Havens Peter L, Stephensen Charles B, Van Loan Marta D, Schuster Gertrud U, Woodhouse Leslie R, Flynn Patricia M, Gordon Catherine M, Pan Cynthia G, Rutledge Brandy, Liu Nancy, Wilson Craig M, Hazra Rohan, Hosek Sybil G, Anderson Peter L, Seifert Sharon M, Kapogiannis Bill G, Mulligan Kathleen
Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee;
US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, and.
Clin Infect Dis. 2017 Feb 1;64(3):317-325. doi: 10.1093/cid/ciw765. Epub 2016 Nov 15.
We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity.
In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups.
There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables.
These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group.
NCT01769469.
我们旨在确定替诺福韦酯（TDF）相关骨毒性中肾脏和内分泌变化的相对重要性。
在一项针对未感染人类免疫缺陷病毒（HIV）的男男性行为年轻男性进行的每日TDF/恩曲他滨（FTC）暴露前预防（PrEP）研究中，我们测量了甲状旁腺激素（PTH）-维生素D-成纤维细胞生长因子23（FGF23）轴的血液和尿液标志物、肌酐以及肾小管对磷的重吸收（TRP）相对于基线的变化。我们探讨了这些变量与骨矿物质密度（BMD）变化之间的关系。使用红细胞中的替诺福韦二磷酸（TFV-DP）将参与者分为高药物暴露组和低药物暴露组。
共有101名参与者，中位年龄20岁（范围15至22岁）。与低药物暴露相比，高暴露参与者在研究第4周时PTH较基线升高，FGF23下降，肌酐、磷酸盐或TRP无差异。在48周时，高暴露组全髋关节BMD的中位（四分位间距）下降百分比高于低暴露组（分别为-1.59 [2.77]% 对 +1.54 [3.34]%；P = 0.001）；在高暴露参与者中，这与第4周的TFV-DP（呈负相关；r = -0.60，P = 0.002）和FGF23（呈正相关；r = 0.42；P = 0.039）相关，但与其他变量无关。
这些发现支持了TDF/FTC PrEP在HIV血清阴性年轻男性中的短期肾脏安全性，并表明内分泌紊乱（PTH-FGF23）是该年龄组中TDF相关BMD下降的主要原因。
NCT01769469。
