生殖器溃疡病和单纯疱疹病毒 2 型对男性包皮环切术预防艾滋病毒效果的影响：来自 Rakai 试验的分析。

Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: Analyses from the Rakai trials.

机构信息

Johns Hopkins University, Baltimore, Maryland, United States of America.

出版信息

PLoS Med. 2009 Nov;6(11):e1000187. doi: 10.1371/journal.pmed.1000187. Epub 2009 Nov 24.

DOI:10.1371/journal.pmed.1000187

PMID:19936044

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2771764/

Abstract

BACKGROUND

Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC.

METHODS AND FINDINGS

HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43-0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51-0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30-0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (chi(2)p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15-0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19-1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49-1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0-38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI -1.2 to 77.1).

CONCLUSIONS

Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.

摘要

背景

随机试验表明，男性包皮环切术（MC）可降低 HIV 和单纯疱疹病毒 2 型（HSV-2）感染以及有症状的生殖器溃疡病（GUD）的发生率。我们评估了 GUD 和 HSV-2 在 MC 对 HIV 提供的保护中的作用。

方法和发现

在乌干达 Rakai 的两项随机试验中，HIV 未感染者被随机分配至立即（n=2756）或延迟 MC（n=2775）。在入组时以及随访 6、12 和 24 个月时，确定 GUD 症状、HSV-2 状态和 HIV 获得情况。通过 PCR 评估溃疡病因。我们估计了包皮环切术与未包皮环切术男性中 GUD 的患病率和患病率风险比（PRR），并评估了 HSV-2 血清阳性状态作为 GUD 的风险修饰因素的作用。我们估计了 MC 对 HIV 获得的影响中，由有症状的 GUD 和 HSV-2 感染介导的比例。包皮环切术显著降低了 HSV-2 血清阴性男性（PRR=0.51，95%置信区间[CI]0.43-0.74）、HSV-2 血清阳性男性（PRR=0.66，95%CI0.51-0.69）和 HSV-2 血清转换者（PRR=0.48，95%CI0.30-0.79）中的有症状 GUD。通过 PCR 检测到的由 HSV-2 引起的急性溃疡的比例在包皮环切术男性中为 48.0%，在未包皮环切术男性中为 39.3%（chi(2)p=0.62）。包皮环切术降低了 HSV-2 血清阴性男性的 HIV 获得风险（发病率比[IRR]0.34，95%CI0.15-0.81），并且可能降低了 HSV-2 血清转换者的 HIV 获得风险（IRR=0.56，95%CI0.19-1.57；不显著），但不能降低在入组时就存在 HSV-2 感染的男性的 HIV 获得风险（IRR=0.89，95%CI0.49-1.60）。在包皮环切术男性中，通过减少有症状的 GUD 介导的 HIV 获得减少的比例为 11.2%（95%CI5.0-38.0），通过减少 HSV-2 发病率介导的比例为 8.6%（95%CI-1.2 至 77.1）。