博茨瓦纳异性传播 HIV 中抗逆转录病毒的预先暴露预防。

Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

机构信息

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, USA.

出版信息

N Engl J Med. 2012 Aug 2;367(5):423-34. doi: 10.1056/NEJMoa1110711. Epub 2012 Jul 11.

DOI:10.1056/NEJMoa1110711

PMID:22784038

Abstract

BACKGROUND

Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain.

METHODS

We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants.

RESULTS

A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03).

CONCLUSIONS

Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

摘要

背景

抗逆转录病毒药物的暴露前预防已被证明可降低男男性行为者中的人类免疫缺陷病毒（HIV）传播；然而，其在异性恋者中的效果尚不确定。

方法

我们将 HIV 血清阴性的男性和女性随机分配接受替诺福韦酯和恩曲他滨（TDF-FTC）或匹配安慰剂，每日一次。每月安排研究访问，参与者接受综合预防服务包，包括 HIV 检测、药物依从性咨询、性传播感染管理、不良事件监测和个体化风险降低咨询；骨矿物质密度检测在一部分参与者中每半年进行一次。

结果

共有 1219 名男性和女性接受了随机分组（45.7%为女性），随访了 1563 人年（中位数为 1.1 年；最长为 3.7 年）。由于保留率低和逻辑限制，我们提前结束了研究，并通过有序的研究关闭而不是扩大入组来随访入组的参与者。TDF-FTC 组恶心（18.5%比 7.1%，P<0.001）、呕吐（11.3%比 7.1%，P=0.008）和头晕（15.1%比 11.0%，P=0.03）的发生率高于安慰剂组，但严重不良事件的发生率相似（P=0.90）。与接受安慰剂的参与者相比，接受 TDF-FTC 的参与者的骨矿物质密度显著下降。在入组时发生未识别的急性 HIV 感染的 1 名 TDF-FTC 组参与者中出现了 K65R、M184V 和 A62V 耐药突变。在包括研究期间感染的 33 名参与者的修改后的意向治疗分析中（TDF-FTC 组 9 名，安慰剂组 24 名；分别为每 100 人年 1.2 和 3.1 例感染），TDF-FTC 的疗效为 62.2%（95%置信区间为 21.5 至 83.4；P=0.03）。