Addressing an HIV cure in LMIC.

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial.

Background: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV.

Dolutegravir or Darunavir in Combination with Zidovudine or Tenofovir to Treat HIV.

Background: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine.

Methods: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine.

The impact of viraemia on inflammatory biomarkers and CD4+ cell subpopulations in HIV-infected children in sub-Saharan Africa.

Objective: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa.

Design: Longitudinal cohort study.

Methods: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.

Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda.

Introduction: Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda.

Sex, HIV Status, and Measures of Cardiac Stress and Fibrosis in Uganda.

Background Biomarkers of myocardial stress and fibrosis are elevated in people living with HIV and are associated with cardiac dysfunction. It is unknown whether sex influences these markers of heart failure risk in sub-Saharan Africa, where HIV burden is high and where the vast majority of women with HIV live. Methods and Results Echocardiograms and 6 plasma biomarkers (suppression of tumorigenicity-2, growth differentiation factor 15, galectin 3, soluble fms-like tyrosine kinase-1, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and cystatin C) were obtained from 100 people living with HIV on antiretroviral therapy and 100 HIV-negative controls in Uganda.

Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study.

Background: HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes.

Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda.

Introduction: Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART.

Lipidome association with vascular disease and inflammation in HIV+ Ugandan children.

Objective: HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD). The relationships among the lipidome, immune activation, and subclinical vascular disease in children with perinatally acquired HIV (PHIV) have not been investigated.

Methods: Serum lipid composition, including 13 lipid classes constituting 850 different lipid species were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated PHIV and 20 age-matched and sex-matched HIV- Ugandan children.

Specialty career preferences among final year medical students at Makerere University College of health sciences, Uganda: a mixed methods study.

Background: Uganda has an imbalanced distribution of the health workforce, which may be influenced by the specialty career preferences of medical students. In spite of this, there is inadequate literature concerning the factors influencing specialty career preferences. We aimed to determine the specialty career preferences and the factors influencing the preferences among fifth year medical students in the School of Medicine, Makerere University College of Health Sciences (MakCHS).

Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings.

Background: Dolutegravir (DTG) is now recommended to all HIV infected adults, adolescents, and children of right age by WHO. The low cost of $75 per year for generic DTG-based combination, has allowed 3.9 million people living with HIV (PLWH) in low and middle-income countries (LMICs) access to DTG.

An audit of registered radiology equipment resources in Uganda.

Introduction: the third Sustainable Development Goal (SDG) relates to Universal Health Coverage (UHC) and provision of quality essential health services. The Government of Uganda has operationalized this through the National Health Policy which stresses the importance of availability of functioning medical equipment in health facilities. There have been efforts by the Ministry of Health and Atomic Energy Council in Uganda to compile an inventory of imaging equipment in the country, however, this information has not been widely published.

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing.

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development.

Latent Tuberculosis Infection and Subclinical Coronary Atherosclerosis in Peru and Uganda.

Background: Tuberculosis (TB) has been linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). We assessed whether latent TB infection (LTBI) is associated with subclinical coronary atherosclerosis in 2 TB-prevalent areas.

Methods: We analyzed cross-sectional data from studies conducted in Lima, Peru, and Kampala, Uganda.

Plasma Inflammatory Biomarkers Predict CD4+ T-cell Recovery and Viral Rebound in HIV-1 Infected Africans on Suppressive Antiretroviral Therapy.

This multicountry prospective study investigated whether persistent systemic inflammation, measured by 8 plasma biomarkers, in HIV-1-infected Africans during suppressive antiretroviral therapy (ART) (viral load <50 copies/mL), was associated with CD4+ T-cell recovery and viral rebound (>1000 copies/mL) during long-term treatment. On-ART sCD14 and C-reactive protein concentrations were inversely associated with subsequent CD4+ T-cell counts. Risk of viral rebound was increased for participants with higher on-ART CXCL10 concentrations and reduced for those with a greater sCD163 decline during the first year of ART.

New Insights on Long-Term Hepatitis B Virus Responses in HIV-Hepatitis B virus Co-infected Patients: Implications for Antiretroviral Management in Hepatitis B virus-Endemic Settings.

Background: WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting.

Monocyte activation in persons living with HIV and tuberculosis coinfection.

Objectives: To characterize monocyte subsets and activation in persons living with HIV (PLWH) with tuberculosis coinfection.

Design: Cross-sectional study within a cohort of PLWH and HIV-uninfected participants at the Joint Clinical Research Centre in Kampala, Uganda.

Methods: Participants were at least 45 years old with at least one cardiovascular risk factor.

Deep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1.

Exposure of the genital mucosa to a genetically diverse viral swarm from the donor HIV-1 can result in breakthrough and systemic infection by a single transmitted/founder (TF) virus in the recipient. The highly diverse HIV-1 envelope (Env) in this inoculating viral swarm may have a critical role in transmission and subsequent immune response. Thus, chronic (Env) and acute (Env) Env chimeric HIV-1 were tested using multivirus competition assays in human mucosal penile and cervical tissues.

The effect of TB treatment on health-related quality of life for people with advanced HIV.

Study A5274 was an open-label trial of people with HIV (PLHIV) with CD4 cell count <50 cells/µL who were randomized to empirical TB treatment vs. isoniazid preventive therapy (IPT) in addition to antiretroviral therapy (ART). We evaluated health-related quality of life (HRQoL) by study arm, changes over time, and association with sociodemographic and clinical factors.

A randomised feasibility trial of an intervention to support sharing of HIV status for 18-25-year olds living with perinatally acquired HIV compared with standard care: HIV Empowering Adults' Decisions to Share-UK/Uganda Project (HEADS-UP).

Background: Young adults with perinatally acquired HIV (PAH) face several challenges, including adhering to antiretroviral therapy (ART), managing the risk of onward HIV transmission and maintaining positive well-being. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges by facilitating emotional and practical support. Rates of HIV status sharing are, however, low in this population.

"Because we all have to grow up": supporting adolescents in Uganda to develop core competencies to transition towards managing their HIV more independently.

Introduction: Sustaining optimal adherence is the major challenge facing adolescents living with HIV (ALHIV), particularly in low-resource settings, where "second-line" is often the last accessible treatment option. We explored the knowledge and skills adolescents need in order to maintain improved adherence behaviours, and the specific ways clinicians and caregivers may support young people to do so more independently.

Methods: We conducted individual, in-depth interviews with 20 ALHIV aged 10 to 18 years in Uganda in 2017 to 2018.

Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda.

Background: Increasing first-line treatment failures in low- and middle-income countries (LMICs) have led to increased use of integrase strand transfer inhibitors (INSTIs) such as dolutegravir. However, HIV-1 susceptibility to INSTIs in LMICs, especially with previous raltegravir exposure, is poorly understood due to infrequent reporting of INSTI failures and testing for INSTI drug resistance mutations (DRMs).

Methods: A total of 51 non-subtype B HIV-1 infected patients failing third-line (raltegravir-based) therapy in Uganda were initially selected for the study.

Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.

Introduction: Management of concomitant use of ART and TB drugs is difficult because of the many drug-drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps.

Methods: We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines.