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）对男性艾滋病毒感染具有保护作用。对非洲研究的荟萃分析表明，调整后的艾滋病毒风险在普通人群中降低了45%，在高危人群中降低了70%。在南非进行的一项临床试验显示，60%的保护效果，在符合方案分析中的效果为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作为一项艾滋病毒预防战略，特别是在艾滋病毒高发地区。然而，在联合国艾滋病规划署、世界卫生组织、联合国儿童基金会和其他机构举行的会议上，研究人员和政策制定者得出结论，在提倡将MC用于艾滋病毒预防之前，需要有更多随机对照试验（RCT）的明确证据证明其保护作用。本申请寻求对在肯尼亚基苏穆继续进行男性包皮环切术随机对照试验的支持。主要目的是评估MC在降低性活跃的年轻男性艾滋病毒发病率方面的有效性。年龄在18-24岁的未接受包皮环切术的HIV血清阴性男性被随机分为治疗组（包皮环切术）或对照组，并随访两年，定期进行行为和STI评估，以及HIV检测和咨询。主要终点是HIV发病率，次要终点是手术并发症、STI发病率和行为风险。2005年9月完成了2 784名青年男子的入学。这一样本量将提供80%的把握度来检测两年内艾滋病毒发病率降低50%的情况。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病率与最初的预测一致。因此，这项研究正在实现最初的目标，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明确的答案。由于任何影响MC可以稀释后24个月通过不同的行为变化，包皮环切术与未包皮环切术的男性，我们建议延长随访超过两年的参与者的子队列。由于MC在非洲艾滋病毒高流行地区很少实施，因此这项试验的结果可能对艾滋病毒/艾滋病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.