Association of Vitamin D Insufficiency and Protective Tenofovir Diphosphate Concentrations with Bone Toxicity in Adolescent Boys and Young Men using Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-Exposure Prophylaxis.

We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as <20ng/mL (insufficient/deficient) versus 20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700fmol/punch (protective against HIV acquisition) versus 700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD <20ng/mL (OR=5.4; 95% CI=1.9-16.5) and blacks (OR=4.9; 95% CI=1.7-15.2) had greater odds of bone toxicity than those with 25-OHD 20 or other races. TFV-DP was not associated with bone toxicity (OR=1.6; 95% CI=0.5-5.5). In multivariable analysis, compared with those with 25-OHD 20 and TFV-DP 700, those with 25-OHD 20 and TFV-DP >700 (OR=11.5; 95% CI=1.4-169.6), 25-OHD <20 and TFV-DP 700 (OR=19.4; 95% CI=3.0-228.7), and 25-OHD <20 and TFV-DP >700 (OR=32.3; 95% CI=3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.