Havens Peter L, Long Dustin, Schuster Gertrud U, Gordon Catherine M, Price Georgine, Wilson Craig M, Kapogiannis Bill G, Mulligan Kathleen, Stephensen Charles B
Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee, WI, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.
Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities.
Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses.
Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)D had the positive correlation similar to that found in vitamin D deficiency.
TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health.
NCT01751646 (ATN 109) and NCT01769469 (ATN 117).
富马酸替诺福韦二吡呋酯（TDF）可使血清甲状旁腺激素（PTH）和1,25-二羟维生素D（1,25-(OH)D）升高，并降低骨密度（BMD）。对TDF相关骨密度丢失进行最佳治疗需要了解这些异常的主要原因。
对两项关于青少年使用TDF的研究数据进行二次分析，比较三组不同TDF暴露情况的PTH、25-羟维生素D（25-OHD）和1,25-(OH)D之间的关系：未感染HIV的青少年在基线时（未暴露于TDF）以及接受TDF治疗12周后（短期TDF暴露）参加TDF/恩曲他滨（FTC）预防HIV暴露前预防（PrEP）试验；以及在研究入组时接受含TDF的联合抗逆转录病毒治疗（cART）至少6个月的感染HIV的青少年（长期TDF暴露）。通过相关性分析评估关系。
参与者年龄在17至24岁之间，超过50%为黑人/非裔美国人。在未接受TDF治疗的人群中，PTH与25-OHD具有生理上适当的负相关性（r=-0.3504，P=0.004）。接受TDF治疗的组中，PTH与25-OHD之间的相关性较弱或不存在。在感染HIV的人群中进行长期TDF治疗后，25-OHD和1,25-(OH)D具有与维生素D缺乏时相似的正相关性。
TDF改变了25-OHD与PTH之间的关系，这表明在使用TDF进行PrEP或cART的人群中，可能需要高于通常的血清25-OHD浓度目标来降低PTH并优化骨骼健康。
NCT01751646（ATN 109）和NCT01769469（ATN 117）。
