Solomon Marc M, Lama Javier R, Glidden David V, Mulligan Kathleen, McMahan Vanessa, Liu Albert Y, Guanira Juan Vicente, Veloso Valdilea G, Mayer Kenneth H, Chariyalertsak Suwat, Schechter Mauro, Bekker Linda-Gail, Kallás Esper Georges, Burns David N, Grant Robert M
aThe Gladstone Institutes bUniversity of California cBridge HIV, San Francisco Department of Public Health, San Francisco, USA dInvestigaciones Medicas en Salud eAsociación Civil Impacta Salud y Educación, Lima, Peru fInstituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil gFenway Institute, Fenway Health, Boston, USA hResearch Institute for Health Sciences iDepartment of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand jProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil kDesmond Tutu HIV Centre and Department of Medicine, University of Cape Town, Cape Town, South Africa lDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo mInstituto de Investigação em Imunologia, CEP 05403-900 Cerqueira Cesar, São Paulo, Brazil nNational Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
AIDS. 2014 Mar 27;28(6):851-9. doi: 10.1097/QAD.0000000000000156.
Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons.
The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy.
There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy.
In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.
替诺福韦酯（TDF）暴露前预防可降低通过性行为感染HIV的几率。我们旨在评估TDF在未感染HIV人群中的肾脏安全性。
暴露前预防倡议（iPrEx）研究将2499名HIV血清阴性的男性及与男性发生性行为的变性女性随机分为两组，一组每日口服与恩曲他滨联合配方的TDF（FTC/TDF），另一组服用安慰剂。测量随机治疗期间及停药后的血清肌酐和磷水平，并通过Cockcroft - Gault方程估算肌酐清除率（CrCl）。在一项子研究中测量近端肾小管病变指标（磷和尿酸排泄分数、尿蛋白和葡萄糖）。
与安慰剂组相比，活性药物组的CrCl从基线开始有小幅但具有统计学意义的下降，在第4周首次观察到（平均变化：-2.4 vs. -1.1 ml/min；P = 0.02），持续到最后一次治疗访视（平均变化：+0.3 vs. +1.8 ml/min；P = 0.02），在停止暴露前预防后恢复（平均变化：-0.1 vs. 0.0 ml/min；P = 0.83）。按药物检测分层时该效应得到证实。FTC/TDF对CrCl的影响不因种族、年龄或高血压病史而有所不同。治疗组之间血清磷酸盐趋势无差异。在子研究中，两名接受安慰剂的参与者有肾小管病变指标。
在HIV血清阴性的男男性行为者中，随机分配接受FTC/TDF与CrCl非常轻微的非进行性下降相关，这种下降是可逆的，通过常规血清肌酐监测即可处理。
