每日口服替诺福韦和恩曲他滨替诺福韦预防暴露前用药可降低 HIV-1 未感染的异性恋男性和女性中单纯疱疹病毒 2 型的感染率：一项随机试验的亚组分析。

Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.

出版信息

Ann Intern Med. 2014 Jul 1;161(1):11-9. doi: 10.7326/M13-2471.

Abstract

BACKGROUND

Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2).

OBJECTIVE

To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition.

DESIGN

Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245).

SETTING

Multiple sites in Kenya and Uganda.

PARTICIPANTS

Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner.

INTERVENTION

Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo.

MEASUREMENTS

HSV-2 seroconversion.

RESULTS

A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years.

LIMITATION

Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available.

CONCLUSION

Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP.

PRIMARY FUNDING SOURCE

Bill & Melinda Gates Foundation.

摘要

背景

每日口服暴露前预防（PrEP）使用抗逆转录病毒药物替诺福韦二吡呋酯（TDF）单独或与恩曲他滨（FTC-TDF）联合使用，可降低 HIV-1 感染的风险。替诺福韦在体外对单纯疱疹病毒 2 型（HSV-2）具有活性。

目的

评估每日口服替诺福韦和 FTC-TDF 在预防 HSV-2 感染方面的疗效。

设计

随机、安慰剂对照试验的亚组分析，采用隐藏分组。（ClinicalTrials.gov：NCT00557245）。

地点

肯尼亚和乌干达的多个地点。

参与者

HIV-1 阴性和 HSV-2 阴性的异性恋男性和女性，由于伴侣 HIV-1 感染，他们具有 HIV-1 感染的高风险。

干预措施

每日口服一次替诺福韦二吡呋酯（TDF），单独或与恩曲他滨（FTC-TDF）联合使用，与安慰剂相比。

测量

HSV-2 血清转化。

结果

共有 131 名参与者出现 HSV-2 血清转化（1041 名接受替诺福韦或 FTC-TDF PrEP 分配的参与者中有 79 名[HSV-2 发病率，每 100 人年 5.6 例]，481 名接受安慰剂分配的参与者中有 52 名[HSV-2 发病率，每 100 人年 7.7 例]）。与安慰剂相比，每日口服 PrEP 治疗的 HSV-2 感染风险比为 0.70（95%CI，0.49 至 0.99；P = 0.047），绝对风险降低 2.1 例/100 人年。在 1044 名有 HSV-2 感染伴侣的参与者中，与安慰剂相比，PrEP 的风险比为 0.67（CI，0.46 至 0.98；P = 0.038），绝对风险降低 3.1 例/100 人年。