Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial
Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(08)60920-4
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发表时间：
2008-06-21
期刊：
影响因子：
168.9
通讯作者：
Corey, Lawrence
中科院分区：
文献类型：
--
作者：
Celum, Connie;Wald, Anna;Corey, Lawrence
背景：在许多观察性研究中，单纯疱疹病毒2型（HSV-2）感染与HIV-1感染风险增加两到三倍相关。我们研究了阿昔洛韦抑制HSV-2是否会降低HIV-1获得的风险。方法我们在hiv阴性、HSV-2血清阳性的非洲妇女和来自秘鲁和美国的男男性行为者（MSM）中进行了一项双盲、随机、安慰剂对照的III期试验。参与者被随机分配到每天两次阿昔洛韦400mg （n=1637）或匹配的安慰剂（n=1640），持续12-18个月，每月进行研究药物分配，依从性咨询，通过药丸计数和自我报告进行测量，以及风险降低咨询，每3个月进行生殖器检查和艾滋病毒检测。主要结果是HIV-1感染，其次是生殖器溃疡的发生率。分析的目的是治疗。本研究已在Clinicaltrials.gov注册，编号NCT00076232。主要数据集中包括3172名参与者（1358名女性，1814名男男性行为者）（阿昔洛韦组1581名，对照组1591名）。阿昔洛韦组HIV-1的发病率为3.9 / 100人年（在1935人-年随访期间为75例），安慰剂组为3.3 / 100人年（在1969人-年随访期间为64例），风险比为1。16 [95% ci 0。83 - 1.62])。检查时生殖器溃疡的发生率降低了47%(相对危险度为0。53[0.46-0.62])和HSV-2阳性生殖器溃疡在阿昔洛韦组中减少63%（0.37[0.31-0.45]）。阿昔洛韦组和安慰剂组对分配的研究药物的依从性分别为94%和94%，阿昔洛韦组和安慰剂组的预期剂量分别为85%和86%。两组在18个月时保留率均为85%（阿昔洛韦组1212人中有1028人，安慰剂组1208人中有1030人）。我们没有记录到与研究药物相关的严重事件。我们的研究结果表明，标准剂量的阿昔洛韦抑制治疗不能有效减少HSV-2血清阳性妇女和男男性行为者的HIV-1获得。需要新的策略来中断HSV-2和HIV-1之间的相互作用。资助美国国家过敏和传染病研究所、美国国家儿童健康和人类发展研究所、美国国家药物滥用研究所、美国国家精神卫生研究所、美国艾滋病研究办公室和葛兰素史克公司。
Background Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.Methods We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00076232.Findings 3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1 . 16 [95% CI 0 . 83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0 . 53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug.Interpretation Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.Funding US National Institute of Allergy and Infectious Diseases, US National Institute of Child Health and Human Development, US National Institute of Drug Abuse, US National Institute of Mental Health, US Office of AIDS Research, and GlaxoSmithKline.