Embracing uncertainty in early safety signals: A lesson from the Tsepamo study results describing neural tube defect risk and the use of Dolutegravir (DTG) in pregnancy.

Objective: We investigated how randomness may have contributed to the apparent decline in observed risk of neural tube defects (NTDs) following in utero dolutegravir (DTG) exposure. We aimed to describe statistical approaches to uncertainty using accessible language for non-statistical audiences.

Methods: We reanalyzed Tsepamo Study data using frequentist confidence intervals, repeated intervals accounting for group sequential monitoring, and Bayesian posterior and posterior predictive distributions.

Predictors of Concurrent Sexual Partnerships and Association with Recent HIV Infection in a Large Population-Based Survey in Botswana.

Background: Multiple concurrent sexual partnerships (MCP) may drive new HIV infections. We investigated the association between MCP and recent or incident HIV infection in a cluster-randomized HIV prevention trial that followed a population-based HIV incidence cohort across 30 communities in Botswana.

Methods: We used structured questionnaires to evaluate MCP over prior 12 months, defined as either (i) MCP per UNAIDS definition or (ii) concurrent sexual relationship per survey questions.

Target trials of pre-conception switch from Nevirapine- or Efavirenz-based ART to dolutegravir-based ART on adverse birth and maternal outcomes.

Objective: To compare the effect of pre-conception switching from nevirapine (NVP) and efavirenz (EFV) to dolutegravir (DTG) based ART on adverse birth and maternal outcomes.

Design: Two target trial emulations using the Tsepamo Birth Outcomes Surveillance Study in Botswana.

Methods: Among individuals who initiated NVP or EFV, we compared those who switched to DTG with those who did not switch prior to pregnancy.

The association between systemic inflammation and albuminuria among people living with HIV: A cross-sectional study from Botswana.

Treated human immunodeficiency virus (HIV) is associated with persistent systemic inflammation, even after many years of sustained viral suppression following initiation of antiretroviral therapy (ART). Albuminuria is common among people living with HIV (PLWH), but the impact of persistent systemic inflammation on outcome of albuminuria is not well understood. Thawed serum samples from PLWH who participated in an albuminuria prevalence study in Gaborone, Botswana, between January 2020 and March 2022, were selected randomly for a cross-sectional study of the link between inflammation and albuminuria.

Comparison of central obesity prevalence among adults living with and without HIV in Botswana: a cross-sectional study.

Objectives: The aim was to establish the community prevalence of central obesity in Botswana and assess its association with HIV status.

Design: We performed a one-time central obesity assessment nested within a community-based cluster-randomised controlled HIV treatment and prevention trial (Botswana Combination Prevention Project (BCPP)) conducted in Botswana.

Setting: The BCPP enrolled consenting adults from a random sample of 20% of households in 30 rural/peri-urban communities.

Predictive markers for sustained viral suppression on dual bNAbs during ART interruption in children.

Background: Simple clinical markers may predict favorable outcomes in pediatric HIV treatment and cure trials. We report findings for biomarker combinations evaluated during the broadly neutralizing antibodies (bNAbs)-only step of the Tatelo Study in Botswana.

Methods: Twenty-five children who were on ART since birth received up to 24 weeks of bNAb-only treatment (VRC01LS+10-1074).

Prospective longitudinal assessment of Albumin-to-Creatinine ratio (ACR) in a clinical cohort of people living with HIV in Gaborone, Botswana.

Background: People living with HIV (PLWH) in sub-Saharan Africa are vulnerable to end organ dysfunction such as albuminuria, which is associated with an increased risk of cardiovascular and renal events. However, the prevalence of persistent albuminuria among PLWH in Africa is unclear. This observational prospective study assessed for persistence of albuminuria in a cohort of PLWH on longterm antiretroviral therapy (ART) across various HIV service platforms in Gaborone, Botswana.

Bone Mineral Content, Growth, and Renal Health of Infants With Perinatal Exposure to Maternal Dolutegravir Versus Efavirenz and Tenofovir Disoproxil Fumarate Versus Tenofovir Alafenamide: The Randomized IMPAACT 2010 (VESTED) Trial.

Background: The impact on infant bone, growth, and renal health of in utero and breast milk exposure to contemporary antiretroviral treatment (ART) remains unclear.

Methods: Six hundred forty-three pregnant women with HIV in 9 countries in Africa, Asia, and the Americas were randomized to start ART with dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG + FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF between 14 and 28 weeks' gestation and continued for 50 weeks postpartum. Pairwise comparisons used 2-sample t tests of mean week 26 infant bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry in a subset; mean infant z-scores for length-for-age z-score (LAZ), weight-for-age z-score (WAZ), and weight-for-length (WLZ) at 26 and 50 weeks; and mean infant creatinine and estimated creatinine clearance at birth and 26 weeks.

Neurodevelopmental outcomes in children exposed in utero to dolutegravir- or efavirenz-based antiretroviral treatment.

Objective: To examine the impact of in-utero exposure to dolutegravir (DTG)-based or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental outcomes.

Design: Prospective cohort design, enrolling three cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based three-drug ART during pregnancy, and children born to mothers without HIV (CHUU).

Methods: Primary child neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders.

High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana.

Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).

Subsequent pregnancies in the IMPAACT 2010/VESTED Trial: high rate of adverse outcomes in women living with HIV.

Introduction: Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment(ART), and timing of ART may impact risk.

Methods: In IMPAACT 2010 (VESTED), 643 pregnant WHIV in 9 countries were randomized 1:1:1 to initiate ART: dolutegravir (DTG)+emtricitabine(FTC)/tenofovir alafenamide(TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (<20 weeks), stillbirth (≥20 weeks), preterm delivery (<37 weeks) and small-for-gestational-age (SGA).

Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana.

Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.

Access to and Utilization of Endocrine Therapy Among Breast Cancer Survivors in Botswana.

Purpose: Breast cancer (BC) is the most common female cancer worldwide, and the burden is increasing across sub-Saharan Africa. For women with hormone receptor-positive (HR+) cancers, endocrine therapy (ET) taken for 5-10 years can reduce the risk of recurrence by half. We explored experiences with ET and barriers to utilization among survivors in Botswana.

A qualitative assessment of barriers to iron and folic acid supplementation among pregnant women in Botswana.

Background: Antenatal iron and folic acid (IFA) supplementation remains an effective strategy in the prevention of maternal anemia and low birthweight and is universally recommended by WHO. However, uptake of IFA has varied globally due to challenges with acceptability, supply and distribution, counselling and knowledge, and access to health services. In Botswana, nearly one-third of pregnant women engaged in antenatal care do not receive IFA, despite it being standard of care.

Hepatitis Delta Virus Clade 8 Is the Predominant Clade Circulating in Botswana amongst People Living with HIV.

Hepatitis delta virus (HDV) co-infections more often result in severe hepatitis compared to hepatitis B virus (HBV) infections alone. Despite a high HDV prevalence (7.1%), information regarding circulating HDV clades is very limited in Botswana.

No impact of COVID-19 at delivery on maternal mortality or infant adverse birth outcomes in Botswana during the Omicron era.

SARS-CoV-2 infection during pregnancy was associated with maternal mortality and adverse birth outcomes in the pre-Omicron era, including a stillbirth rate of 5.6% in Botswana. We re-evaluated these outcomes in the Tsepamo Study during the Omicron era.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Background: Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

Methods: A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only.

Lipid and Glucose Profiles in Pregnant Women With HIV on Tenofovir-based Antiretroviral Therapy.

Background: Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy are limited. We evaluated metabolic markers in pregnant women with human immunodeficiency virus (HIV) after starting TAF- versus TDF-based ART.

Methods: We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC + DTG; n = 217) or TDF/FTC + DTG (n = 215).

Molecular Characterization of Hepatitis B Virus in People Living with HIV in Rural and Peri-Urban Communities in Botswana.

(1) Background: Hepatitis B virus (HBV) sequencing data are important for monitoring HBV evolution. We aimed to molecularly characterize HBV sequences from participants with HBV surface antigen-positive (HBsAg+) serology and occult hepatitis B infection (OBI+). (2) Methods: We utilized archived plasma samples from people living with human immunodeficiency virus (PLWH) in Botswana.

Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana.

Background: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19).

Methods: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023.

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.