Association between HIV/AIDS knowledge and stigma towards people living with HIV/AIDS in Botswana.

In Botswana, an estimated 350 000 people live with HIV/AIDS. HIV/AIDS testing rates are low, suggesting that many other people remain undiagnosed. Stigma related to HIV/AIDS is prevalent and contributes to low testing rates and under-diagnosis of the virus. Identifying factors that contribute to stigma, such as insufficient or inaccurate knowledge of HIV/AIDS, may be critical in increasing early identification and treatment. This cross-sectional study used nationally representative data from the 2013 Botswana AIDS Impact Survey (BAIS) IV to examine the relationship between HIV/AIDS knowledge and stigmatising attitudes toward people living with HIV/AIDS (PLWHA). The mean (standard error) for stigma towards PLWHA score and HIV/AIDS knowledge score were 0.99 (0.02) and 5.90 (0.03) respectively. HIV/AIDS knowledge score and stigma towards PLWHA score were strongly positively correlated r (4,4045) = 0.415, p < 0.001). After adjusting for potential confounders, HIV/AIDS knowledge score significantly predicted stigma towards PLWHA score [coefficient ß (95% CI)] [-0.25 (-0.29, -0.20), p < 0.001]. These findings imply that programmes and interventions that increase HIV/AIDS knowledge may reduce the pervasive apprehension, blame, and stigmatising attitude held towards PLWHA in Botswana.

Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana.

Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa. We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana-a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%-25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p = 2.2 × 10-16) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (<1%) pathogenic and damaging variants. Batswana clustered with other Southern African populations, but distinctly from 1000 Genomes African populations, and had limited evidence for admixture with extra-continental ancestries. We also observed a surprising lack of genetic substructure in Botswana, despite multiple tribal ethnicities and language groups, alongside a higher degree of relatedness than purported founder populations from the 1000 Genomes project. Our observations reveal a complex, but distinct, ancestral history and genomic architecture among Batswana and suggest that disease mapping within similar Southern African populations will require a deeper repository of genetic variation and allelic dependencies than presently exists.

Vitamin D3supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial.

OBJECTIVES: Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D3) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D). DESIGN: Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0-50.9 years. METHODS: Sixty subjects randomized within five age groups to either 4000 or 7000 IU per day of D3 and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32 ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores. RESULTS: Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log10 range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9 ng/ml to 56±18 ng/ml (p<0.0001) and 68% and 90% had 25D ≥32 ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000 IU/d group (p<0.04). Younger (5-13y) and older (30-50y) subjects had greater Δ25D than those 14-29y (26±17 and 28±12 vs. 11±11 ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03). CONCLUSIONS: In a pilot study in Botswana, 12-week high dose D3 supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers. TRIAL REGISTRATION: ClinicalTrials.gov NCT02189902.

Performance of the QuantiFERON-TB gold interferon gamma release assay among HIV-infected children in Botswana.

Interferon gamma release assays (IGRAs) are poorly studied in HIV-infected children. The authors prospectively evaluated QuantiFERON-TB Gold results and family-described tuberculosis (TB) risk factors in 100 HIV-infected children in Botswana. Median age was 10.2 years; 58 were girls, 92 had received the Bacillus Calmette-Guérin (BCG) vaccine, 98 were receiving antiretroviral therapy, and the median body mass index was 15.8 kg/m(2). Eighty-nine children had undetectable viral loads and the median CD4 count was 962 cells/mm(3). Eighteen children had been treated for TB in the last 3 years. In the last 3 years, 36 (including 9 with TB) had contact with persons with TB (26 within/15 outside the home and 5 had >1 contact). In all, 96 children had negative IGRAs, 3 were indeterminate, and 1 was positive. The positive IGRA was reported in a child treated for TB prior to 3 years. Interferon γ release assay positivity was rare in this pediatric cohort living in an area with a high prevalence of TB.

Protease genotypes in patients failing protease inhibitor-based antiretroviral therapy at a pediatric center in Botswana.

With increasing use of protease inhibitors (PI) in Botswana, a large proportion of HIV-infected children are now exposed to PI-based regimens. There is limited protease genotype data from African children and adolescents who have failed PI-based antiretroviral therapy. We describe a cohort of pediatric HIV-infected patients experiencing virologic failure at time of second-line or salvage PI-based regimens and analyze associated PI mutations.

Early outcomes of darunavir- and/or raltegravir-based antiretroviral therapy in children with multidrug-resistant HIV at a pediatric center in Botswana.

BACKGROUND: Data on the use of ritonavir-boosted darunavir (DRV/r) and/or raltegravir (RAL) in resource-limited settings are rare and there is currently no published data regarding their use among African children. Botswana has recently made DRV/r and RAL available for patients failing second-line antiretroviral therapy (ART). METHODS: Retrospective chart review of 4 multidrug-resistant pediatric patients on DRV/r- and/or RAL-based regimens. Viral load, CD4 count, adherence by pill count, and World Health Organization (WHO) clinical stage prior to and after switch to DRV/r- and/or RAL-based regimen were assessed. Antiretroviral therapy history, duration of virologic failure, and time to viral suppression were also noted. Genotypic resistance assays reviewed for mutations present prior to switch. RESULTS: All patients achieved viral suppression, showed improved/stable CD4 counts, and obtained or maintained WHO clinical treatment stage I, even after long-standing virologic/immunologic failure. CONCLUSIONS: Well tolerated by and effective in our patients, DRV/r and RAL provide potentially lifesaving ART options for children and adolescents in resource-limited settings failing ART due to ritonavir-boosted lopinavir (LPV/r) resistance.