@article{Seremba2017,

title = {Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda},

author = {E Seremba and V Ssempijja and S Kalibbala and RH Gray and MJ Wawer and F Nalugoda and C Casper and W Phipps P Ocama and D Serwadda and DL Thomas and SJ Reynold},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Hepatitis-B-incidence-and-prevention-with-antiretroviral-therapy-among-HIV-positive-individuals-in-Uganda.pdf},

doi = {10.1097/QAD.0000000000001399},

year  = {2017},

date = {2017-03-27},

journal = {AIDS},

volume = {31},

number = {6},

pages = {781-786},

abstract = {OBJECTIVE:



Antiretroviral therapy (ART) may interfere with replication of hepatitis B virus (HBV), raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.

METHODS:



We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-hepatitis B core-negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals (CIs), whereas Cox proportional regression methods were used to estimate hazard ratios (HRs).

RESULTS:



Thirty-nine HBV infections occurred over 3342 person-years, incidence 1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.49/100 person-years with ART and 2.3/100 person-years without ART [adjusted HR (aHR) 0.25, 95% CI 0.1-0.5, P < 0.001], and with lamivudine (3TC) use: 0.58/100 person-years) with 3TC and 2.25/100 person-years without 3TC (aHR 0.32, 95% CI 0.1-0.7, P =  < 0.007). No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: 0.6/100 person-years with 400 copies/ml or less and 4.0/100 person-years with more than 400 copies/ml (aHR, 6.4, 95% CI 2.2-19.0, P < 0.001); and with age: 15-29 years versus 40-50 years (aHR 3.2, 95% CI 1.2-9.0); 30-39 years versus 40-50 years (aHR 2.1, 95% CI 0.9-5.3).

CONCLUSION:



HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Anna Bershetyn2017,

title = {The Causal Effect of Tracing by Peer Health Workers on Return to Clinic Among Patients Who Were Lost to Follow-up From Antiretroviral Therapy in Eastern Africa: A “Natural Experiment” Arising From Surveillance of Lost Patients},

author = {Anna Bershetyn and Thomas A. Odeny and Rita Lyamuya and Alice Nakiwogga-Muwanga and Lameck Diero and Mwebesa Bwana and Paula Braitstein and Geoffrey Somi and Andrew Kambugu and Elizabeth Bukusi and Wendy Hartogensis and David V. Glidden and Kara Wools-Kaloustian and Constantin Yiannoutsos and Jeffrey Martin and and Elvin H. Geng; for the East Africa International Epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-Causal-Effect-of-Tracing-by-Peer-Health-Workers-on-Return-to-Clinic-Among-Patients-Who-Were-Lost-to-Follow-up-From-Antiretroviral-Therapy-in-Eastern-Africa-A-“Natural-Experiment”-Arisi.pdf},

doi = {10.1093/cid/cix191},

year  = {2017},

date = {2017-03-17},

journal = {Clinical Infectious Diseases},

volume = {64},

number = {11},

pages = {1547–1554},

abstract = {Background. The effect of tracing human immunodeficiency virus (HIV)–infected patients who are lost to follow-up (LTFU) on reengagement has not been rigorously assessed. We carried out an ex post analysis of a surveillance study in which LTFU patients were randomly selected for tracing to identify the effect of tracing on reengagement. Methods. We evaluated HIV-infected adults on antiretroviral therapy who were LTFU (>90 days late for last visit) at 14 clinics in Uganda, Kenya, and Tanzania. A random sample of LTFU patients was selected for tracing by peer health workers. We assessed the effect of selection for tracing using Kaplan-Meier estimates of reengagement among all patients as well as the subset of LTFU patients who were alive, contacted in person by the tracer, and out of care. Results. Of 5781 eligible patients, 991 (17%) were randomly selected for tracing. One year after selection for tracing, 13.3% (95% confidence interval [CI], 11.1%–15.3%) of those selected for tracing returned compared with 10.0% (95% CI, 9.1%–10.8%) of those not randomly selected, an adjusted risk difference of 3.0% (95% CI, .7%–5.3%). Among patients found to be alive, personally contacted, and out of care, tracing increased the absolute probability of return at 1 year by 22% (95% CI, 7.1%–36.2%). The effect of tracing on rate of return to clinic decayed with a half-life of 7.0 days after tracing (95% CI, 2.6 %–12.9%). Conclusions. Tracing interventions increase reengagement, but developing methods for targeting LTFU patients most likely to benefit can make this practice more efficient. Keywords. antiretroviral therapy; Africa; retention; loss to follow-up.

 },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lofgren2017,

title = {Differences in Immunologic Factors Among Patients Presenting with Altered Mental Status During Cryptococcal Meningitis},

author = {Sarah Lofgren and Kathy H. Hullsiek and Bozena M. Morawski and Henry W. Nabeta and Reuben Kiggundu and Kabanda Taseera and Abdu Musubire and Charlotte Schutz and Mahsa Abassi and Nathan C. Bahr and Lillian Tugume and Conrad Muzoora and Darlisha A. Williams and Melissa A. Rolfes and Sruti S. Velamakanni and Radha Rajasingham and Graeme Meintjes and Joshua Rhein and David B. Meya and David R. Boulware on behalf of the COAT and ASTRO-CM Trial Teams },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Differences-in-Immunologic-Factors-Among-Patients-Presenting-with-Altered-Mental-Status-During-Cryptococcal-Meningitis.pdf},

doi = {10.1093/infdis/jix033},

year  = {2017},

date = {2017-03-01},

journal = {Journal of infectious Diseases},

volume = {215},

number = {5},

pages = {693-697},

abstract = {Altered mental status in cryptococcal meningitis results in poorer survival, but underlying causes of altered mentation are poorly understood. Within two clinical trials, we assessed risk factors for altered mental status (GCS score<15) considering baseline clinical characteristics, CSF cytokines/chemokines, and antiretroviral therapy. Among 326 enrolled participants, 97 (30%) had GCS<15 and these patients had lower median CSF cryptococcal antigen titers (P = .042) and CCL2 (P = .005) but higher opening pressures (320 vs. 269 mm H2O; P = .016), IL-10 (P = .044), and CCL3 (P = .008) compared with persons with GCS=15. Altered mental status may be associated with host immune response rather than Cryptococcus burden.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orikiiriza2017,

title = {Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria},

author = {Judy Orikiiriza and Izabella Surowiec and Elisabeth Lindquist and Mari Bonde and Jimmy Magambo and Charles Muhinda and Sven Bergström and Johan Trygg and Johan Normark },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Lipid-response-patterns-in-acute-phase-paediatric-Plasmodium-falciparum-malaria.pdf},

doi = {10.1007/s11306-017-1174-2},

year  = {2017},

date = {2017-02-23},

journal = {Metabolomics},

volume = {13},

number = {4},

abstract = {INTRODUCTION:



Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.

METHODS:



Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5-6 years. Lipids from patient's plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.

RESULTS:



We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.

CONCLUSIONS:



This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.

KEYWORDS:



Lipidomics profiling; Lysophosphatidylcholines; Malaria; Plasmodium falciparum; Triacylglycerides},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lofgren2017b,

title = {Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings},

author = {Sarah Lofgren, Mahsa Abassi, Joshua Rhein & David R Boulware},

doi = {https://doi.org/10.1080/14787210.2017.1285697},

year  = {2017},

date = {2017-02-19},

journal = {Expert Review of Anti-infective Therapy },

volume = {15},

number = {4},

pages = {331-340},

abstract = {Introduction: 

Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths.



Areas covered: 

Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent.



Expert commentary: 

Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.



KEYWORDS: HIVAIDScryptococcal meningitisCM-IRISimmune reconstitution inflammatory syndromereviewantiretroviral therapyantifungal therapysertraline},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Neary2017,

title = {The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine},

author = {M Neary, M Lamorde, A Olagunju, KM Darin, C Merry, P Byakika-Kibwika, DJ Back, M Siccardi, A Owen, KK Scarsi},

doi = {https://doi.org/10.1002/cpt.667},

year  = {2017},

date = {2017-02-10},

journal = {Clinical Pharmacology & Therapeutics},

volume = {102},

number = {3},

pages = {529-536},

abstract = {Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based antiretroviral therapy (ART), in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin. Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Abongomera2017,

title = {Improved Adherence to Antiretroviral Therapy Observed Among HIV-Infected Children Whose Caregivers had Positive Beliefs in Medicine in Sub-Saharan Africa},

author = {G. Abongomera and A. Cook and V. Musiime and C. Chabala and M. Lamorde and J. Abach and M. Thomason and V. Mulenga and A. Kekitiinwa and R. Colebunders and C. Kityo and A. S. Walker and D. M. Gibb},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Improved-Adherence-to-Antiretroviral-Therapy-Observed-Among-HIV-Infected-Children-Whose-Caregivers-had-Positive-Beliefs-in-Medicine-in-Sub-Saharan-Africa.pdf},

doi = {10.1007/s10461-016-1582-8},

year  = {2017},

date = {2017-02-07},

journal = {AIDS and Behavior},

volume = {21},

number = {2},

pages = {441-449},

abstract = { A high level of adherence to antiretroviral treatment is essential for optimal clinical outcomes in HIV infection, but measuring adherence is difficult. We investigated whether responses to a questionnaire eliciting caregiver beliefs in medicines were associated with adherence of their child (median age 2.8 years), and whether this in turn was associated with viral suppression. We used the validated beliefs in medicine questionnaire (BMQ) to measure caregiver beliefs, and medication event monitoring system caps to measure adherence. We found significant associations between BMQ scores and adherence, and between adherence and viral suppression. Among children initiating Antiretroviral therapy (ART), we also found significant associations between BMQ ‘necessity’

scores, and BMQ ‘necessity-concerns’ scores, and later viral suppression. This suggests that the BMQ may be a valuable tool when used alongside other adherence measures, and that it remains important to keep caregivers well informed about the long-term necessity of their child’s ART.

Keywords Adherence  Children  Beliefs in medicine  Sub-Saharan Africa  Antiretroviral therapy

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lund2017,

title = {Correction for Lund et al., HIV-1- Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis},

author = {Jennifer M. Lund, Kristina Broliden, Maria N. Pyra, Katherine K. Thomas, Deborah Donnell, Elizabeth Irungu, Timothy R. Muwonge, Nelly Mugo, Madhuri Manohar, Marianne Jansson, Romel Mackelprang, Mark A. Marzinke, Jared M. Baeten, Jairam R. Lingappa, for the Partners PrEP Study},

year  = {2017},

date = {2017-02-01},

journal = {American Society for Microbiology. },

volume = {91},

number = {3},

pages = {e02074-16 },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Morawski2017b,

title = {Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis},

author = {Tugume Morawski and Abassi and Bahr Kiggundu and Nabeta Hullsiek and Taseera Musubire and Schutz Muzoora and Williams Rolfes and Meintjes Rhein and Meya Boulware },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Prognostic-Implications-of-Baseline-Anemia-and-Changes-in-Hemoglobin-Concentrations-with-Amphotericin-B-therapy-for-Cryptococcal-Meningitis.pdf},

doi = {10.1111/hiv.12387},

year  = {2017},

date = {2017-01-28},

journal = {HHS Public Access},

volume = {18},

number = {1},

pages = {13-20},

abstract = {OBJECTIVES:



Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival.

METHODS:



We used data from Ugandan and South African trial participants to characterize the variation of haemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Anaemia severity was classified based on the haemoglobin concentration at cryptococcal meningitis diagnosis, and nadir haemoglobin values during amphotericin induction. Cox proportional hazard models were used to estimate 2- and 10-week mortality risk. We also estimated 10-week mortality risk among participants with nadir haemoglobin < 8.5 g/dL during amphotericin induction and who survived ≥ 2 weeks post-enrolment.

RESULTS:



The median haemoglobin concentration at meningitis diagnosis was 11.5 g/dL [interquartile range (IQR) 9.7-13 g/dL; n = 311] with a mean decline of 4.2 g/dL [95% confidence interval (CI) -4.6 to -3.8; P < 0.001; n = 148] from diagnosis to nadir value among participants with baseline haemoglobin ≥ 8.5 g/dL. The median haemoglobin concentration was 8.1 g/dL (IQR 6.5-9.5 g/dL) at 2 weeks, increasing to 9.4 g/dL (IQR 8.2-10.9 g/dL) by 4 weeks and continuing to increase to 12 weeks. Among participants with haemoglobin < 8.5 g/dL at diagnosis, mortality risk was elevated at 2 weeks [hazard ratio (HR) 2.7; 95% CI 1.5-4.9; P < 0.01] and 10 weeks (HR 1.8; 95% CI 1.1-2.2; P = 0.03), relative to those with haemoglobin ≥ 8.5 g/dL. New-onset anaemia occurring with amphotericin therapy did not have a statistically significant association with 10-week mortality (HR 2.0; 95% CI 0.5-9.1; P = 0.4).

CONCLUSIONS:



Amphotericin induced significant haemoglobin declines, which were mostly transient and did not impact 10-week mortality. Individuals with moderate to life-threatening anaemia at baseline had a higher mortality risk at 2 and 10 weeks post-enrolment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wanyama2017b,

title = {Significant rates of risky sexual behaviours among HIV-infected patients failing first-line ART: A sub-study of the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial},

author = {Jane N Wanyama and Maria S Nabaggala and Bonnie Wandera and Agnes N Kiragga and Barbara Castelnuovo and Ivan K Mambule and Josephine Nakajubi and Andrew D Kambugu and Nicholas I Paton and Rhoda K Wanyenze and Robert Colebunders and Philippa Easterbrook},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Significant-rates-of-risky-sexual-behaviours-among-HIV-infected-patients-failing-first-line-ART-A-sub-study-of-the-Europe–Africa-Research-Network-for-the-Evaluation-of-Second-line-Therapy.pdf},

doi = { 10.1177/0956462417724707},

year  = {2017},

date = {2017-01-17},

journal = {Internatio Journal for STDS & AIDS},

volume = {29},

number = {3},

pages = {287-297},

abstract = {There are limited data on the prevalence of risky sexual behaviours in individuals failing first-line antiretroviral therapy (ART) and changes in sexual behaviour after switch to second-line ART. We undertook a sexual behaviour sub-study of Ugandan adults enrolled in the Europe–Africa Research Network for the Evaluation of Second-line Therapy trial. A standardized questionnaire was used to collect sexual behaviour data and, in particular, risky sexual behaviours (defined as additional sexual partners to main sexual partner, inconsistent use of condoms, non-disclosure to sexual partners, and exchange of money for sex). Of the 79 participants enrolled in the sub-study, 62% were female, median age (IQR) was 37 (32–42) years, median CD4 cell count (IQR) was 79 (50–153) cells/µl, and median HIV viral load log was 4.9 copies/ml (IQR: 4.5–5.3) at enrolment. The majority were in long-term stable relationships; 69.6% had a main sexual partner and 87.3% of these had been sexually active in the preceding six months. At enrolment, around 20% reported other sexual partners, but this was higher among men than women (36% versus 6.7 %, p < 0.001). In 50% there was inconsistent condom use with their main sexual partner and a similar proportion with other sexual partners, both at baseline and follow-up. Forty-three per cent of participants had not disclosed their HIV status to their main sexual partner (73% with other sexual partners) at enrolment, which was similar in men and women. Overall, there was no significant change in these sexual behaviours over the 96 weeks following switch to second-line ART, but rate of non-disclosure of HIV status declined significantly (43.6% versus 19.6%, p <0.05). Among persons failing first-line ART, risky sexual behaviours were prevalent, which has implications for potential onward transmission of drug-resistant virus. There is need to intensify sexual risk reduction counselling and promotion of partner testing and disclosure, especially at diagnosis of treatment failure and following switch to second- or third-line ART.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mavoko2017,

title = {Efficacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of first-line recommended ACT (QUINACT): a bicentre, open-label, phase 3, randomised controlled trial. },

author = {Hypolite Muhindo Mavoko and Carolyn Nabasumba and Raquel Inocêncio da Luz and Halidou Tinto and Umberto D’Alessandro and Andrew Kambugu and Vito Baraka and Anna Rosanas-Urgell and Pascal Lutumba and Jean-Pierre Van geertruyden },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Efficacy-and-safety-of-re-treatment-with-the-same-artemisinin-based-combination-treatment-ACT-compared-with-an-alternative-ACT-and-quinine-plus-clindamycin-after-failure-of-first-line-re.pdf},

doi = {10.1016/S2214-109X(16)30236-4},

year  = {2017},

date = {2017-01-05},

journal = {Lancent Globol  Health},

volume = {5},

number = {1},

pages = {60-68},

abstract = {Background Quinine or alternative artemisinin-based combination treatment (ACT) is the recommended rescue treatment for uncomplicated malaria. However, patients are often re-treated with the same ACT though it is unclear whether this is the most suitable approach. We assessed the effi  cacy and safety of re-treating malaria patients with uncomplicated failures with the same ACT used for the primary episode, compared with other rescue treatments.

Methods This was a bicentre, open-label, randomised, three-arm phase 3 trial done in Lisungi health centre in DR Congo, and Kazo health centre in Uganda in 2012–14. Children aged 12–60 months with recurrent malaria infection after treatment with the fi rst-line ACT were randomly assigned to either re-treatment with the same fi rst-line ACT, an alternative ACT,  which were given for 3 days, or quinine-clindamycin (QnC), which was given for 5–7 days, following a 2:2:1 ratio. Randomisation was done by computer-generated randomisation list in a block design by country. The three treatment groups were assumed to have equivalent effi  cacy above 90%. Both the research team and parents or guardians were aware of treatment allocation. The primary outcome was the proportion of patients with an adequate clinical and parasitological response (ACPR) at day 28, in the per-protocol population. This trial was registered under the numbers NCT01374581 in ClinicalTrials.gov and PACTR201203000351114 in the Pan African Clinical Trials Registry.

Findings From May 22, 2012, to Jan 31, 2014, 571 children were included in the trial. 240 children were randomly assigned to the re-treatment ACT group, 233 to the alternative ACT group, and 98 to the QnC group. 500 children were assessed for the primary outcome. 71 others were not included because they did not complete the follow-up or PCR genotyping result was not conclusive. The ACPR response was similar in the three groups: 91·4% (95% CI 87·5–95·2) for the re-treatment ACT, 91·3% (95% CI 87·4–95·1) for the alternative ACT, and 89·5% (95% CI 83·0–96·0) for QnC. The estimates for rates of malaria recrudescence in the three treatment groups were similar (log-rank test: χ²=0·22, p=0·894). Artemether-lumefantrine was better tolerated than QnC (p=0·0005) and artesunateamodiaquine (p<0·0001) in the modifi ed intention-to-treat analysis. No serious adverse events were observed. The most common adverse events reported in the re-treatment ACT group were anorexia (31 [13%] of 240 patients), asthenia (20 [8%]), coughing (16 [7%]), abnormal behaviour (13 [5%]), and diarrhoea (12 [5%]). Anorexia (13 [6%] of 233 patients) was the most frequently reported adverse event in the alternative ACT group. The most commonly reported adverse events in the QnC group were anorexia (12 [12%] of 98 patients), abnormal behaviour (6 [6%]), asthenia (6 [6%]), and pruritus (5 [5%]).

Interpretation Re-treatment with the same ACT shows similar effi  cacy as recommended rescue treatments and could be considered for rescue treatment for Plasmodium falciparum malaria. However, the eff ect of this approach on the selection of resistant strains should be monitored to ensure that re-treatment with the same ACT does not contribute to P falciparum resistance.

Funding Fonds Wetenschappelijk Onderzoek, Vlaamse Interuniversitaire Raad-Universitaire Ontwikkelings Samenwerking, European and Developing Countries Clinical Trials Partnership, and the Belgian Technical Cooperation-Programme d’Etudes et d’Expertises-in the Democratic Republic of Congo.

Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vonBraun2017,

title = {Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis},

author = {Amrei von Braun and Christine Sekaggya‑Wiltshire and Alexandra U. Scherrer and Brian Magambo and Andrew Kambugu and Jan Fehr and Barbara Castelnuovo},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Early-virological-failure-and-HIV-drug-resistance-in-Ugandan-adults-co-infected-with-tuberculosis.pdf},

doi = { 10.1186/s12981-016-0128-5},

year  = {2017},

date = {2017-01-05},

journal = {AIDS Research and Therapy},

volume = {14},

number = {1},

abstract = {Purpose: This cross‑sectional study took place in the integrated tuberculosis (TB) clinic of a large outpatient clinic for HIV‑infected patients in Kampala, Uganda. The purpose of this study was to describe the proportion of TB/HIV co‑infected adults with virological failure, type and frequency of HIV drug resistance‑associated mutations, and the proportion of patients with suboptimal efavirenz levels. Methods: HIV‑1 plasma viral loads, CD4 cell count measurements, and efavirenz serum concentrations were done in TB/HIV co‑infected adults. Genotypic resistance testing was performed in case of confirmed virological failure. Results: After a median time on ART of 6 months, virological failure was found in 22/152 patients (14.5%). Of 147 participants with available efavirenz serum concentration, 26 (17.6%) had at least one value below the reference range, including 20/21 (95.2%) patients with confirmed virological failure. Genotypic resistance testing was available for 16/22 (72.7%) patients, of which 15 (93.8%) had at least one major mutation, most commonly M184V (81.2%) and K103NS (68.8%). Conclusion: We found a high proportion of TB/HIV co‑infected patients with virological failure, the majority of which had developed relevant resistance‑mutations after a median time on anti‑retroviral treatment (ART) of 6 months. Virological monitoring should be prioritized in TB/HIV co‑infected patients in resource‑limited settings. Keywords: Tuberculosis/HIV co‑infection, Treatment monitoring, Virological failure, HIV drug resistance, Efavirenz

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wanyama2017,

title = {Persons living with HIV infection on antiretroviral therapy also consulting traditional healers: a study in three African countries},

author = {Jane N Wanyama and Sharon Tsui and Cynthia Kwok and Rhoda K Wanyenze and Julie A Denison and Olivier Koole and Eric van Praag and Barbara Castelnuovo and Fred Wabwire-Mangen and Gideon P Kwesigabo and Robert Colebunders},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Persons-living-with-HIV-infection-on-antiretroviral-therapy-also-consulting-traditional-healers-a-study-in-three-African-countries.pdf},

doi = {10.1177/0956462416685890},

year  = {2017},

date = {2017-01-01},

journal = {Internatio Journal for STDS & AIDS},

volume = {28},

number = {10},

pages = {1018-1027},

abstract = {Traditional healers provide healthcare to a substantial proportion of people living with HIV infection (PLHIV) in high HIV burden countries in sub-Saharan Africa. However, the impact on the health of retained patients visiting traditional healers is unknown. In 2011, a study to asses adherence to anti-retroviral therapy (ART) performed in 18 purposefully selected HIV treatment centers in Tanzania, Zambia and Uganda showed that ‘consulting a traditional healer/herbalist because of HIV’ was an independent risk factor for incomplete ART adherence. To identify characteristics of PLHIV on ART who were also consulting traditional healers, we conducted a secondary analysis of the data from this study. It was found that 260 (5.8%) of the 4451 patients enrolled in the study had consulted a traditional healer during the last three months because of HIV. In multivariable analysis, patients with fewer HIV symptoms, those who had been on ART for >5.3 years and those from Tanzania were more likely to have consulted a traditional healer. However, at the time of the study, there was a famous healer in Manyara district, Loliondo village of Tanzania who claimed his herbal remedy was able to cure all chronic diseases including HIV. HIV treatment programs should be aware that patients with fewer HIV symptoms, those who have been on ART for five or more years, and patients attending ART centers near famous traditional healers are likely to consult traditional healers. Such patients may need more support or counseling about the risks of both stopping ARTand poor adherence. Considering the realities of inadequate human resources for health and the burden of disease caused by HIV in sub-Saharan Africa, facilitating a collaboration between allopathic and traditional health practitioners is recommended.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{C. Griffith2017,

title = {Premature Coronary Artery Disease and ST-Elevation Myocardial Infarction in a 24-Year-Old Man With Perinatally Acquired Human Immunodeficiency Virus: A Case Report},

author = {David C. Griffith and Konstantinos N. Aronis and Angela M. Orozco and Thomas A. Traill and Yukari C. Manabe and Allison L. Agwu},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Premature-Coronary-Artery-Disease-and-ST-Elevation-Myocardial-Infarction-in-a-24-Year-Old-Man-With-Perinatally-Acquired-Human-Immunodeficiency-Virus-A-Case-Report.pdf},

doi = {10.1093/ofid/ofw260},

year  = {2017},

date = {2017-01-01},

journal = {Open Forum Infectious Diseases},

volume = {14},

number = {1},

abstract = {Patients with human immunodeficiency virus (HIV) have increased risk of cardiovascular disease. Although evidence of subclinical atherosclerosis in perinatally acquired HIV (PHIV) is available, myocardial infarction has not been described in this population. We report a case of myocardial infarction in a patient with PHIV with a brief literature review.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sekaggya-Wiltshire2017b,

title = {Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients},

author = { C. Sekaggya-Wiltshire, A. von Braun, A. U. Scherrer, Y. C. Manabe, A. Buzibye, D. Muller, B. Ledergerber, U. Gutteck, N. Corti, A. Kambugu, P. Byakika-Kibwika, M. Lamorde, B. Castelnuovo, J. Fehr, M. R. Kamya},

doi = {https://doi.org/10.1093/jac/dkw534},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {72},

number = {4},

pages = {1172–1177},

abstract = {Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients.



Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients.



Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations.



Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median Cmax of 6.57 (IQR 4.83–9.41) μg/mL, 7.39 (IQR 5.10–10.20) μg/mL, 7.00 (IQR 6.05–10.95) μg/mL and 3.86 (IQR 2.81–14.24) μg/mL, respectively. There was no difference in the median Cmax of rifampicin among those who had hepatotoxicity and those who did not (P = 0.322). There was no difference in the isoniazid median Cmax among those who had peripheral neuropathy 2.34 (1.52–3.23) μg/mL and those who did not 2.21 (1.45–3.11) μg/mL (P = 0.49).



Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.



Topic:

peripheral neuropathy hiv rifampin isoniazid tuberculosis hepatotoxicity toxic effect drug concentration 



},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mujugira2017,

title = {Antiretroviral therapy initiation is not associated with risky sexual behavior among heterosexual HIV-infected persons in serodiscordant partnerships},

author = {Andrew Mujugira, Connie Celum, Kenneth Ngure, Katherine K. Thomas, Elly Katabira, FRCP5 and Jared M. Baeten, for the Partners PrEP Study Team},

doi = {doi: 10.1097/OLQ.0000000000000534},

year  = {2017},

date = {2017-01-01},

journal = {Sex Transm Dis.},

volume = {44},

number = {1},

pages = {57-61},

abstract = {Background



Few prospective studies have assessed whether antiretroviral therapy (ART) use is associated with changes in sexual risk behavior of HIV-infected persons in known HIV-serodiscordant partnerships.



Methods



We conducted a longitudinal analysis of HIV-infected persons with known uninfected partners enrolled in the Partners PrEP Study in Kenya and Uganda. ART use and self-reported sexual behavior were ascertained every 3 months. We assessed the effect of ART on sexual risk behaviors using zero-inflated negative binomial regression. Primary outcomes were condomless vaginal sex acts, pregnancy incidence and new STI diagnoses.



Results



We followed 1817 HIV-infected persons (58% women) for 864 person-years before ART initiation and 771 person-years after ART. Median CD4 and plasma viral load at ART initiation were 277 cells/μL and 4.18 log10 copies/mL. ART use was associated with a significant decrease in condomless vaginal sex acts with HIV-uninfected partners (0.65 vs. 0.39 per month; rate ratio [RR] 0.64; 95% CI: 0.55–0.75; p<0.001), but not condomless vaginal sex acts with non-primary partners (1.30 vs. 1.04 per month; RR 0.94; 95% CI: 0.94–1.20; p=0.62). Pregnancy incidence was lower after ART (13.2 vs 8.4 per 100 person-years; HR 0.71, 95% CI: 0.60–0.84, p<0.001). Incident STI diagnoses were similar (OR 1.05, 95% CI: 0.86–1.29; p=0.63).



Conclusions



Substantial risk compensation did not occur following ART initiation among East African HIV-infected persons with known HIV-uninfected partners. These data inform modeling studies of ART for HIV prevention by suggesting that risky sexual behavior did not appear to offset decreased HIV infectiousness in this key population.



Keywords: HIV, serodiscordant couples, antiretroviral therapy, condomless sex, zero-inflated negative binomial regression},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiggundu2016,

title = {Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy},

author = {Reuben Kiggundu and Henry W Nabetab and Richard Okiab and Joshua Rheina and Robert Lukande},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Unmasking-histoplasmosis-immune-reconstitution-inflammatory-syndrome-in-a-patient-recently-started-on-antiretroviral-therap.pdf},

year  = {2016},

date = {2016-12-30},

journal = {Autopsy Case Reports},

volume = {6},

number = {4},

pages = {27-33},

abstract = {Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions. Keywords Histoplasmosis; Immune Reconstitution Inflammatory Syndrome; Antiretroviral Therapy, Highly Active, Fluconazole

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Manabe2016,

title = {Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial. Am J Trop Med Hyg.},

author = {Yukari C. Manabe and William Worodria and Frank van Leth and Harriet Mayanja-Kizza and Afsatou Ndama Traore and Josefo Ferro and Nadine Pakker and Matthias Frank and Martin P. Grobusch and Robert Colebunders and Frank Cobelens},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Prevention-of-Early-Mortality-by-Presumptive-Tuberculosis-Therapy-Study-An-Open-Label-Randomized-Controlled-Trial.-Am-J-Trop-Med-Hyg..pdf},

doi = {10.4269/ajtmh.16-0239},

year  = {2016},

date = {2016-12-07},

journal = {American Journal of Tropical Medicine and Hygiene},

volume = {95},

number = {6},

pages = {1265-1271},

abstract = { Early mortality after initiation of antiretroviral therapy (ART) occurs in 9–39% of patients in sub-Saharan Africa. A significant proportion of deaths are attributable to tuberculosis (TB). Low baseline CD4 T-cell count and low body mass index (BMI) are strongly associated with early mortality. We hypothesized that initiation of ART concurrent with presumptive anti-TB chemotherapy in high-risk patients would reduce mortality within the first 6 months by treating unrecognized TB. From October 2011 to December 2012, ART-naive, smear-negative participants with a CD4 T-cell count < 50 cells/μL and BMI < 18 kg/m2 were randomly assigned to undergo either empiric four-drug anti-TB treatment followed 2 weeks later by efavirenz-based ART (N = 23) (ART + TB) or ARTonly (N = 20). This open-label, 1:1 randomized, controlled trial took place in Uganda, Mozambique, and Gabon and was stopped prematurely by the sponsor for slow recruitment. Overall, the 43 participants had a median CD4 of 22 (interquartile range [IQR]: 9–35) cells/μL and a median BMI of 17.5 (IQR: 16.6–18.0) kg/m2. The mortality was 14% (95% confidence interval [CI]: 5.3–27.9); two (10.0%) participants (ART-only group), and four (17.4%; ART + TB group). The associated hazard ratio (HR) for all-cause mortality was 1.6 (95% CI: 0.30–8.90). Despite limited enrollment, the study did not suggest that empiric TB treatment in severely immunosuppressed patients with low BMI decreased mortality and, had an HR in the opposite direction than expected. Notably, two participants in the ART + TB group died with autopsy-confirmed drug-induced hepatotoxicity. Improved TB diagnostics sensitive in immunosuppressed patients presenting late to care are urgently needed for more targeted interventions.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuznika2016,

title = {Initiation of antiretroviral therapy based on the 2015 WHO guidelines},

author = {Andreas Kuznika and Garba Iliyasu and Abdulrazaq G. Habib and Baba M. Musa and Andrew Kambugu and Mohammed Lamorde

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Initiation-of-antiretroviral-therapy-based-on-the-2015-WHO-guidelines.pdf},

year  = {2016},

date = {2016-11-28},

journal = {AIDS},

volume = {30},

number = {18},

pages = {2865-2873},

abstract = {Objective:



In 2015, the WHO recommended initiation of antiretroviral therapy (ART) in all HIV-positive patients regardless of CD4+ cell count. We evaluated the cost-effectiveness of immediate versus deferred ART initiation among patients with CD4+ cell counts exceeding 500cells/μl in four resource-limited countries (South Africa, Nigeria, Uganda, and India).

Design:



A 5-year Markov model with annual cycles, including patients at CD4+ cell counts more than 500 cells/μl initiating ART or deferring therapy until historic ART initiation criteria of CD4+ cell counts more than 350 cells/μl were met.

Methods:



The incidence of opportunistic infections, malignancies, cardiovascular disease, unscheduled hospitalizations, and death, were informed by the START trial results. Risk of HIV transmission was obtained from a systematic review. Disability weights were based on published literature. Cost inputs were inflated to 2014 US dollars and based on local sources. Results were expressed in cost per disability-adjusted life years averted and measured against WHO cost-effectiveness thresholds.

Results:



Immediate initiation of ART is associated with a cost per disability-adjusted life years averted of −$317 [95% confidence interval (CI): −$796–$817] in South Africa; −$507 (95% CI: −$765–$837) in Nigeria; −$136 (−$382–$459) in Uganda; and −$78 (−$256–$374) in India. The results are largely driven by the impact of ART on reducing the risk of new HIV transmissions.

Conclusions:



In HIV-positive patients with CD4+ counts above 500 cells/μl in the four studied countries, immediate initiation of ART versus deferred therapy until historic eligibility criteria are met is cost-effective and likely even cost-saving over time.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Russ2016,

title = {Perspectives of host faculty and trainees on international visiting faculty to paediatric academic departments in East Africa},

author = {Christiana M Russ and Lakshmi Ganapathi and Diana Marangu and Melanie Silverman and Edward Kija and Sabrina Bakeera-Kitaka and Ahmed Laving},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Perspectives-of-host-faculty-and-trainees-on-international-visiting-faculty-to-paediatric-academic-departments-in-East-Africa.pdf},

doi = {10.1136/bmjgh-2016-000097},

year  = {2016},

date = {2016-11-14},

journal = {BMJ Global Health},

volume = {1},

number = {3},

abstract = {Background: Investments in faculty exchanges to build physician workforce capacity are increasing. Little attention has been paid to the expectations of host institution faculty and trainees. This prospective qualitative research study explored faculty and resident perspectives about guest faculty in paediatric departments in East Africa, asking (1) What are the benefits and challenges of hosting guest faculty, (2) What factors influence the effectiveness of faculty visits and (3) How do host institutions prepare for faculty visits? Methods: Werecruited36facultymembers and residents from among four paediatric departments in East Africa to participate in semistructured interviews which were audiorecorded andt ranscribed. Datawere qualitatively analysed using principles of opencoding and thematic analysis.We achieved saturation of themes. Results: Benefits of faculty visits varied based on the size and needs of host institutions. Emergent themes included the importance of guest faculty time commitment, and mutual preparation to ensure that visit goals and scheduling met host needs. We documented conflicts that developed around guest emotional responses and ethical approaches to clinical resource limitations, which some hosts tried to prepare for and mitigate. Imbalance in resources led to power differentials; some hosts sought partnerships to reestablish control over the process of having guests. Conclusions: We identified that guest faculty can assist paediatric institutions in building capacity; however, effective visits require: (1) mutually agreed on goals with appropriate scheduling, visit length and commitment to ensure that the visits meet the host’s needs, (2) careful selection and preparation of guest faculty to meet the host’s goals, (3) emotional preparation by prospective guests along with host orientation to clinical work in the host’s setting and (4) attention to funding sources for the visit and mitigation of resulting power differentials.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Manabe2016b,

title = {Human Immunodeficiency Virus-Infected Man With Acute Visual Impairment and Panuveitis Due to Syphilis Despite Initially Negative Rapid Plasma Reagin},

author = {Yukari C. Manabe and August Dietrich and Samuel Kim and Jonathan Zenilman},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/HIV-infected-man-with-acute-visual-impairment-and-panuveitis-due-to-syphilis-despite-initially-negative-RPR.pdf},

doi = {10.1097/OLQ.0000000000000527},

year  = {2016},

date = {2016-11-01},

journal = {Sexually Transmitted Diseases},

volume = {43},

number = {11},

pages = {p.709},

abstract = {We read the article by Marx et al.1 with great interest. We recently admitted a 71-year old man with well-controlled HIV on highly active antiretroviral therapy (324 CD4 cell/mm3 and HIV viral load of <20 copies/mm3) who presented with four months of worsening bilateral blurry vision. Patient reported unprotected sexual encounters with a number of male partners.



On this initial presentation to clinic, he was able to count fingers with the right eye and had 20/63 visual acuity on the left. A retinologist was consulted and diagnosed panuveitis of the right eye and potential acute retinal necrosis on the left. Because of concern for CMV and herpesvirus infection, he was initially treated with oral valcyclovir and intravitreal gancyclovir since he had positive IgM titers to varicella-zoster virus and herpes simplex viruses 1&2. There was modest improvement in his vision. Syphilis anti-treponemal antibody testing was positive, RPR was non-reactive. Urine nucleic acid amplification testing for both gonnorrhea and chlamydia were negative.



Despite 1 month of treatment with anti-virals, the patient’s vision did not improve further, and he presented to us with a one-week history of new bilateral palmar and scrotal rash without lymphadenopathy and a 10 lb weight loss. His repeat RPR was reactive with a titer of 1:2048. The previous non-reactive RPR was retrospectively attributed to a prozone effect. A lumbar puncture was not performed as the patient was on chronic coumadin anticoagulation for a mechanical aortic valve replacement and his INR was >3.0.



He was treated with intravenous penicillin G for two weeks and one week of prednisone with an additional dose of intramuscular penicillin benzathine 2.4 million units on the last day of his treatment. His treatment was complicated by suspected Jarisch-Herxheimer reaction to his initial dose of penicillin with symptoms of chills, fever, and joint pain. The patient has had nearly full recovery of his vision less than two months after completion of his treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katwesigye2016,

title = {Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda},

author = {Elizabeth Katwesigye and Emmanuel Seremba and Fred Semitala and Ponsiano Ocama

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Low-sero-prevalence-of-hepatitis-delta-antibodies-in-HIV-hepatitis-B-co-infected-patients-attending-an-urban-HIV-clinic-in-Uganda.pdf},

doi = {10.4314/ahs.v16i4.26},

year  = {2016},

date = {2016-11-01},

journal = {African Health Sciences},

volume = {16},

number = {4},

pages = {1089-1093},

abstract = {Background:  Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. Methods: We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included.   Results: Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14-6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. Conclusions: The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Roberts2016,

title = {Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study},

author = {Sarah T. Roberts and Jessica Haberer and Connie Celum and Nelly Mugo and Norma C. Ware and Craig R. Cohen and Jordan W. Tappero and James Kiarie and Allan Ronald and Andrew Mujugira and Elioda Tumwesigye and Edwin Were and Elizabeth Irungu and Jared M. Baeten for the Partners PrEP Study Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Intimate-Partner-Violence-and-Adherence-to-HIV-Pre-exposure-Prophylaxis-PrEP-in-African-Women-in-HIV-Serodiscordant-Relationships-A-Prospective-Cohort-Study.pdf},

doi = {  10.1097/QAI.0000000000001093},

year  = {2016},

date = {2016-11-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {73},

number = {3},

pages = {313-322},

abstract = {BACKGROUND:



Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).

METHODS:



We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence.

RESULTS:



Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0-35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away.

CONCLUSIONS:



Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scarsi2016,

title = {Drug-Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV},

author = {Kimberly K. Scarsi and Kristin M. Darin and Catherine A. Chappell and Stephanie M. Nitz and Mohammed Lamorde},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Drug-Drug-Interactions-Effectiveness-and-Safety-of-Hormonal-Contraceptives-in-Women-Living-with-HIV.pdf},

doi = {10.1007/s40264-016-0452-7},

year  = {2016},

date = {2016-11-01},

journal = {Drug Safety},

volume = {39},

number = {11},

pages = {1053-1072},

abstract = {Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with human immunodeficiency virus (HIV) worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{NyegenyeI2016,

title = {Quality assurance as an integral component of diagnostic testing in clinical laboratories and point-of care testing: The Uganda experience},

author = {Wilson Nyegenye and Victor Bigira and Charles Kiyaga and Michael Dfendu and Sam Acellam and Richard Walwema and Lydia Nakiyingi and Isaac Sewanyana and Aida Namakula and Richard Batamwita and William Lali},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Quality-assurance-as-an-integral-component-of-diagnostic-testing-in-clinical-laboratories-and-point-of-care-testing-The-Uganda-experience.pdf},

isbn = {2225-2010},

year  = {2016},

date = {2016-10-17},

journal = {African Journal of Laboratory Medicine},

abstract = {HIV situation in Uganda Uganda, with an estimated population of 35 million people, is a landlocked country that forms part of the East African Union member states. The country is divided into nine political regions (Figure 1), in which there are 112 administrative districts. In order to make the administration and coordination of health services more efficient, the country is further divided into 14 health regions.

Uganda is classified as a high burden HIV country with an estimated 1.6 million people living with HIV/AIDS and 140 000 new cases reported annually (Table 1; Figure 1).1 Being one of only two countries where incidence was on the rise in 2013, HIV remains a major public health problem in Uganda.2 HIV prevalence varies across the country, being highest in the Central region and near urban centres and lowest in the mid-eastern and West Nile regions.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Walter2016,

title = {Adaptation of Mycobacterium tuberculosis to Impaired Host Immunity in HIV-Infected Patients},

author = {Nicholas D. Walter,1,2,4 Bouke C. de Jong,8,16,17 Benjamin J. Garcia,2,5 Gregory M. Dolganov,9 William Worodria,18 Patrick Byanyima and Emmanuel Musisi and Laurence Huang and Edward D. Chan and ran T. Van and Martin Antonio and Abigail Ayorinde and Midori Kato-Maeda and Payam Nahid and Ann M. Leung and Andrew Yen andTasha E. Fingerlin and Katerina Kechris and Michael Strong and Martin I. Voskuil and J. Lucian Davis and Gary K. Schoolnik},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Adaptation-of-Mycobacterium-tuberculosis-to-Impaired-Host-Immunity-in-HIV-Infected-Patients.pdf},

doi = {10.1093/infdis/jiw364},

year  = {2016},

date = {2016-10-15},

journal = {Journal of infectious Diseases},

volume = {214},

number = {8},

pages = {1205-1211},

abstract = {Background. Itisunknownwhether immunosuppressioninfluencesthephysiologicstateofMycobacterium tuberculosisinvivo. We evaluated the impact of host immunity by comparing M. tuberculosis and human gene transcription in sputum between human immunodeficiency virus (HIV)–infected and uninfected patients with tuberculosis. Methods. We collected sputum specimens before treatment from Gambians and Ugandans with pulmonary tuberculosis, revealed by positive results of acid-fast bacillus smears. We quantified expression of 2179 M. tuberculosis genes and 234 human immune genes via quantitative reverse transcription–polymerase chain reaction. We summarized genes from key functional categories with significantly increased or decreased expression. Results. A total of 24 of 65 patients with tuberculosis were HIV infected. M. tuberculosis DosR regulon genes were less highly expressed among HIV-infected patients with tuberculosis than among HIV-uninfected patients with tuberculosis (Gambia, P<.0001; Uganda, P=.037). In profiling of human genes from the same sputa, HIV-infected patients had 3.4-fold lower expression of IFNG (P=.005), 4.9-fold higher expression of ARG1 (P=.0006), and 3.4-fold higher expression of IL10 (P=.0002) than in HIVuninfected patients with tuberculosis. Conclusions. M. tuberculosis in HIV-infected patients had lower expression of the DosR regulon, a critical metabolic and immunomodulatory switch induced by NO, carbon monoxide, and hypoxia. Our human data suggest that decreased DosR expression may result from alternative pathway activation of macrophages, with consequent decreased NO expression and/or by poor granuloma formation with consequent decreased hypoxic stress. Keywords. Mycobacterium tuberculosis/genetics; Mycobacterium tuberculosis/physiology; sputum/microbiology; tuberculosis; pulmonary/epidemiology; acquired immunodeficiency syndrome/immunology.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lund2016,

title = {HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis},

author = {Jennifer M. Lund, Kristina Broliden, Maria N. Pyra, Katherine K. Thomas, Deborah Donnell, Elizabeth Irungu, Timothy R. Muwonge, Show All (15 Authors) , Nelly Mugo, Madhuri Manohar, Marianne Jansson, Romel Mackelprang, Mark A. Marzinke, Jared M. Baeten, Jairam R. Lingappa, for the Partners PrEP Study Show Fewer},

doi = {https://doi.org/10.1128/JVI.01482-16},

year  = {2016},

date = {2016-10-14},

journal = {Journal of Virology},

volume = {90},

number = {21},

abstract = {Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.



IMPORTANCE Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Burnett2016,

title = {Effect of On-Site Support on Laboratory Practice for Human Immunodeficiency Virus, Tuberculosis, and Malaria Testing },

author = {Sarah M. Burnett and Martin K. Mbonye and Robert Martin and Allan Ronald and Stella Zawedde-Muyanja and Kelly S. Willis and Robert Colebunders and Yukari C. Manabe and Marcia R. Weaver

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Effect-of-On-Site-Support-on-Laboratory-Practice-for-Human-Immunodeficiency-Virus-Tuberculosis-and-Malaria-Testing-.pdf},

doi = {10.1093/ajcp/aqw138},

year  = {2016},

date = {2016-10-03},

journal = {American Journal of Tropical Medicine and Hygiene},

volume = {146},

number = {4},

pages = {469-477},

abstract = {Objectives: To evaluate the effect of on-site support in improving human immunodeficiency virus (HIV) rapid testing, tuberculosis (TB) sputum microscopy, and malaria microscopy among laboratory staff in a low-resource setting.



Methods: This cluster randomized trial was conducted at 36 health facilities in Uganda. From April to December 2010, laboratory staff at 18 facilities participated in monthly on-site visits, and 18 served as control facilities. After intervention, 128 laboratory staff were observed performing 587 laboratory tests across three diseases: HIV rapid testing, TB sputum microscopy, and malaria microscopy. Outcomes were the proportion of laboratory procedures correctly completed for the three laboratory tests.



Results: Laboratory staff in the intervention arm performed significantly better than the control arm in correctly completing laboratory procedures for all three laboratory tests, with an adjusted relative risk (95% confidence interval) of 1.18 (1.10-1.26) for HIV rapid testing, 1.29 (1.21-1.40) for TB sputum microscopy, and 1.19 (1.11-1.27) for malaria microscopy.



Conclusions: On-site support significantly improved laboratory practices in conducting HIV rapid testing, TB sputum microscopy, and malaria microscopy. It could be an effective method for improving laboratory practice, without taking limited laboratory staff away from health facilities for training. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rhein2016c,

title = {Sertraline for HIV-associated cryptococcal meningitis - Authors' reply},

author = { Joshua Rhein and Kirsten Nielsen and David R Boulware and David B Meya},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Sertraline-for-HIV-associated-cryptococcal-meningitis.pdf},

doi = {doi.org/10.1016/S1473-3099(16)30340-1},

year  = {2016},

date = {2016-10-01},

journal = {Lancent Infectious Diseases},

volume = {16},

number = {10},

pages = {1111-1112},

abstract = {We agree with Anette Veringa and colleagues regarding the importance of pharmacological analyses in the assessment of antifungal efficacy for cryptococcal meningitis treatment. Yet, we caution the translation of single-drug pharmacological analyses to combination therapy. Fluconazole 800 mg/day monotherapy as induction therapy for cryptococcal meningitis has poor outcomes: fluconazole's area under the curve (AUC) exposure is suboptimal with respect to the cryptococcus minimum inhibitory concentration (MIC).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakku-Joloba2016,

title = {Clinical Evaluation of 2 Point-of-Care Lateral Flow Tests for the Diagnosis of Syphilis},

author = {Edith Nakku-Joloba and Agnes Kiragga and Joshua Kimeze Mbazira and Fred Kambugu and Mary Jett-Goheen and Rosalind Parkes Ratanshi and Charlotte Gaydos and Yukari C. Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Clinical-Evaluation-of-Two-Point-Of-Care-Lateral-Flow-Tests-for-the-Diagnosis-of-Syphilis.pdf},

doi = {10.1097/OLQ.0000000000000498},

year  = {2016},

date = {2016-10-01},

journal = {HHS Public Access},

volume = {43},

number = {10},

pages = {623-625},

abstract = {A diagnostic performance study comparing the only Food and Drug Administration (FDA)approved, point-of-care (POC) treponemal test (Syphilis Health Check) and the World Health organization (WHO)-pre-qualified SD Bioline POC treponemal test against a treponemal hemagglutination test (TPHA) and a sequential algorithm of non-treponemal rapid plasma reagin (RPR) and TPHA found both POC tests had >85% sensitivity compared with the TPHA and >85% sensitivity and >95% specificity compared with the RPR and TPHA standards.

Single-step, rapid, point-of-care (POC) tests provide results in under 30 minutes and improves access to care for many infectious diseases including syphilis [1]. Development and validation of newer POC tests may accelerate timely treatment since RPR testing requires a working laboratory with electricity. Syphilis testing is especially important for pregnant women where 53.4–81.8% had adverse outcomes including stillbirth and congenital syphilis in a recent meta-analysis.[2] The WHO has recommended the use of POC rapid tests for syphilis [3, 4]; in countries with a high prevalence (3–5%) as in Uganda, syphilis tests should be more than 85% sensitive and more than 95% specific. [4].

A number of POC rapid tests for syphilis are now available in Uganda on the open market including the WHO pre-qualified SD Bioline (Yonghi Cho, Korea Kyogghi Do, Korea), the ABON Syphilis Ultra Rapid test strip (Wellkang Ltd, London UK), rapid chromatographic immunoassays for the qualitative detection of treponemal antibodies (IgG and IgM) in whole blood, serum or plasma. The recently FDA-approved, CLIA-waived Syphilis Health Check (Trinity Biotech, USA) is a qualitative, rapid treponemal membrane immunochromatographic lateral flow assay. Prior evaluations of the Syphilis Health Check have only been done in US populations, so more data on the performance of this syphilis POC test in African populations with higher prevalence is needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Semeere2016,

title = {Innovative Demand Creation for Voluntary Medical Male Circumcision Targeting a High Impact Male Population: A Pilot Study Engaging Pregnant Women at Antenatal Clinics in Kampala, Uganda},

author = {Aggrey S. Semeere, MBChB, MMed, MAS, Barbara Castelnuovo, MD, PhD, Denis S. Bbaale, MBChB, MMS, PGD (PPM), Agnes N. Kiragga and Joanita Kigozi and Alex M. Muganzi and Alex G. Coutinho and Andrew Kambugu 

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Innovative-Demand-Creation-for-Voluntary-Medical-Male-Circumcision-Targeting-a-High-Impact-Male-Population-A-Pilot-Study-Engaging-Pregnant-Women-at-Antenatal-Clinics-in-Kampala-Uganda.pdf},

doi = {10.1097/QAI.0000000000001041},

year  = {2016},

date = {2016-10-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {4},

pages = {278-284},

abstract = {Background: Circumcision has been shown to be an effective method of HIV prevention; however, only 28% of Ugandan men aged 15–49 years are circumcised. There is a paucity of data on the role of intimate partners in generating demand for voluntary medical male circumcision (VMMC). We conducted a pilot study to assess the feasibility of a partner-focused intervention targeting males .25 years. Methods: Among pregnant women in their third trimester attending antenatal care we evaluated the impact of a pilot behavior change intervention on VMMC through a quasi-experimental approach. We observed VMMC numbers among spouses of women as per standard practice (comparison phase), and after introducing a behavioral change communication package (intervention phase). Logistic regression was used to compare the odds of VMMC uptake between comparison and intervention phases. We used qualitative methods to evaluate the casual chain using a thematic approach. Results: Of the 601 women studied, 90% articulated the health benefits of VMMC and 99% expressed interest in their spouse getting circumcised. Women’s knowledge was not increased by the intervention. Four men were circumcised in the comparison and 7 in the intervention phase. The intervention was not associated with higher odds of circumcision (odds ratio 1.5, 95% CI: 0.3 to 6.0, P = 0.65). We interviewed 117 individuals overall with the main enablers for VMMC being: free VMMC, transport reimbursement, and health benefits. Deterrents included misconceptions, lost wages and fear of pain. Most of the uncircumcised men interviewed reported interest in VMMC.

Conclusions: Our pilot intervention had no significant impact on increasing VMMC demand. The study demonstrated the feasibility of pregnant women engaging their spouses to discuss VMMC.

Key Words: voluntary medical male circumcision, pregnant women

(J Acquir Immune Defic Syndr 2016;72:S278–S284)

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mugwanya2016c,

title = {Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption},

author = {Kenneth K. Mugwanya, Craig W. Hendrix, Nelly R. Mugo, Mark Marzinke, Elly T. Katabira, Kenneth Ngure, Nulu B. Semiyaga, Grace John-Stewart, Timothy R. Muwonge, Gabriel Muthuri, Andy Stergachis, Connie L. Celum, Jared M. Baeten},

doi = {doi.org/10.1371/journal.pmed.1002132},

year  = {2016},

date = {2016-09-27},

journal = {PLOS MEDICINE},

volume = {13},

number = {9},

pages = { e1002132},

abstract = {Background



As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.



Methods and Findings



We conducted a prospective short-term, open-label study of daily oral emtricitabine–tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother–infant pairs between 1–24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1–2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.



Of the 50 mother–infant pairs enrolled, 48% were ≤12 wk and 52% were 13–24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22–28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the ≤12 weeks, and 14 (12 to 17) for the 13–24 wk infant age groups. Overall, median (IQR) time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 μg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up.



The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk.



Conclusion



In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure.



Trial Registration



ClinicalTrials.gov, Identifier: NCT02776748

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orikiiriza2016,

title = {Rollout of efavirenz-based regimens in option B+ in the prevention of mother-to-child transmission programs: challenges and lessons learned from a postexposure prophylaxis experience},

author = {Judy T. Orikiiriza},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Rollout-of-efavirenz-based-regimens-in-option-B-in-the-prevention-of-mother-to-child-transmission-programs-challenges-and-lessons-learned-from-a-postexposure-prophylaxis-experience.pdf},

doi = {10.1097/QAD.0000000000001212},

year  = {2016},

date = {2016-09-24},

volume = {30},

number = {15},

pages = {29-31},

abstract = {The standard of care for individuals exposed to HIV is to administer antiretroviral drugs to prevent HIV infection. Examples include healthcare workers (HCWs) who sustain injuries from occupational exposure [1]. This is commonly referred to as postexposure prophylaxis (PEP) for HIV infection and is administered for 1 month.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nielsen2016,

title = {Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs},

author = {Kirsten Nielsen and Priya Vedula and Kyle D. Smith and David B. Meya and Edward P. Garvey and William J. Hoekstra and Robert J. Schotzinger and David R. Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Activity-of-VT-1129-against-Cryptococcus-neoformans-clinical-isolates-with-high-fluconazole-MICs.pdf},

doi = {10.1093/mmy/myw089},

year  = {2016},

date = {2016-09-24},

journal = {Medical Mycology},

volume = {55},

number = {4},

pages = {453-456},

abstract = {Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16–32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jones-López2016,

title = {Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics. },

author = {Edward C. Jones-López and Laura F.White and Bruce Kirenga and Francis Mumbowa and Martin Ssebidandi and Stephanie Moine and Olive Mbabazi and Gerald Mboowa and IreneAyakaka and Soyeon Kim and Christina S. Thornton and Alphonse Okwera and Moses Joloba Kevin P. Fennelly

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Cough-Aerosol-Cultures-of-Mycobacterium-tuberculosis-Insights-on-TST-IGRA-Discordance-and-Transmission-Dynamics.pdf},

doi = {10.1371/journal.pone.0138358},

year  = {2016},

date = {2016-09-22},

journal = {PloS One},

volume = {10},

number = {9},

abstract = {RATIONALE:



The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10-20% of individuals, but the underlying mechanisms are poorly understood.

METHODS:



We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.

MEASUREMENTS AND RESULTS:



We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02-1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99-1.98, p = 0.06).

CONCLUSIONS:



We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Auld2016,

title = {HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis. },

author = {Elizabeth Auld and Jue Lin and Emily Chang and Patrick Byanyima and Irene Ayakaka and Emmanuel Musisi and William Worodria and J. Lucian Davis and Mark Segal and Elizabeth Blackburn and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/HIV-Infection-Is-Associated-with-Shortened-Telomere-Length-in-Ugandans-with-Suspected-Tuberculosis.pdf},

doi = {10.1371/journal.pone.0163153},

year  = {2016},

date = {2016-09-21},

journal = {PloS One},

volume = {11},

number = {9},

abstract = {HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality.

METHODS:



This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models.

RESULTS:



No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001), male gender (P = 0.04), total pack-years smoked (P<0.001), alcohol consumption in the past year (P = 0.12), and asthma (P = 0.08) were all associated (P≤0.2) with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02). Shortened telomeres were not associated with TB or short-term mortality.

CONCLUSIONS:



The association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Opio2016,

title = {Profiling lifetime episodes of upper gastrointestinal bleeding among patients from rural Sub-Saharan Africa where schistosoma mansoni is endemic.},

author = {Christopher Kenneth Opio and Francis Kazibwe and Ponsiano Ocama and Lalitha Rejani and Elena Nikolaevna Belousova and Paul Ajal },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Profiling-lifetime-episodes-of-upper-gastrointestinal-bleeding-among-patients-from-rural-Sub-Saharan-Africa-where-schistosoma-mansoni-is-endemic..pdf},

doi = {10.11604/pamj.2016.24.296.9755},

year  = {2016},

date = {2016-09-03},

journal = {Pan African Medical Journal},

volume = {24},

abstract = {Introduction: Severe chronic hepatic schistosomiasis is a common cause of episodes upper gastrointestinal bleeding (UGIB) in sub-Saharan Africa (SSA). However, there is paucity of data on clinical epidemiology of episodes of UGIB from rural Africa despite on going public health interventions to control and eliminate schistosomiasis. Methods: Through a cross sectional study we profiled lifetime episodes of upper gastrointestinal bleeding and associated factors at a rural primary health facility in sub-Saharan Africa were schistosomiasis is endemic. The main outcome was number of lifetime episodes of UGIB analyzed as count data. Results: From 107 enrolled participants, 323 lifetime episodes of UGIB were reported. Fiftyseven percent experienced ≥ 2 lifetime episodes of UGIB. Ninety-four percent had severe chronic hepatic schistosomiasis and 80% esophageal varices. Alcohol use and viral hepatitis was infrequent. Eighty-eight percent were previously treated with praziquantel and 70% had a history of blood transfusion. No patient had ever had an endoscopy or treatment for prevention of recurrent variceal bleeding. Multivariable analysis identified a cluster of eight clinical factor variables (age ≥ 40, female sex, history of blood transfusion, abdominal collaterals, esophageal varices, pattern x periportal fibrosis, anemia, and thrombocytopenia) significantly associated (P-value < 0.05) with increased probability of experiencing two or more lifetime episodes of UGIB in our study. Conclusion: Upper gastrointestinal bleeding is a common health problem in this part of rural SSA where schistosomiasis is endemic. The clinical profile described is unique and is important for improved case management, and for future research. 

 

 },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kakaire2016,

title = {The future of financing for HIV services in Uganda and the wider sub-Saharan Africa region: should we ask patients to contribute to the cost of their care? },

author = {Tom Kakaire and Walter Schlech and Alex Coutinho and Richard Brough and Rosalind Parkes-Ratanshi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-future-of-financing-for-HIV-services-in-Uganda-and-the-wider-sub-Saharan-Africa-region-should-we-ask-patients-to-contribute-to-the-cost-of-their-care.pdf},

doi = {10.1186/s12889-016-3573-0.},

year  = {2016},

date = {2016-08-27},

journal = {BMC Public Health},

volume = {16},

number = {1},

abstract = {Whilst multi-lateral funding for HIV/AIDS dramatically increased from 2004 to 2008, it has largely plateaued in the last 8 years. Across sub-Saharan Africa, up to 20 % of total spending on health is used for HIV services, and of this over 85 % is estimated to come from international funding rather than in-country sources. In Uganda, the fiscal liability to maintain services for all those who are currently receiving it is estimated to be as much as 3 % of Gross Domestic Product (GDP). In order to meet the growing need of increased patient numbers and further ART coverage the projected costs of comprehensive HIV care and treatment services will increase substantially. Current access to HIV care includes free at point of delivery (provided by Ministry of Health clinics), as well as out-of-pocket financing and health insurance provided care at private for- and not for- profit facilities. The HIV response is funded through Ugandan Ministry of Health national budget allocations, as well as multilateral donations such as the President’s Emergency Plan for AIDS in Africa (PEPFAR) and Global Fund (GF) and other international funders. We are concerned that current funding mechanism for HIV programs in Uganda may be difficult to sustain and as service providers we are keen to explore ways in which provide lifelong HIV care to as many people living with HIV (PLHIV) as possible. Until such time as the Ugandan economy can support universal, state-supported, comprehensive healthcare, bridging alternatives must be considered. We suggest that offering patients with the sufficient means to assume some of the financial burden for their care in return for more convenient services could be one component of increasing coverage and sustaining services for those living with HIV. Keywords: Financing, Sustaining, Uganda, HIV, Treatment

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Baeten2016,

title = {Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.},

author = {Jared M. Baeten and Renee Heffron and Lara Kidoguchi and Nelly R. Mugo and EllyKatabira and Elizabeth A. Bukusi and Stephen Asiimwe and Jessica E. Haberer and Jennifer Morton and Kenneth Ngure and Nulu Bulya and Josephine Odoyo and Edna Tindimwebwa and Craig Hendrix and Mark A. Marzinke and Norma C. Ware and Monique A. Wyatt and Susan Morrison and Harald Haugen and Andrew Mujugira and Deborah Donnell and Connie Celum and ,Partners Demonstration Project Team 

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Integrated-Delivery-of-Antiretroviral-Treatment-and-Pre-exposure-Prophylaxis-to-HIV-1–Serodiscordant-Couples-A-Prospective-Implementation-Study-in-Kenya-and-Uganda.pdf},

doi = {10.1371/journal.pmed.1002099},

year  = {2016},

date = {2016-08-23},

journal = {PloS Medicine},

volume = {13},

number = {8},

abstract = {Background



Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.

Go to:

Methods and Findings



Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.

Go to:

Conclusions



Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A2016c,

title = {HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy},

author = {Mujugira A and Celum C and Coombs RW, Campbell JD and Ndase P and Ronald A and Were E and Bukusi EA and Mugo N and Kiarie J and Baeten JM and Partners PrEP Study Team.},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/HIV-Transmission-Risk-Persists-During-the-First-6-Months-of-Antiretroviral-Therapy.pdf},

doi = {10.1097/QAI.0000000000001019},

year  = {2016},

date = {2016-08-15},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {5},

pages = {579-584},

abstract = {OBJECTIVE:



Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression.

DESIGN:



Prospective cohort study.

METHODS:



Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and generalized estimating equations logistic regression.

RESULTS:



The cumulative probabilities of achieving blood viral suppression (<80 copies per milliliter) 3, 6, and 9 months after ART initiation were 65.3%, 84.8%, and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6 months of ART. Pregnancy incidence was 8.8 per 100 person-years during the first 6 months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0-6 months after ART initiation (3 infections; 168 person-years), and 0.00 with >6 months of ART (0 infections; 167 person-years).

CONCLUSIONS:



Residual HIV transmission risk persists during the first 6 months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2016b,

title = {Different modalities of entry in a large urban clinic in Uganda and impact on outcomes of patients assessing HIV care and treatment},

author = {Barbara Castelnuovo, Rachel Musomba, Joseph Musaazi & Agnes N. Kiragga

},

doi = {https://doi.org/10.1080/09540121.2016.1211604},

year  = {2016},

date = {2016-08-15},

journal = { AIDS Care,  Psychological and Socio-medical Aspects of AIDS/HIV },

volume = {29},

number = {2},

pages = {259-262},

abstract = {In resource-limited settings, a number of patients do not receive continuous HIV care. In this analysis, we compared outcomes in patients who entered care by different modality of entry. This was a retrospective analysis of all patients started on antiretroviral treatment (ART) at a large urban center in Uganda from 2005 to 2012. Patients were categorized into three groups (1) Front door: started on ART without interruption during follow-up; (2) drop-out side door: restarted on ART after having an interruption >6 months and (3) transfer-in side door: transferred-in after being started on ART somewhere else. We compared characteristics at enrollment in the three groups and investigated the following outcomes: (1) retention in care (2) switch to second line. In the study period 11,528 (87.2%) were enrolled through the front door, 1159 (8.7%) resumed ART after dropping out, while 527 (4%) patients were transferred in on ART. The three groups were generally comparable, although patients transferred in were sicker. A larger proportion of patients entered through the drop-out side door died or was lost to follow-up (37.3%), as compared to patients in the front door group (24.9%) and transferred-in side door group (17.7%). More patients in the front door group (32.1%) were transferred out during the follow-up. The highest probability of switching to second line was found in the transferred-in group. Patients who re-enter our program after dropping out are at higher risk of dropping out of care and often need to be switched to second-line ART. The high demand for second-line therapy among patients in transfer-in side door reflects failure in management of complicated patients who are usually require “up-transfer” to better treatment centers. In future understanding, the different modes of entry into HIV care will be key in reshaping the general cascade of HIV care.



KEYWORDS: HIV carecascadeenrollmentantiretroviral treatment“front door”“side door”},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rachlis2016,

title = {Facility-Level Factors Influencing Retention of Patients in HIV Care in East Africa.},

author = {Beth Rachlis and Giorgos Bakoyannis and Philippa Easterbrook and Becky Genberg and Ronald Scott Braithwaite and Craig R.Cohen and Elizabeth A. Bukusi and Andrew Kambugu and Mwebesa Bosco Bwana and Geoffrey R. Somi and Elvin H. Geng and Beverly Musick Constantin T.Yiannoutsos KaraWools-Kaloustian and Paula Braitstein 

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Facility-Level-Factors-Influencing-Retention-of-Patients-in-HIV-Care-in-East-Africa..pdf},

doi = {10.1371/journal.pone.0159994},

year  = {2016},

date = {2016-08-10},

volume = {11},

number = {8},

abstract = {Losses to follow-up (LTFU) remain an important programmatic challenge. While numerous patient-level factors have been associated with LTFU, less is known about facility-level factors. Data from the East African International epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium was used to identify facility-level factors associated with LTFU in Kenya, Tanzania and Uganda. Patients were defined as LTFU if they had no visit within 12 months of the study endpoint for pre-ART patients or 6 months for patients on ART. Adjusting for patient factors, shared frailty proportional hazard models were used to identify the facility-level factors associated with LTFU for the pre- and post-ART periods. Data from 77,362 patients and 29 facilities were analyzed. Median age at enrolment was 36.0 years (Interquartile Range: 30.1, 43.1), 63.9% were women and 58.3% initiated ART. Rates (95% Confidence Interval) of LTFU were 25.1 (24.7-25.6) and 16.7 (16.3-17.2) per 100 person-years in the pre-ART and post-ART periods, respectively. Facility-level factors associated with increased LTFU included secondary-level care, HIV RNA PCR turnaround time >14 days, and no onsite availability of CD4 testing. Increased LTFU was also observed when no nutritional supplements were provided (pre-ART only), when TB patients were treated within the HIV program (pre-ART only), and when the facility was open ≤4 mornings per week (ART only). Our findings suggest that facility-based strategies such as point of care laboratory testing and separate clinic spaces for TB patients may improve retention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuznik2016,

title = {Newborn screening and prophylactic interventions for sickle cell disease in 47 countries in sub-Saharan Africa: a cost-effectiveness analysis. },

author = {Andreas Kuznik and Abdulrazaq G. Habib and Deogratias Munube and Mohammed Lamorde},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Newborn-screening-and-prophylactic-interventions-for-sickle-cell-disease-in-47-countries-in-sub-Saharan-Africa-a-cost-effectiveness-analysis.pdf},

doi = { 10.1186/s12913-016-1572-6},

year  = {2016},

date = {2016-07-26},

journal = {BMC Health Services Research},

volume = {16},

number = {1},

pages = {p.304},

abstract = {Background: Sickle cell disease (SCD) constitutes a major public health problem in sub-Saharan Africa (SSA). Newborn screening and early subsequent clinical intervention can reduce early mortality and increase life expectancy, but have not been widely implemented in SSA. This analysis assesses the cost-effectiveness of a newborn screening and prophylactic intervention (NSPI) package for SCD in 47 SSA countries. Methods: A lifetime Markov model with annual cycles was built with infants either being screened using isoelectric focusing (IEF) or not screened. Confirmed positive cases received interventions including insecticide-treated mosquito bed nets, folic acid supplementation, prophylactic antimalarial and penicillin therapy, and vaccinations against bacterial infections. Estimates for the local incidence of SCD, the life expectancy of untreated children, the SCD disability weight, and the cost of screening laboratory tests were based on published sources. Among treated infants, the annual probability of mortality until 30 years of age was derived from a pediatric hospital-based cohort. The outcome of interest included a country-specific cost per Disability Adjusted Life Year (DALY) averted. Results: Of 47 modeled countries in SSA, NSPI is almost certainly highly cost-effective in 24 countries (average cost per DALY averted: US$184); in 10 countries, it is cost-effective in the base case (average cost per DALY averted: US$285), but the results are subject to uncertainty; in the remaining 13, it is most likely not cost-effective. We observe a strong inverse relationship between the incidence rate of SCD and the cost per DALY averted. Newborn screening is estimated to be cost-effective as long as the incidence rate exceeds 0.2–0.3 %, although in some countries NSPI is cost-effective at incidence rates below this range. In total, NSPI could avert over 2.4 million disability adjusted life years (DALYs) annually across SSA. Conclusions: Using IEF to screen all newborns for SCD plus administration of prophylactic interventions to affected children is cost-effective in the majority of countries in SSA. Keywords: Anaemia, Sickle cell, Cost-effectiveness analysis, Neonatal screening, Africa

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shenoy2016,

title = {Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in HIV-Pneumonia Patients},

author = {Meera K. Shenoy, Shoko Iwai, Din L. Lin, William Worodria, Irene Ayakaka, Patrick Byanyima, Sylvia Kaswabuli, Serena Fong, Stephen Stone, Emily Chang, J. Lucian Davis, Ali Ahmad Faruqi, Mark R. Segal, Laurence Huang and Susan V. Lynch },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Immune-Response-and-Mortality-Risk-Relate-to-Distinct-Lung-Microbiomes-in-Patients-with-HIV-and-Pneumonia..pdf},

doi = { 10.1164/rccm.201603-0523OC},

year  = {2016},

date = {2016-07-22},

journal = {American Journal of Repository and Critical Care Medicine},

volume = {195},

number = {1},

pages = {104-114},

abstract = {Rationale: The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown. Objectives: To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality. Methods: Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n=182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected. Lower airway bacterial communitycomposition was assessed via amplification and sequencing of the V4 region of the 16S ribosomal RNA gene. Host immune response gene expression profiles were generated by quantitative polymerase chain reaction using RNA extracted from bronchoalveolar lavage fluid. Liquid and gas chromatography mass spectrometry was used to profile serum metabolites.

Measurements and Main Results: Based on airway microbiome composition, most patients segregated into three distinct groups, each of which were predicted to encode metagenomes capable of producing metabolites characteristically enriched in paired serum samples from these patients.These three groups also exhibited differences inmortality;those with the highest ratehad increased ceftriaxone administration and culturableAspergillus,and demonstrated significantlyincreasedinductionofairwayT-helpercelltype2responses. The group with the lowes tmortality was characterized by increased expressionofT-cellimmunoglobulinandmucindomain3,which down-regulates T-helpercelltype1proinflammatoryresponsesand is associated withchronicviralinfection. Conclusions: These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality. Keywords: HIV; microbiota; pneumonia; immune response; mortality

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Prendergast2016,

title = {Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy. },

author = {Andrew J. Prendergast and Alexander J. Szubert and Chipo Berejena and Godfrey Pimundu and Pietro Pala and Annie Shonhai and Victor Musiime and Mutsa Bwakura-Dangarembizi and Hannah Poulsom and Patricia Hunter and Philippa Musoke and Macklyn Kihembo and Paula Munderi and Diana M. Gibb and Moira Spyer and A. Sarah Walker and Nigel Klein the ARROW Trial Teamb },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Baseline-Inflammatory-Biomarkers-Identify-Subgroups-of-HIV-Infected-African-Children-With-Differing-Responses-to-Antiretroviral-Therapy..pdf},

doi = { 10.1093/infdis/jiw148},

year  = {2016},

date = {2016-07-15},

journal = {Journal of infectious Diseases},

volume = {214},

number = {2},

pages = {226-236},

abstract = {Background. Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)–infected children. Methods. CD4+ T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART. Results. There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4–11.4 years) and 5.8 years (IQR, 2.3–9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%–9%) and 13% (IQR, 8%–18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4+ T-cell count ratio (calculated asthe ratio of the subject’s CD4+ T-cell count to the count expected in healthy individuals of the sameage;P<.0001)andhigherIL-6level (P=.002)thancontrols.Clusteringbiomarkersandage-associatedCD4+ andCD8+ T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8+ T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died). Conclusions. While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes. Keywords. HIV; Africa; children; inflammation; immunosuppression.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Osingada2016,

title = {Prevalence, barriers and factors associated with parental disclosure of their HIV positive status to children: a cross-sectional study in an urban clinic in Kampala, Uganda},

author = {Charles Peter Osingada and Monica Okuga and Rose Chalo Nabirye abd Nelson Kaulukusi Sewankambo and Damalie Nakanjako

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Prevalence-barriers-and-factors-associated-with-parental-disclosure-of-their-HIV-positive-status-to-children-a-cross-sectional-study-in-an-urban-clinic-in-Kampala-Uganda.pdf},

doi = {10.1186/s12889-016-3235-2},

year  = {2016},

date = {2016-07-11},

journal = {BMC Public Health},

volume = {16},

pages = {p.547},

abstract = {Background: Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children. Methods: A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1. Results: Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent’s HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status. Conclusions: Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level. Keywords: HIV Disclosure, Prevalence, Barriers, Associated factors, Uganda

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dirix2016,

title = {Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda. },

author = {Violette Dirix and Kinda Schepers and Marguerite Massinga-Loembe and William Worodria and Robert Colebunders and Mahavir Singh and Camille Locht and Luc Kestens and Françoise Mascart and TB-IRIS study group

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Added-Value-of-Long-Term-Cytokine-Release-Assays-to-Detect-Mycobacterium-tuberculosis-Infection-in-HIV-Infected-Subjects-in-Uganda.pdf},

doi = { 10.1097/QAI.0000000000000980},

year  = {2016},

date = {2016-07-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {2},

pages = {344-352},

abstract = {OBJECTIVES:



To investigate whether mycobacterial antigen-induced cytokine secretions are helpful in detecting Mycobacterium tuberculosis (Mtb) infection in a cohort of HIV-infected patients living in a country with a high burden of Mtb and HIV infections, and to determine their predictive value for the development of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome.

DESIGN:



A total of 352 HIV-infected patients (186 with active TB) were prospectively enrolled when initiating antiretroviral therapy (ART). Sequential blood samples were collected during the first 6 months of ART. Eighty-three HIV-uninfected subjects (39 with active TB) were enrolled as controls.

METHODS:



The concentrations of 13 cytokines were measured in supernatants from blood mononuclear cells in vitro stimulated with purified protein derivative (PPD), heparin-binding hemagglutinin (HBHA) or early secreted antigen-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), and results were compared with those of tuberculin skin tests (TST).

RESULTS:



The best detection of Mtb infection was achieved by ESAT-6/CFP-10-induced interferon-γ concentrations, but results were often negative for patients with CD4 T-cell counts <50 per cubic millimeters. Patients with active TB were identified by high ESAT-6/CFP-10-induced interleukin-6. Conversions of interferon-γ-release assays (IGRA) and TST occurred under ART, and combined TB and antiretroviral treatments of coinfected patients resulted in a decrease of ESAT-6/CFP-10-induced and an increase of HBHA-induced interferon-γ responses. No Mtb antigen-induced cytokines allowed us to predict TB-immune reconstitution inflammatory syndrome or ART-associated TB.

CONCLUSIONS:



In Uganda, ESAT-6/CFP-10-IGRA is better in detecting Mtb infection than TST and, when combined with an HBHA-IGRA, could help to evaluate anti-TB treatment success.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katagira2016,

title = {Empiric TB treatment of severely ill patients with HIV and presumed pulmonary TB improves survival},

author = {Winceslaus Katagira, Nicholas D. Walter, Saskia den Boon, Nelson Kalema, Irene Ayakaka, Eric Vittinghoff, William Worodria, Adithya Cattamanchi, Laurence Huang and J. Lucian Davis},

doi = {doi: 10.1097/QAI.0000000000000970},

year  = {2016},

date = {2016-07-01},

journal = {J Acquir Immune Defic Syndr.},

volume = {72},

number = {3},

pages = {297–303},

abstract = {Rationale



In 2007, WHO issued emergency recommendations on empiric treatment of sputum acid-fast bacillus (AFB) smear-negative patients with possible tuberculosis (TB) in HIV-prevalent areas, and called for operational research to evaluate their effectiveness. We sought to determine if early, empiric TB treatment of possible TB patients with abnormal chest radiography or severe illness as suggested by the 2007 WHO guidelines is associated with improved survival.



Methods



We prospectively enrolled consecutive HIV-seropositive inpatients at Mulago Hospital in Kampala, Uganda, from 2007 to 2011 with cough ≥2 weeks. We retrospectively examined the effect of empiric TB treatment before discharge on eight-week survival among those with and without a WHO-defined “danger sign,” including fever >39°C, tachycardia >120 beats-per-minute, or tachypnea >30 breaths-per-minute. We modeled the interaction between empiric TB treatment and danger signs and their combined effect on eight-week survival and adjusted for relevant covariates.

Results



Among 631 sputum smear-negative patients, 322(51%) had danger signs. Cumulative eight-week survival of patients with danger signs was significantly higher with empiric TB treatment(80%) than without(64%, p<0.001). After adjusting for duration of cough and concurrent hypoxemia, patients with danger signs who received empiric TB treatment had a 44% reduction in eight-week mortality(Risk Ratio 0.54, 95%CI 0.32-0.91, p=0.020).



Conclusions



Empiric TB treatment of HIV-seropositive, smear-negative, presumed pulmonary TB patients with one or more danger signs is associated with improved eight-week survival. Enhanced implementation of the 2007 WHO empiric-treatment recommendations should be encouraged whenever and wherever rapid and highly sensitive diagnostic tests for TB are unavailable.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2016,

title = {First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda.},

author = {Barbara Castelnuovo and Agnes Kiragga and Frank Mubiru and Andrew Kambugu and Moses Kamya and Steven J Reynolds },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/First-line-antiretroviral-therapy-durability-in-a-10-year-cohort-of-naïve-adults-started-on-treatment-in-Uganda-2.pdf},

doi = {doi.org/10.7448/IAS.19.1.20773},

year  = {2016},

date = {2016-06-17},

journal = {Journal Of The International AIDS Society},

volume = {19},

number = {1},

abstract = {Introduction



The majority of studies from resource‐limited settings only report short‐term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long‐term durability of first‐line ART and identify factors associated with long‐term virological outcomes.



Methods



At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time‐dependent CD4 count and adherence.

Results



Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow‐up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz‐based group. Four hundred thirty‐nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five‐year increase; CI: 0.77–0.99), with adherence >95% (HR: 0.04; CI: 0.02–0.11) and with higher time‐dependent CD4 count (HR: 0.94 per 50 cells/µl increase; CI: 0.92–0.99, p<0.001) were less likely to experience treatment failure.



Conclusions



The long‐term virological outcomes from this cohort are promising and comparable to those from research‐rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ousman2016,

title = {Interprofessional Fellowship Training for Emerging Global Health Leaders in Africa to Improve HIV Prevention and Care: The Afya Bora Consortium. },

author = {Kevin Ousman and Rosemary C. Polomano and Esther Seloilwe and Theresa Odero and Edith Tarimo and Yohana J. Mashalla and Joachim G. Voss and Gabrielle O’Malley and Susan A. Chapman and Onesmus Gachumo and Yukari Manabe and Damalie Nakanjako and Nelson Sewankambo and David Urassa and Judith N. Wasswrheit and Douglas J. Wiebe and Wendy Green and Carey Farquhar and Afya Bora Consortium Working Group},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Interprofessional-Fellowship-Training-for-Emerging-Global-Health-Leaders-in-Africa-to-Improve-HIV-Prevention-and-Care-The-Afya-Bora-Consortium..pdf},

doi = {10.1016/j.jana.2016.01.009},

year  = {2016},

date = {2016-06-07},

journal = {Journal of the Association of Nurses in AIDS care},

volume = {27},

number = {3},

pages = {331-343},

abstract = {HIV continues to challenge health systems, especially in low- and middle-income countries in Sub-Saharan Africa. A qualified workforce of transformational leaders is required to strengthen health systems and introduce policy reforms to address the barriers to HIV testing, treatment, and other HIV services. The 1-year Afya Bora Consortium Fellowship in Global Health capitalizes on academic partnerships between African and U.S. universities to provide interprofessional leadership training through classroom, online, and service-oriented learning in 5 countries in Africa. This fellowship program prepares health professionals to design, implement, scale-up, evaluate, and lead health programs that are population-based and focused on prevention and HIV continues to challenge health systems, especially in low- and middle-income countries in Sub-Saharan Africa. A qualified workforce of transformational leaders is required to strengthen health systems and introduce policy reforms to address the barriers to HIV testing, treatment, and other HIV services. The 1-year Afya Bora Consortium Fellowship in Global Health capitalizes on academic partnerships between African and U.S. universities to provide interprofessional leadership training through classroom, online, and service-oriented learning in 5 countries in Africa. This fellowship program prepares health professionals to design, implement, scale-up, evaluate, and lead health programs that are population-based and focused on prevention and },

keywords = {},

pubstate = {published},

tppubtype = {article}

}