Tenofovir-based preexposure prophylaxis for HIV infection among African women.
Tenofovir-based preexposure prophylaxis for HIV infection among African women.
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DOI：
10.1056/nejmoa1402269
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发表时间：
2015-02-05
期刊：
影响因子：
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通讯作者：
VOICE Study Team
中科院分区：
文献类型：
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作者：
Marrazzo JM;Ramjee G;Richardson BA;Gomez K;Mgodi N;Nair G;Palanee T;Nakabiito C;van der Straten A;Noguchi L;Hendrix CW;Dai JY;Ganesh S;Mkhize B;Taljaard M;Parikh UM;Piper J;Mâsse B;Grossman C;Rooney J;Schwartz JL;Watts H;Marzinke MA;Hillier SL;McGowan IM;Chirenje ZM;VOICE Study Team
育龄妇女需要采取有效的干预措施，以防止感染人类免疫缺陷病毒1型（HIV-1）。我们进行了一项随机、安慰剂对照试验，以评估南非、乌干达和津巴布韦妇女每天口服替诺福韦酯（TDF）、口服替诺福韦-恩曲他滨（TDF-FTC）或1%替诺福韦（TFV）阴道凝胶作为暴露前预防HIV-1感染的治疗。每月进行HIV-1检测，每季度评估血浆TFV水平。在接受筛查的12，320名妇女中，有5029人参加了这项研究。在5509人年的随访中，研究中的保留率为91%。共发生312例HIV-1感染; HIV-1感染率为每100人年5.7例。在改良的意向治疗分析中，TDF的有效性为-49.0%（感染的风险比，1.49; 95%置信区间[CI]，0.97 - 2.29），TDF-FTC为−4.4%（风险比，1.04; 95% CI，0.73 - 1.49），TFV凝胶组为14.5%（风险比，0.85; 95% CI，0.61 - 1.21）。在随机样本中，分别在随机分配接受TDF、TDF-FTC和TFV凝胶的参与者的30%、29%和25%的可用血浆样本中检测到TFV。TFV检测的独立预测因素包括已婚、年龄大于25岁和多产。血浆中TFV的检测与预测HIV-1获得的特征呈负相关。随机分配接受口服TDF-FTC的受试者血清肌酐水平升高的频率高于分配接受口服安慰剂的受试者（1.3% vs. 0.2%，P = 0.004）。我们没有观察到其他不良事件的频率有显著差异。在意向治疗分析中，我们评估的药物方案均未降低HIV-1感染率。对研究药物的依从性低。
Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir–emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was −49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), −4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.