HIV-1 的暴露前预防仍任重而道远

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目前有哪些针对 HIV-1 暴露前预防措施？

育龄期妇女需要有效的干预措施来预防人类免疫缺陷 1 型病毒（HIV-1）的感染。有研究表明：每天单独口服300mg 替诺福韦酯（TDF），或联合 200mg 恩曲他滨（FTC）（TDF-FTC）可以将 HIV-1 的感染风险降低50% 以上。基于这些研究结果，2012 年 7 月，美国食品和药物管理局（FDA）批准特鲁瓦达用于 HIV-1 的预防。美国疾病控制和预防中心（CDC）也发布了该药物的使用指南。

VIOCE 研究

来自美国西雅图港景医疗中心的研究人员设计了一项随机，安慰剂对照试验（VIOCE）来评价口服富马酸替诺福韦酯（TDF）治疗，口服替诺福韦–恩曲他滨（TDF-FTC），或 1% 泰诺福韦（TFV）阴道凝胶对育龄期妇女预防 HIV-1 感染的效果。结果让人失望。该研究结果发表在 2015 年 2 月的《新英格兰医学杂志》上。这项试验的参与人员主要来自南非，乌干达，津巴布韦。研究人员每月对参与人员进行 HIV-1 检测，每季度评价血浆 TFV 含量水平。研究人员共筛选了 12320 名妇女，其中 5029 人参加了这项研究。这项研究的随访时间共有 5509 人年。期间，共有 312 次 HIV-1 新发感染。

研究发现

1. 口服 TDF 预防 HIV-1 感染的有效率为 -49%，TDF-FTC 为 -4.4%， TFV 胶为 14.5%，无统计学差异。2. 通过随机样本检测，三组病人血浆中 TFV 的检出率分别为 30%，29% 和 25%。3. TFV 检出率的独立预测因子包括已婚，年龄在 25 岁以上，多次生产。4. TFV 检出率与 HIV 的感染率负相关。5. 与安慰剂相比，口服 TDF-FTC 组病人的血清肌酐水平比例较高。其他不良事件的发生频率无显著差异。

任重而道远

该研究表明口服富马酸替诺福韦酯（TDF）治疗，口服替诺福韦–恩曲他滨（TDF-FTC），或 1% 泰诺福韦（TFV）阴道凝胶都无法降低育龄期妇女感染 HIV -1 的风险。主要的原因是药物的依从性太差。因此，探索暴露前的治疗措施还任重而道远。

ORIGINAL ARTICLE

Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women

BACKGROUND

Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.)