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). Ä25D 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.
