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.

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.

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).

HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads.

Purpose: Monitoring HIV-1 drug resistance mutations (DRM) in treated patients on combination antiretroviral therapy (cART) with a detectable HIV-1 viral load (VL) is important for the selection of appropriate cART. Currently, there is limited data on HIV DRM at low-level viremia (LLV) (VL 401-999 copies/mL) due to the use of a threshold of VL ≥1000 copies/mL for HIV DRM testing. We here assess the performance of an in-house HIV drug resistance genotyping assay using plasma for the detection of DRM at LLV.

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.

The role of CYP2B6 516G>T polymorphism on efavirenz/nevirapine toxicity. Implications on treatment outcomes: Lessons from Botswana.

The two non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP), are currently the core antiretroviral drugs for treatment of HIV in sub-Saharan Africa including Botswana. The drugs are metabolized by Cytochrome P450 2B6 (CYP2B6) liver enzyme. The CYP2B6 gene that encodes for metabolism of these drugs is known to be highly polymorphic.

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.

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.

Human Immunodeficiency Virus (HIV) Genetic Diversity Informs Stage of HIV-1 Infection Among Patients Receiving Antiretroviral Therapy in Botswana.

Background: Human immunodeficiency virus (HIV)-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However, the effect of antiretroviral treatment (ART) on the inference remains unknown.

Methods: Participants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n = 1944).

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana.

HIV-1 drug resistance poses a major threat to the success of antiretroviral therapy. The high costs of available HIV drug resistance assays prohibit their routine usage in resource-limited settings. Pan-degenerate amplification and adaptation (PANDAA), a focused genotyping approach based on quantitative PCR (qPCR), promises a fast and cost-effective way to detect HIV drug resistance mutations (HIVDRMs).

Association of Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana.

Purpose: CYP2B6 liver enzyme metabolizes the two non-nucleoside reverse transcriptase inhibitors Efavirenz (EFV) and Nevirapine (NVP) used in the antiretroviral therapy (ART) regimens for HIV-infected individuals. Polymorphisms of the gene influence drug levels in plasma and possibly virological outcomes. The aim of this study was to explore the potential impact of genotype and haplotype variation on the risk of developing EFV/NVP drug resistance mutations (DRMs) in HIV-1 patients receiving EFV-/NVP-containing regimens in Botswana.

Incidence of hepatitis B virus infection among human immunodeficiency virus-infected treatment naïve adults in Botswana.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is highest in sub-Saharan Africa and results in accelerated clinical outcomes compared with HBV or HIV mono-infection. HBV clearance rates are higher in healthy adults; however, in sub-Saharan Africa, there are limited data on clearance of incident HBV in HIV-infected adults. Therefore, we sought to estimate HBV incidence and HBV surface antigen (HBsAg) clearance in HIV-infected adults in Botswana.

High incidence of tuberculosis in the first year of antiretroviral therapy in the Botswana National antiretroviral therapy programme between 2011 and 2015.

Objective: Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana.

Design: A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program.

Molecular characterization of hepatitis C virus in liver disease patients in Botswana: a retrospective cross-sectional study.

Background: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin.

Self-reported risky sexual practices among adolescents and young adults in Botswana.

Background: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming.

Objectives: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities.

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.

Molecular characterization of hepatitis B virus in blood donors in Botswana.

Hepatitis B virus (HBV) poses a significant threat to blood transfusion safety in sub-Saharan Africa (SSA) where allogeneic blood donations are screened serologically, and more sensitive nucleic acid tests (NATs) are utilized infrequently. HBV strains circulating among blood donors in Botswana are not yet characterized. We designed a cross-sectional study to determine the HBV sub-genotypes and prevalence of hepatitis B surface antigen (HBsAg) among blood donors between November 2014 and October 2015.

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.

Molecular Characterization of Near Full-Length Genomes of Hepatitis B Virus Isolated from Predominantly HIV Infected Individuals in Botswana.

The World Health Organization plans to eliminate hepatitis B and C Infections by 2030. Therefore, there is a need to study and understand hepatitis B virus (HBV) epidemiology and viral evolution further, including evaluating occult (HBsAg-negative) HBV infection (OBI), given that such infections are frequently undiagnosed and rarely treated. We aimed to molecularly characterize HBV genomes from 108 individuals co-infected with human immunodeficiency virus (HIV) and chronic hepatitis B (CHB) or OBI identified from previous HIV studies conducted in Botswana from 2009 to 2012.

In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm.

Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino acid (aa) variants on HBV protein function, are necessary.

Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study.

Background: Global rollout of dolutegravir-based antiretroviral therapy (ART) has been hampered in part by insufficient safety data in pregnancy. We compared birth outcomes among women initiating dolutegravir-based ART with those among women initiating efavirenz-based ART in pregnancy in Botswana.

Methods: In this observational study, we captured birth outcome data at eight government hospitals throughout Botswana (~45% of all deliveries in the country) in an ongoing study that started on Aug 15, 2014.

Correction: Immunological non-response and low hemoglobin levels are predictors of incident tuberculosis among HIV-infected individuals on Truvada-based therapy in Botswana.

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

Chronic and Occult Hepatitis B Virus Infection in Pregnant Women in Botswana.

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women in Botswana. Samples from 752 pregnant women were tested for hepatitis B surface antigen (HBsAg), and HBsAg-positive samples were tested for hepatitis B e antigen (HBeAg) and HBV DNA load.