Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

Background: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania.

Methods: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension.

Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial.

Aims/hypothesis: In sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA.

Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

Background: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.

Methods: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control).

Integrating HIV, diabetes and hypertension services in Africa: study protocol for a cluster randomised trial in Tanzania and Uganda.

Introduction: HIV programmes in sub-Saharan Africa are well funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Healthcare provision is organised from stand-alone clinics. In this cluster randomised trial, we are evaluating a concept of integrated care for people with HIV infection, diabetes or hypertension from a single point of care.

Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial.

Background: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana.

Methods: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018.

Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

Background: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.

Methods: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services.

Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana.

Background: Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations.

Methods: Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping.

Cross-sectional estimates revealed high HIV incidence in Botswana rural communities in the era of successful ART scale-up in 2013-2015.

Background: Botswana is close to reaching the UNAIDS "90-90-90" HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage.

Methods: We used a cross-sectional approach to assessing HIV incidence.

HIV Exposure and Formula Feeding Predict Under-2 Mortality in HIV-Uninfected Children, Botswana.

Objectives: To prospectively assess rates and detailed predictors of morbidity and mortality among HIV-exposed uninfected children and HIV-unexposed children in Botswana in a more recent era.

Study Design: We enrolled HIV-infected and HIV-uninfected mothers and their children in the prospective observational Tshipidi study at 2 sites (1 city and 1 village) in Botswana from May 2010-July 2012. Live-born children and their mothers were followed for 24 months postpartum.

Lack of Virological Suppression Among Young HIV-Positive Adults in Botswana.

Background: HIV-1 RNA load is the best biological predictor of HIV transmission and treatment response. The rate of virologic suppression among key subpopulations can guide HIV prevention programs.

Methods: The Botswana Combination Prevention Project performed a population-based household survey among adults in 30 communities in Botswana.

Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana.

Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV) or nevirapine (NVP) prophylaxis for the prevention of intrapartum mother-to-child HIV transmission (MTCT) among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants.

Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS) Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation), with a birth weight ≥ 2500 g and who were formula-fed from birth.

High HIV-1 RNA Among Newly Diagnosed People in Botswana.

HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to determine whether HIV-1 RNA level was associated with prior knowledge of HIV status among treatment-naive HIV-infected individuals in Botswana, a country with high rates of antiretroviral treatment (ART) coverage. This information may be helpful in targeting HIV diagnosis and treatment efforts in similar high HIV prevalence settings in a population-based survey.

The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana.

Background: Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH.

Methods: A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009.

Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV-exposed infants in a randomized controlled trial, Botswana.

Introduction: Despite declining risk of vertical HIV transmission, prophylactic cotrimoxazole (CTX) remains widely used to reduce morbidity and mortality in the event of HIV infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo-controlled trial of infant CTX prophylaxis, we sought to quantify emergence of antibiotic resistance.

Methods: HIV-exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX or placebo between 14 and 34 days of life and continued through 15 months.

Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial.

Background: Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear.

Methods: HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14-34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children.

Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana.

Introduction: A large and increasing number of HIV-infected women are conceiving on antiretroviral treatment (ART). While most antiretrovirals are considered safe in pregnancy, monitoring for rare pregnancy and infant adverse outcomes is warranted.

Methods: We conducted a retrospective secondary analysis nested within a clinical trial of infant cotrimoxazole vs.

Point-of-Care Cepheid Xpert HIV-1 Viral Load Test in Rural African Communities Is Feasible and Reliable.

Routine monitoring of HIV-1 RNA or viral load (VL) in patients on antiretroviral therapy (ART) is important, but there are multiple impediments to VL testing in resource-constrained settings. An accurate point-of-care (POC) HIV-1 VL test could alleviate many of these challenges. We compared the performance of the Cepheid Xpert HIV-1 VL assay against the laboratory-based Abbott m2000sp/m2000rt assay (Abbott assay).

Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey.

Background: HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90).

Methods: A population-based sample of individuals was recruited and interviewed in 30 rural and periurban communities from Oct 30, 2013, to Nov 24, 2015, as part of a large, ongoing community-randomised trial designed to assess the effect of a combination prevention package on HIV incidence.

Linear Growth Faltering Among HIV-Exposed Uninfected Children.

Background: HIV-exposed uninfected (HEU) children experience increased mortality compared with their HIV-unexposed uninfected (HUU) peers. It is unclear whether HEU children are also at increased risk for undernutrition, a modifiable risk factor for mortality.

Methods: We conducted a cross-sectional, population-based survey of children <5 years of age in 5 health districts in Botswana.

Recruitment, Follow-Up and Characteristics of HIV Infected Adults who Use Illicit Drugs in Southern Africa.

Background: With one of the worst HIV prevalence rates in the world, Botswana has made great strides in addressing AIDS. Nevertheless, to fully contain the epidemic, outreach to marginalized groups, including illicit drug users, is critical.

Objective: To conduct targeted outreach within an intervention trial to recruit HIV-infected drug users and assess HIV disease and nutritional status.

Phylodynamic analysis of HIV sub-epidemics in Mochudi, Botswana.

Southern Africa continues to be the epicenter of the HIV/AIDS epidemic. This HIV-1 subtype C epidemic has a predominantly heterosexual mode of virus transmission and high (>15%) HIV prevalence among adults. The epidemiological dynamics of the HIV-1C epidemic in southern Africa are still poorly understood.

Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering.

The goal of the study was to improve the methodology of HIV genotyping for analysis of HIV drug resistance and HIV clustering. Using the protocol of Gall et al. (A.

Estimated age and gender profile of individuals missed by a home-based HIV testing and counselling campaign in a Botswana community.

Introduction: It would be useful to understand which populations are not reached by home-based HIV-1 testing and counselling (HTC) to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission.

Methods: We present the results of a baseline home-based HTC (HBHTC) campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north-eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN) estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS-IV).

An augmented SMS intervention to improve access to antenatal CD4 testing and ART initiation in HIV-infected pregnant women: a cluster randomized trial.

Background: Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART.

Methods: We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana.