FHI 360, Research Triangle Park, North Carolina, USA.
N Engl J Med. 2012 Aug 2;367(5):411-22. doi: 10.1056/NEJMoa1202614. Epub 2012 Jul 11.
Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.
In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety.
HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy.
Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).
抗逆转录病毒药物的暴露前预防在一些试验中已被证实能有效预防人类免疫缺陷病毒（HIV）感染，但在另一些试验中则不然。
在这项随机、双盲、安慰剂对照试验中，我们将 2120 名来自肯尼亚、南非和坦桑尼亚的 HIV 阴性女性随机分配，每日接受一次替诺福韦酯富马酸二吡呋酯和恩曲他滨（TDF-FTC）或安慰剂治疗。主要目的是评估 TDF-FTC 预防 HIV 感染的效果，并评估安全性。
TDF-FTC 组发生 33 例 HIV 感染（发病率为每 100 人年 4.7 例），安慰剂组发生 35 例（发病率为每 100 人年 5.0 例），TDF-FTC 组的估计风险比为 0.94（95%置信区间，0.59 至 1.52；P=0.81）。TDF-FTC 组恶心、呕吐或丙氨酸氨基转移酶升高的女性比例明显高于安慰剂组（P=0.04、P<0.001 和 P=0.03）。因肝或肾异常而停药的比例在 TDF-FTC 组（4.7%）高于安慰剂组（3.0%，P=0.051）。TDF-FTC 组中不到 40%的 HIV 未感染女性在与女性血清转换窗口期相匹配的就诊时，有近期用药的证据。由于缺乏疗效，该研究于 2011 年 4 月 18 日提前终止。
与安慰剂相比，TDF-FTC 预防并未显著降低 HIV 感染率，且与副作用发生率增加相关。尽管进行了大量的咨询，但药物依从性似乎较低。（由美国国际开发署和其他机构资助；FEM-PrEP 临床试验.gov 编号，NCT00625404）。
