Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV.

Introduction: Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda.

Methods: A prospective observational cohort study was performed in 2017-2021 in Uganda.

Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver-child dyads' perspective.

Background: Worldwide, 1.7 million children younger than 15 years were living with HIV in 2021. Only 52% of them had access to antiretrovirals (ARVs).

Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial.

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis.

Determinants of testing for HIV among young people in Uganda. A nested, explanatory-sequential study.

Awareness of HIV serostatus helps individuals calibrate behaviour or link to care. Globally, young people (15-24years) contribute over 30% of new HIV infections. Despite progress in enhancing access to HIV services, HIV testing among young people in Uganda is below target.

The hard part we often forget: providing care to children and adolescents with advanced HIV disease.

Introduction: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized.

Discussion: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence.

Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group.

Background: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

Methods: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio.

Sex modulates the association between inflammation and coronary atherosclerosis among older Ugandan adults with and without HIV.

Objective: Inflammation is key in the pathogenesis of atherosclerotic coronary artery disease (CAD). Distinct sex-specific inflammatory mechanisms may contribute to CAD in sub-Saharan Africa (SSA), where environmental and biological determinants of systemic inflammation may differ from those in high-income settings.

Approach And Results: We investigated sex differences in inflammatory markers and CAD in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV.

Impact of sub-optimal HIV viral control on activated T cells.

Objective: HIV viral load (VL) monitoring is generally conducted 6-12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation.

Design: Two hundred and eight participants starting protease inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38 + /HLA-DR + immunophenotyping performed (CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomization.

Differential expression of host protein biomarkers among symptomatic clinic attendees finally diagnosed with tuberculosis and other respiratory diseases with or without latent Mycobacterium tuberculosis infection.

Background: There is a need for new tools for the diagnosis of tuberculosis (TB) amongst patients who present at primary health care centers with symptoms suggestive of TB.

Objectives: To assess the abilities of selected blood-based host biomarkers to discriminate between patients who self-presented with symptoms suggestive of TB and were subsequently diagnosed with pulmonary tuberculosis (PTB), other respiratory diseases (ORD) with latent Mycobacterium tuberculosis infection (ORD_LTBI) or ORD without latent infection (ORD_NoLTBI).

Methods: Presumptive TB patients (n = 161) were enrolled at a TB Clinic in Kampala, Uganda, and blood was collected.

Barriers to Uptake of Long-Acting Antiretroviral Products for Treatment and Prevention of HIV in Low- and Middle-Income Countries (LMICs).

Long-acting injectable antiretroviral therapy (LA ART) has been found to be non-inferior to daily oral ART in phase 3 clinical trials and is poised to soon enter routine clinical care. This treatment modality has the potential to address many barriers to daily oral ART adherence among people living with human immunodeficiency virus (HIV) and for HIV Pre-Exposure prevention. Data from the Patient Reported Outcomes (PROs) showed high rates of satisfaction, acceptability, tolerability and preference for the LA regimen, compared with the daily oral treatment.

Thinness among children aged 5-17 years living in Nakivale refugee settlement, South Western Uganda: a cross-sectional study.

Background: Hunger and malnutrition are rampant among refugees and displaced populations, many of whom are infants and children. We sought to determine the prevalence and factors associated with thinness among children aged 5-17 years living in Nakivale refugee settlement, Isingiro district, southwestern Uganda.

Methods: This was a cross sectional study that enrolled 420 children aged 5 to 17 years.

A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates.

Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.

New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?

Combined HIV antiretroviral therapy (cART) has been effective except if drug resistance emerges. As cART has been rolled out in low-income countries, drug resistance has emerged at higher rates than observed in high income countries due to factors including initial use of these less tolerated cART regimens, intermittent disruptions in drug supply, and insufficient treatment monitoring. These socioeconomic factors impacting drug resistance are compounded by viral mechanistic differences by divergent HIV-1 non-B subtypes compared to HIV-1 subtype B that largely infects the high-income countries (just 10% of 37 million infected).

Global Antimicrobial Resistance and Use Surveillance System on the African continent: Early implementation 2017-2019.

Background: Antimicrobial resistance (AMR) is becoming a critical public health issue globally. The World Health Organization launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) to support the strengthening of the AMR evidence base.

Objective: The article describes the evolution of national AMR surveillance systems and AMR data reporting of countries in the African continent between 2017 and 2019, and the constraints, perceived impact and value of the participation in GLASS.

Design, development, and testing of a voice-text mobile health application to support Tuberculosis medication adherence in Uganda.

Background: Tuberculosis (TB) continues to persist with a high disease burden globally. Non-adherence to treatment remains a major problem to TB control. In Uganda, one in every four TB patients does not adhere to their TB medication.

Sex-specific performance of the ASCVD pooled cohort equation risk calculator as a correlate of coronary artery calcium in Kampala, Uganda.

Introduction: The prevalence of cardiovascular disease (CVD) is rising in Sub-Saharan Africa, but it is not known whether current risk assessment tools predict coronary atherosclerosis in the region. Furthermore, sex-specific performance and interaction with HIV serostatus has not been well studied.

Methods: This cross-sectional study compared ASCVD risk scores and detectable coronary artery calcium (CAC>0) by sex in Kampala, Uganda (n = 200).

Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial.

Background: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg.

Methods: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and <14 kg).

Longitudinal Changes in Subclinical Vascular Disease in Ugandan Youth With Human Immunodeficiency Virus.

Background: Prospective investigations on the risk of cardiovascular disease among youth with perinatally acquired human immunodeficiency virus (PHIV) in sub-Saharan Africa are lacking.

Methods: A prospective observational cohort study was performed in 101 youth (aged 10-18 years) with PHIV and 97 who were human immunodeficiency virus (HIV) uninfected (HIV-), from 2017 to 2021 at the Joint Clinical Research Center in Uganda. Participants with PHIV were receiving antiretroviral therapy (ART) and had HIV-1 RNA levels ≤400 copies/mL.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

Background: People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.

Methods: We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT ( = 426) or empiric 4-drug TB treatment ( = 424).

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial.

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB.

Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe.