Randomized Trial of Clinical Safety of Daily Oral Tenofovir Disoproxil Fumarate Among HIV-Uninfected Men Who Have Sex With Men in the United States
Randomized Trial of Clinical Safety of Daily Oral Tenofovir Disoproxil Fumarate Among HIV-Uninfected Men Who Have Sex With Men in the United States
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DOI：
10.1097/qai.0b013e31828ece33
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发表时间：
2013-09-01
影响因子：
3.6
通讯作者：
Buchbinder, Susan P.
中科院分区：
文献类型：
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作者：
Grohskopf, Lisa A.;Chillag, Kata L.;Buchbinder, Susan P.
目的：评价每日富马酸替诺福韦二氧吡酯（TDF）在hiv阴性男男性行为者中的临床安全性。设计：随机、双盲、安慰剂对照试验。参与者以1:1:1的比例随机分配到立即或延迟的研究药物（TDF，每天口服300毫克，或安慰剂）。方法：在亚特兰大、波士顿和旧金山招募了400名在过去12个月内报告与另一名男性肛交的健康的未感染艾滋病毒的男性。每隔3个月评估一次HIV血清状态、临床和实验室不良事件（ae）、依从性（药片数量、用药事件监测系统和自我报告）以及性和其他社会行为数据，持续24个月。主要结局是临床安全性，通过不良反应发生率和实验室异常进行评估。结果：373名（93%）参与者（186名TDF和187名安慰剂）开始使用研究药物，其中325名（87%）完成了最终的研究访问。在334名（90%）参与者中报告的2428例ae中，2366例（97%）为轻度或中度严重程度。通常报道的ae的频率在TDF组和安慰剂组之间没有显著差异。在多变量分析中，TDF接受者更容易出现背痛（P = 0.04）；这些报告与骨折或其他客观发现无关。无>= 3级肌酐升高；1级和2级肌酐升高与接受TDF无关。研究药物剂量的估计百分比按药片计数为92%，用药事件监测系统为77%。发生了7例血清转换：安慰剂组4例，未服用研究药物的延迟组3例。结论：每日口服TDF耐受性良好，依从性合理。未发现明显的肾脏问题。
Objectives: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men.Design: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1: 1: 1: 1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo).Methods: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities.Results: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade >= 3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug.Conclusions: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.