Department of Global Health, University of Washington, Seattle, WA 98104, USA.
N Engl J Med. 2012 Aug 2;367(5):399-410. doi: 10.1056/NEJMoa1108524. Epub 2012 Jul 11.
BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
背景：抗逆转录病毒药物的暴露前预防是预防人类免疫缺陷病毒 1 型（HIV-1）感染的一种很有前途的方法，适用于异性恋人群。
方法：我们在肯尼亚和乌干达进行了一项随机试验，评估口服抗逆转录病毒药物用于 HIV-1 血清不一致的异性恋夫妇的暴露前预防。每个夫妇中的 HIV-1 血清阴性伴侣被随机分配到三种研究方案之一：每日一次替诺福韦（TDF）、替诺福韦-恩曲他滨（TDF-FTC）联合用药或匹配的安慰剂，并在 36 个月内每月随访。在入组时，根据国家指南，HIV-1 血清阳性伴侣不符合接受抗逆转录病毒治疗的条件。所有夫妇都接受了标准的 HIV-1 治疗和预防服务。
结果：我们共纳入了 4758 对夫妇，其中 4747 对夫妇接受了随访：1584 对接受 TDF 治疗，1579 对接受 TDF-FTC 治疗，1584 对接受安慰剂治疗。接受随访的夫妇中，有 62%的 HIV-1 血清阴性伴侣为男性。在 HIV-1 血清阳性参与者中，中位数 CD4 计数为每立方毫米 495 个细胞（四分位间距为 375 至 662）。在研究期间，有 82 名血清阴性参与者发生了 HIV-1 感染，TDF 组 17 例（发病率为每 100 人年 0.65 例），TDF-FTC 组 13 例（发病率为每 100 人年 0.50 例），安慰剂组 52 例（发病率为每 100 人年 1.99 例），表明 TDF 可使 HIV-1 发病率降低 67%（95%置信区间[CI]为 44 至 81；P<0.001），TDF-FTC 可使 HIV-1 发病率降低 75%（95%CI 为 55 至 87；P<0.001）。TDF-FTC 和 TDF 单独预防 HIV-1 的效果没有显著差异（P=0.23），并且两种研究药物均显著降低了男性和女性的 HIV-1 发病率。各组的严重不良事件发生率相似。在接受活性治疗的 8 名参与者中，有 8 名在基线时被发现感染了 HIV-1，其中 2 名在研究期间出现了抗逆转录病毒耐药。
结论：口服 TDF 和 TDF-FTC 均可预防异性恋男性和女性感染 HIV-1。（由比尔及梅琳达·盖茨基金会资助；Partners PrEP 临床试验注册编号，NCT00557245。）
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