimukye and Agnes Kiragga }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Describing-the-retention-in-care-of-human-immunodeficiency-virus-positive-young-adults-who-transition-from-adolescent-to-adult-care.pdf}, doi = {10.1093/inthealth/ihx063.}, year = {2018}, date = {2018-02-01}, journal = {International Health}, volume = {10}, number = {4}, pages = {318-320}, abstract = {Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group |
IeDEA, COHERE Cohort Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Program Journal Article Clinical Infectious Diseases, 66 (6), pp. 893–903, 2018. @article{IeDEA2018, title = {Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Program}, author = {IeDEA, COHERE Cohort }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Global-Trends-in-CD4-Cell-Count-at-the-Start-of-Antiretroviral-Therapy-Collaborative-Study-of-Treatment-Program.pdf}, doi = {10.1093/cid/cix915}, year = {2018}, date = {2018-01-25}, journal = {Clinical Infectious Diseases}, volume = {66}, number = {6}, pages = { 893–903}, abstract = {Background Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. Results A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. Results A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART. |
