Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents: Week 48 Safety, Efficacy, Virology and Pharmacokinetics.

Background: Rilpivirine 25 mg qd yields similar exposure in adolescents and adults (Pediatric study in Adolescents Investigating a New NNRTI TMC278 [PAINT] Cohort 1, Part 1). We report rilpivirine safety, efficacy, virology and pharmacokinetics in adolescents during 48 weeks of treatment (Cohort 1, Part 2).

Methods: PAINT (NCT00799864) is a phase II, ongoing, open-label, single-arm trial of rilpivirine plus 2 investigator-selected nucleoside/nucleotide reverse-transcriptase inhibitors.

A comparision of the yield of three tuberculosis screening modalities among people living with HIV: a retrospective quasi-experiemental study.

Background: The Intensified Case Finding (ICF) tool was approved for TB screening in 2011; however there is still paucity of robust data comparing yields of the different ICF screening modalities. We compared yields of three different screening modalities for TB among Patients Living with HIV (PLHIV) in Uganda in order to inform National TB Programs on the most effective TB screening method.

Methods: This was a retrospective quasi-experimental study conducted at an Out-Patient HIV/AIDS clinic in Uganda.

Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children.

Objectives: To characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children.

Methods: Non-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children aged 0.

Second-line HIV Treatment in Ugandan Children: Favorable Outcomes and No Protease Inhibitor Resistance.

Background: Data on pediatric second-line antiretroviral treatment (ART) outcomes are scarce, but essential to evaluate second-line and design third-line regimens.

Methods: Children ≤12 years switching to second-line ART containing a protease inhibitor (PI) in Uganda were followed for 24 months. Viral load (VL) was determined at switch to second-line and every 6 months thereafter; genotypic resistance testing was done if VL ≥ 1000 cps/ml.

Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study.

Background: Women are under-represented in HIV antiretroviral therapy (ART) studies. Guidelines for selection of ART as initial therapy in patients with HIV-1 infection do not contain sex-specific treatment. We aimed to assess the safety and efficacy of the single tablet integrase inhibitor regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate compared with a boosted protease inhibitor regimen of ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate.

The burden of maternal morbidity and mortality attributable to hypertensive disorders in pregnancy: a prospective cohort study from Uganda.

Background: Hypertensive disorders of pregnancy are a major cause of morbidity and mortality. The objective was to estimate the disease burden attributable to hypertensive disorders of pregnancy in two referral hospitals in Uganda.

Methods: Through a prospective cohort study conducted in Jinja and Mulago hospitals in Uganda from March 1, 2013 and February 28, 2014, hypertension-related cases were analyzed.

Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.

Background: As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce.

Methods: HIV-1-infected adults were included if they received >180 days of PI-based second-line ART.

International AIDS Society global scientific strategy: towards an HIV cure 2016.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure.

Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa.

Objectives: Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa.

Methods: HIV-1-positive adults and children on an NNRTI-based first-line ART were included.

Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy.

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.

Acceptability of lopinavir/r pellets (minitabs), tablets and syrups in HIV-infected children.

Background: Lopinavir/ritonavir 'pellets' were recently tentatively approved for licensing. We describe their acceptability for infants and children up to 48 weeks.

Methods: CHAPAS-2 was a randomized, two-period crossover trial comparing syrup and pellets in HIV-infected infants (n=19, group A, aged 3-<12 months) and children (n=26, group B, 1-<4 years) and tablets and pellets in older children (n=32, group C, 4-<13 years) from two clinics ('JCRC', 'PIDC') in Uganda.

Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.

Background: Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children.

Methods: We analyzed data from 128 African children (aged 1.

Role of Natural Autoantibodies in Ugandans With Rheumatic Heart Disease and HIV.

Background: Rheumatic heart disease (RHD) and HIV are prevalent diseases in sub-Saharan Africa, but little is known about their potential interrelationships. The objective of this study was to assess the prevalence of protective natural autoantibodies among patients with RHD in Uganda, and to determine whether the levels of these autoantibodies are affected by HIV status.

Methods: Participants were grouped according to RHD and HIV status.

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

Background: Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings.

Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy.

Background: There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.

Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure.

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure.

The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children.

Aims: Using a model-based approach, the efavirenz steady-state pharmacokinetics in African children is characterized, quantifying demographic and genotypic effects on the drug's disposition. Simulations are also conducted allowing prediction of optimized doses of efavirenz in this population.

Methods: We modelled the steady-state population pharmacokinetics of efavirenz in Ugandan and Zambian children using nonlinear mixed-effects modelling.

Maternal near misses from two referral hospitals in Uganda: a prospective cohort study on incidence, determinants and prognostic factors.

Background: Maternal near misses occur more often than maternal deaths and could enable more comprehensive analysis of risk factors, short-term outcomes and prognostic factors of complications during pregnancy and childbirth. The study determined the incidence, determinants and prognostic factors of severe maternal outcomes (near miss or maternal death) in two referral hospitals in Uganda.

Methods: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, where cases of severe pregnancy and childbirth complications were included.

HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda.

Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda.

Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011.

Using Exclusion-Based Sample Preparation (ESP) to Reduce Viral Load Assay Cost.

Viral load (VL) measurements are critical to the proper management of HIV in developing countries. However, access to VL assays is limited by the high cost and complexity of existing assays. While there is a need for low cost VL assays, performance must not be compromised.

Population level usage of health services, and HIV testing and care, prior to decentralization of antiretroviral therapy in Agago District in rural Northern Uganda.

Background: Decentralization of ART services scaled up significantly with the country wide roll out of option B plus in Uganda. Little work has been undertaken to examine population level access to HIV care particularly in hard to reach areas in rural Africa. Most work on ART scale up has been done at health facility level which omits people not accessing healthcare in the community.

Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial.

Objective: To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy.

Design: Randomized controlled trial was conducted in 5 sub-Saharan African countries.

Methods: Patients failing the first-line therapy according to WHO criteria after >12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2-3 clinician-selected nucleoside reverse transcriptase inhibitors, raltegravir, or as monotherapy after 12-week induction with raltegravir.

Cardiac Dysfunction Among Ugandan HIV-infected Children on Antiretroviral Therapy.

Background: Despite effective antiretroviral therapy (ART), HIV-infected children on treatment have been observed to have cardiac abnormalities. We sought to determine the prevalence, types and factors associated with cardiac abnormalities among HIV-infected Ugandan children on combination ART.

Methods: We carried out a cross-sectional study from July 2012 to January 2013, at Joint Clinical Research Centre among HIV-infected children aged 1-18 years.