Phylodynamic Structure in the Botswana HIV Epidemic.

Background: Studying viral sequences can provide insights into the structure of host contact networks through which the virus is transmitted. Uncovering the population structure of the HIV-1 epidemic in Botswana will help optimise public health interventions and may identify hidden sub-epidemics. We sought to determine the phylodynamic structure of the Botswana HIV-1 epidemic from viral sequence genetic data.

Correction: Caregivers of children with HIV in Botswana prefer monthly IV Broadly Neutralizing Antibodies (bNAbs) to daily oral ART.

[This corrects the article DOI: 10.1371/journal.pone.

Caregivers of children with HIV in Botswana prefer monthly IV Broadly Neutralizing Antibodies (bNAbs) to daily oral ART.

Introduction: Monthly intravenous infusion of broadly neutralizing monoclonal antibodies may be an attractive alternative to daily oral antiretroviral treatment for children living with HIV. However, acceptability among caregivers remains unknown.

Methods: We evaluated monthly infusion of dual bNAbs (VRCO1LS and 10-1074) as a treatment alternative to ART among children participating in the Tatelo Study in Botswana.

Predicted resistance to broadly neutralizing antibodies (bnAbs) and associated HIV-1 envelope characteristics among seroconverting adults in Botswana.

We used HIV-1C sequences to predict (in silico) resistance to 33 known broadly neutralizing antibodies (bnAbs) and evaluate the different HIV-1 Env characteristics that may affect virus neutralization. We analyzed proviral sequences from adults with documented HIV-1 seroconversion (N = 140) in Botswana (2013-2018). HIV-1 env sequences were used to predict bnAb resistance using bNAb-ReP, to determine the number of potential N-linked glycosylation sites (PNGS) and evaluate Env variable region characteristics (VC).

Hepatitis B surface antigen loss in individuals with chronic hepatitis B virus and HIV-1 infections in Botswana.

Objectives: We sought to determine hepatitis B surface antigen (HBsAg) loss and its predictors among people with chronic hepatitis B (CHB) infections and HIV (PWH) in Botswana.

Methods: Archived plasma samples from a cohort of PWH in Botswana (2013-2018) with 3 yearly time-points were used. Samples were screened for HBsAg, immunoglobulin M HBV core antibodies (anti-HBc IgM) and HBV e-antigen (HBeAg) at all time points.

Prevalence and control of hypertension in a high HIV-prevalence setting, insights from a population based study in Botswana.

In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed.

Fostemsavir resistance-associated polymorphisms in HIV-1 subtype C in a large cohort of treatment-naïve and treatment-experienced individuals in Botswana.

Fostemsavir (FTR) is a newly licensed antiretroviral drug that has been shown to have activity against HIV-1. The mechanism of action of FTR is different from all currently available antiretrovirals (ARVs), and as such, it offers hope for HIV-1 suppression in those people with HIV (PWH) who harbor HIV-1 variants with drug resistance mutations to currently used ARVs. Using 6,030 HIV-1 sequences covering the HIV-1 envelope from PWH in Botswana who are antiretroviral therapy (ART) naïve as well as those who are failing ART, we explored the sequences for FTR resistance-associated polymorphisms.

High prevalence of hepatitis delta virus among people with hepatitis B virus and HIV coinfection in Botswana.

Background: Approximately 15-20 million people worldwide are infected with hepatitis delta virus (HDV), which is approximately 5 % of people with chronic hepatitis B virus (HBV). Sub-Saharan Africa has high HDV prevalence, leading to worse clinical outcomes among people who are HIV/HBV/HDV tri-infected. There are limited data on HDV prevalence among people with HIV (PWH) who are HBV-infected and uninfected in Botswana.

Predicted broadly neutralizing antibody (bnAb) resistance and associated envelope characteristics of adults with HIV-1 seroconversion in Botswana.

We used HIV-1C sequences to predict (in silico) resistance to 33 known broadly neutralizing antibodies (bNAbs) and evaluate the different HIV-1 env characteristics that may affect virus neutralization. We analyzed proviral sequences from adults with documented HIV-1 seroconversion (N=140) in Botswana (2013-2018). HIV-1 env sequences were used to predict bnAb resistance using bNAb-ReP, to determine the number of potential N-linked glycosylation sites (PNGS) and evaluate env variable region characteristics (VC).

Archived rilpivirine-associated resistance mutations among ART-naive and virologically suppressed people living with HIV-1 subtype C in Botswana: implications for cabotegravir/rilpivirine use.

Objectives: Pre-existing rilpivirine resistance-associated mutations (RVP-RAMs) have been found to predict HIV-1 virological failure in those switching to long-acting injectable cabotegravir/rilpivirine. We here evaluated the prevalence of archived RPV-RAMs in a cohort of people living with HIV (PWH).

Methods: We analysed near full-length HIV-1 pol sequences from proviral DNA for the presence of RPV-RAMs, which were defined according to the 2022 IAS-USA drug resistance mutation list and Stanford HIV drug resistance database.

Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana.

Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children ( = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART.

Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana.

It remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking into account the effect of antiretroviral treatment (ART) and virologic suppression. HIV-1 gp120 V3 loop sequences from 5602 participants were analyzed for viral tropism using three coreceptor use predicting algorithms/tools: Geno2pheno, HIV-1C Web Position-Specific Score Matrices (WebPSSM) and the 11/25 charge rule.

Brief Report: Long-Term Clinical, Immunologic, and Virologic Outcomes Among Early-Treated Children With HIV in Botswana: A Nonrandomized Controlled Clinical Trial.

Background: Early antiretroviral treatment (ART) improves outcomes in children, but few studies have comprehensively evaluated the impact of ART started from the first week of life.

Methods: Children diagnosed with HIV within 96 hours of life were enrolled into the Early Infant Treatment Study in Botswana and followed on ART for 96 weeks. Nevirapine, zidovudine, and lamivudine were initiated; nevirapine was switched to lopinavir/ritonavir between weeks 2-5 in accordance with gestational age.

High Prevalence of Hepatitis B Virus Infection Among People With HIV in Rural and Periurban Communities in Botswana.

Background: We aimed to determine the prevalence of hepatitis B virus (HBV) infection among people with human immunodeficiency virus (PWH) in rural and periurban communities in Botswana.

Methods: PWH from a previous population-based study, the Botswana Prevention Combination Project, which enrolled adults in 30 communities across Botswana (2013-2018), were screened for HBV surface antigen (HBsAg) and HBV core antibody (anti-HBc). HBsAg-positive (HBsAg) samples were further screened for HBV core immunoglobulin M antibodies (anti-HBc immunoglobulin M [IgM]) and HBV e antigen (HBeAg).

Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana.

Background: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data.

Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.

Objectives: There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP).

Methods: A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation.

Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project.

Background: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision referrals increased coverage and decreased incidence over ∼29 months of follow-up.

Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/Ya Tsie trial.

Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence.

Methods: To elucidate patterns of HIV spread in universal test-and-treat trials, we quantified the contribution of geographic-location, gender, age, and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana.

HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana.

Objectives: To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project.

Methods: A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL.

To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approach.

Background: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence.

Methods: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16.

Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana.

Objective: To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.

Design: The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs).

Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.

Introduction: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study.

Implementation of Universal HIV Testing and Treatment to Reduce HIV Incidence in Botswana: the Ya Tsie Study.

Purpose Of Review: Antiretroviral treatment (ART) can dramatically reduce the risk of HIV transmission, but the feasibility of scaling up HIV testing, linkage and treatment to very high population levels, and its impact on population HIV incidence, were unknown. We review key findings from a community-randomized trial in which we evaluated the impact of "universal test and treat" (UTT) on population HIV incidence in Botswana, a resource-constrained country with both high HIV prevalence and high ART coverage before study inception.

Recent Findings: We conducted a community-randomized trial (the "Ya Tsie" trial or Botswana Combination Prevention Project (BCPP)) in 30 villages in Botswana from 2013 to 2018, with the goal of determining whether a combination of prevention interventions-with a focus on universal HIV testing and treatment-would reduce population-level HIV incidence.