Feasibility of vitamin D supplementation interventions to mitigate HIV pre-exposure prophylaxis-related bone mineral density loss: a cross-sectional survey

Shaoyuan Wang,1 Jean-Luc Kortenaar,1,2 Mark W Hull,3 Gordon Arbess,4 James RM Owen,4 Darrell HS Tan1,5,6 1Division of Infectious Diseases, St Michael’s Hospital, Toronto, ON, Canada; 2Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 3Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 4Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, ON, Canada; 5Centre for Urban Health Solutions, St. Michael’s Hospital, Toronto, ON, Canada; 6Division of Infectious Diseases, University of Toronto, Toronto, ON, Canada Background: Daily tenofovir disoproxil fumarate (TDF)/emtricitabine as HIV pre-exposure prophylaxis (PrEP) causes subclinical decreases in bone mineral density (BMD). We surveyed PrEP users to assess feasibility for a clinical trial of vitamin D supplementation to mitigate TDF-induced BMD loss. Methods: We recruited participants using or starting PrEP in Toronto and Vancouver. The primary objective was to assess the acceptability of daily or weekly vitamin D supplementation. We also assessed the acceptability of calcium supplementation, existing use of non-pharmacological bone health interventions, prevalence of osteoporosis risk factors, and bone health knowledge (Osteoporosis Knowledge Test, OKT). Results: Of 161 participants, 72.1% were current PrEP users, 18.0% were starting PrEP, and 9.9% did not indicate their PrEP status. All identified as males, 88.8% as gays, and 67.1% as Whites. Median (IQR) age was 32.0 (29.0, 40.0) years, and 62.1% reported family income ≥$60,000/year. Among those not already using the interventions, willingness to supplement with daily vitamin D, weekly vitamin D, or daily calcium was very high at 90.9%, 96.4%, and 93.0 %, respectively. Only 31.0% reported adequate dietary calcium intake, while 42.9% reported ≥1 osteoporosis risk factor (most commonly, alcohol and smoking). Overall bone health knowledge was low, as median (IQR) OKT score was 16/32. In post hoc comparisons, current PrEP users may have been more likely than new PrEP users to engage in bone loading exercise (Bone-specific Physical Activity Questionnaire score=12.5 vs 3.6, P=0.001) and have greater bone health knowledge (OKT=17 vs 14, P=0.08), but they had similar levels of current vitamin D supplementation (37.4% vs 21.4%, P=0.11), calcium supplementation (11.2% vs 13.8%, P=0.70), and adequate dietary calcium intake (32.7% vs 25.0%, P=0.43). Discussion: The high acceptability of vitamin D and calcium supplementation in this cohort suggests that enrollment into a clinical trial of such interventions to mitigate PrEP-induced BMD loss is feasible. Keywords: HIV, pre-exposure prophylaxis, vitamin D, calcium, bone and bones, bone densit

A randomized control trial of an Ultra-Short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe

OBJECTIVE To assess the practicality and effectiveness of an Ultra-Short zidovudine regimen for prevention of perinatal HIV transmission in rural Zimbabwe. DESIGN Double-blinded placebo-controlled randomized clinical trial. SETTING The Salvation Army Howard Hospital, a district hospital in rural Zimbabwe. SUBJECTS 222 HIV positive pregnant women presenting for antenatal care prior to 36 weeks were randomized. Twenty nine women were lost to follow up. INTERVENTION In the Thai regimen, mothers received zidovudine (300 mg po bid) from 36 weeks gestation until labour, and zidovudine (300 mg po q3h) during labour, and the neonates received a placebo. In the Ultra-Short regimen, the mothers received a placebo from 36 weeks to labour, then zidovudine (300 mg po q3h) in labour. The neonates received zidovudine (2 mg/kg po qid) for the first three days of life. MAIN OUTCOME MEASURE Infant HIV RNA status at six weeks of life. RESULTS Results were available for 90 infants from the Thai group and 89 infants from the Ultra-Short group. Infant HIV seroconversion rates at six weeks of life were 18.9% (95%CI 10.8 to 27.0) with the Thai regimen, and 15.7% [95% Confidence Interval (CI) 8.1 to 23.4] with the Ultra-Short regimen. The upper bound of seroconversion in the Ultra-Short group was lower than the 25% seroconversion boundary that was specified to show equivalence. CONCLUSIONS Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen, it also has many practical advantages. Ultra-Short is thus a preferable protocol