Havens Peter L, Tamhane Ashutosh, Stephensen Charles B, Schuster Gertrud U, Gordon Catherine M, Liu Nancy, Wilson Craig M, Hosek Sybil G, Anderson Peter L, Kapogiannis Bill G, Mulligan Kathleen
1 Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
2 Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama.
AIDS Res Hum Retroviruses. 2019 Feb;35(2):123-128. doi: 10.1089/AID.2018.0096. Epub 2018 Nov 5.
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 <20 ng/mL (insufficient/deficient) versus ≥20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700 fmol/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 <20 ng/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.
我们研究了25-羟基维生素D（25-OHD）、替诺福韦酯（TDF）与骨毒性之间的关联。我们对男男性行为者（YMSM）中的TDF/恩曲他滨（FTC）暴露前预防（PrEP）进行了研究。骨毒性通过从基线到第48周的骨矿物质密度/含量变化来预先定义。基线血清25-OHD分为<20 ng/mL（不足/缺乏）与≥20 ng/mL（充足），第48周干血斑中的替诺福韦二磷酸（TFV-DP）分为>700 fmol/打孔（预防HIV感染）与≤700 fmol/打孔。通过单变量和多变量逻辑回归分析关联，报告粗比值比和调整后的比值比（OR）以及95%置信区间（CI）。在101名入组者中，69人进行了完整的骨评估和25-OHD检测；其中59人有第48周的TFV-DP数据。中位（Q1-Q3）年龄为20（18-21）岁；54%为黑人/非裔美国人。在单变量分析中，基线25-OHD<20 ng/mL的参与者（OR = 5.4；95% CI = 1.9-16.5）和黑人（OR = 4.9；95% CI = 1.7-15.2）发生骨毒性的几率高于25-OHD≥20 ng/mL的参与者或其他种族。TFV-DP与骨毒性无关（OR = 1.6；95% CI = 0.5-5.5）。在多变量分析中，与25-OHD≥20且TFV-DP≤700的参与者相比，25-OHD≥20且TFV-DP>700（OR = 11.5；95% CI = 1.4-169.6）、25-OHD<20且TFV-DP≤700（OR = 19.4；95% CI = 3.0-228.7）以及25-OHD<20且TFV-DP>700（OR = 32.3；95% CI = 3.3-
