Marape

Vitamin D₃ Supplementation 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 7000IU 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) ≥32ng/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±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/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 7000IU/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±11ng/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

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.

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.

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/m2. Eighty-nine children had undetectable viral loads and the median CD4 count was 962 cells/mm3. 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.