Trial of Male Circumcision to Reduce HIV Incidence

描述（由申请人提供）：超过40项流行病学研究和一项临床试验发现男性包皮环切术（MC）对男性感染艾滋病毒有保护作用。对非洲研究的荟萃分析表明，经调整后，一般人群的艾滋病毒风险降低了45%，高危人群降低了70%。在南非进行的一项临床试验表明，其保护效果为60%，按方案分析显示，其保护效果为76%。此外，未割包皮的男子感染某些性传播感染的风险更高，这反过来又增加了艾滋病毒的易感性。这些数据促使人们呼吁将男性包皮环切术视为一项艾滋病毒预防战略，特别是在艾滋病毒高流行地区。然而，在艾滋病规划署、世界卫生组织、儿童基金会和其他组织举行的会议上，研究人员和决策者得出结论，在倡导MC用于预防艾滋病毒之前，需要有来自更多随机对照试验的明确证据证明其具有保护作用。本申请寻求支持继续在肯尼亚基苏木进行男性包皮环切术的随机对照试验。主要目的是评估MC在减少性活跃的年轻男性中艾滋病毒发病率方面的有效性。18-24岁的未行包皮环切术的艾滋病毒血清阴性男性被随机分为治疗组（包皮环切）或对照组，随访两年，定期进行行为和性传播感染评估，以及艾滋病毒检测和咨询。主要终点是HIV发病率，其次是手术并发症、性传播感染发病率和行为风险。2005年9月完成了2784名年轻男子的登记。这一样本量将提供80%的能力，可在两年内将艾滋病毒发病率降低50%。到目前为止，由于参与者没有报告研究访问，只有11%的人年被遗漏；艾滋病毒和性传播感染发生率与最初的预测一致。因此，这项研究正在按计划实现最初的目标，并为男性包皮环切术是否能降低艾滋病毒发病率的问题提供一个明确的答案。由于任何MC的影响都可能在24个月后通过行包皮环切术与未行包皮环切术男性的不同行为变化而被稀释，我们建议在参与者的亚队列中延长随访时间超过两年。由于MC在非洲艾滋病毒高流行区域很少实行，因此这项试验的结果可能对艾滋病毒/艾滋病大流行产生非常重大的影响。

DESCRIPTION (provided by applicant): Over 40 epidemiological studies and one clinical trial have found a protective effect of male circumcision (MC) against HIV acquisition in men. A meta-analysis of African studies has demonstrated an adjusted reduction in HIV risk of 45% in the general population and 70% among high risk groups. A clinical trial in South Africa demonstrated a 60% protective effect, with a 76% effect in a per-protocol analysis. In addition, uncircumcised men are at higher risk for acquisition of certain sexually transmitted infections (STIs), which in turn increase HIV susceptibility. These data have led to calls for male circumcision to be considered as an HIV prevention strategy, especially in areas of high HIV prevalence. However, at meetings held by UNAIDS, the World Health Organization, UNICEF and others, researchers and policy makers have concluded that clear evidence of a protective effect from additional randomized controlled trials (RCTs) is required before MC can be advocated for HIV prevention. This application seeks support for continuation of a randomized controlled trial of male circumcision in Kisumu, Kenya. The main objective is to assess the effectiveness of MC in reducing HIV incidence in young, sexually active men. Uncircumcised HIV seronegative men aged 18-24 years are randomized into either the treatment (circumcision) or control arm and followed for two years, with regular behavioral and STI assessments, as well as HIV testing and counseling. The primary endpoint is HIV incidence, with surgical complications, STI incidence, and behavioral risk as secondary outcomes. Enrollment of 2784 young men was completed September 2005. This sample size will provide 80% power to detect a 50% reduction in HIV incidence over two years. So far, just 11% of person-years have been missed due to participants not reporting for study visits; rates of HIV and STI incidence are consistent with original projections. Thus the study is on track to meet the original objectives and to provide a clear answer to the question of whether male circumcision reduces HIV incidence. Because any effect of MC could be diluted after 24 months through differential changes in behavior by circumcised versus uncircumcised men, we propose to extend follow-up beyond two years on a sub-cohort of participants. Since MC is little practiced in the high HIV prevalence regions of Africa, the results of this trial could have a very significant impact on the HIV/AIDS pandemic.