Mugwanya Kenneth K, Wyatt Christina, Celum Connie, Donnell Deborah, Kiarie James, Ronald Allan, Baeten Jared M
*Department of Epidemiology, University of Washington, Seattle, WA;†Division of Disease Control, School of Public Health, Makerere University, Kampala, Uganda;‡Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY;Departments of §Global Health;‖Medicine, University of Washington, Seattle, WA;¶Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;#Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya; and**Department of Medicine, University of Manitoba, Winnipeg, Canada.
J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):374-80. doi: 10.1097/QAI.0000000000000868.
Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the reversibility of eGFR decline among HIV-uninfected adults discontinuing PrEP.
Data were from the Partners PrEP Study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women with baseline creatinine clearance ≥60 mL/min. Serum creatinine was measured quarterly while on-study medication and at month 1 and 2 after discontinuation. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation.
A total of 3924 individuals had a poststudy drug serum creatinine measurement after the scheduled drug discontinuation (1271 for TDF, 1308 for FTC-TDF, and 1345 for placebo); 65% were men, median age was 35 (range 18-64) years. Median time on study drug was 33 (interquartile range 25-36) months overall, and 36 months (interquartile range 30-36) for TDF and FTC-TDF. Mean eGFR at the last on-treatment visit was 129 mL·min·1.73 m for TDF and 128 mL·min·1.73 m for FTC-TDF versus 131 mL·min·1.73 m for placebo (2-3 mL·min·1.73 m mean decline for PrEP versus placebo, P ≤ 0.01), and this difference reversed by 4 weeks after drug discontinuation (mean eGFR at the first postdrug visit: 130 mL·min 1.73 m in all groups). More than 96% of participants had a confirmed >75% eGFR rebound to baseline level by 8 weeks after drug discontinuation, with similar proportions across treatment groups.
In this large, placebo-controlled study of TDF-based PrEP, the small reduction in mean eGFR associated with PrEP reversed within weeks after discontinuation.
富马酸替诺福韦二吡呋酯（TDF）暴露前预防（PrEP）的使用与估计肾小球滤过率（eGFR）出现虽小但具有统计学意义的下降有关。我们调查了停止PrEP的未感染HIV的成年人中eGFR下降的可逆性。
数据来自伙伴PrEP研究，这是一项针对基线肌酐清除率≥60 mL/分钟的非洲未感染HIV的男性和女性进行的每日口服TDF和恩曲他滨（FTC）-TDF PrEP的随机试验。在研究用药期间以及停药后第1个月和第2个月每季度测量血清肌酐。使用慢性肾脏病流行病学合作方程计算eGFR。
共有3924人在预定停药后进行了研究后药物血清肌酐测量（TDF组1271人，FTC-TDF组1308人，安慰剂组1345人）；65%为男性，中位年龄为35岁（范围18 - 64岁）。总体上研究药物的中位使用时间为33个月（四分位间距25 - 36个月），TDF和FTC-TDF组为36个月（四分位间距30 - 36个月）。末次治疗访视时TDF组的平均eGFR为129 mL·min·1.73 m²，FTC-TDF组为128 mL·min·1.73 m²，而安慰剂组为131 mL·min·1.73 m²（PrEP组与安慰剂组相比平均下降2 - 3 mL·min·1.73 m²，P≤0.01），停药4周后这种差异逆转（首次停药后访视时所有组的平均eGFR：130 mL·min·1.73 m²）。超过96%的参与者在停药后8周时确认eGFR反弹>75%至基线水平，各治疗组比例相似。
在这项基于TDF的PrEP的大型安慰剂对照研究中，与PrEP相关的平均eGFR的小幅下降在停药后数周内逆转。
