Chemoprophylaxis for HIV Prevention in Men Supplement

描述（由申请人提供）：联合国艾滋病规划署估计，尽管人们普遍知道避孕套的保护作用，但每年仍有500万人感染艾滋病毒。目前还没有疫苗问世，免疫保护的相关因素也没有明确定义。虽然男性包皮环切术在异性恋男性中似乎有50%至60%的保护作用，但这种方法对暴露于直肠的男性的价值尚不清楚。口服化学预防是一种很有前途的HIV预防方法，在其他传染病中有证实的先例。2005年8月，一项名为“男性艾滋病毒化学预防”的预防试验获得资助，编号为U01-AI064002。该临床试验将评估临床前研究中最有希望的候选药物的有效性和安全性：联合配制恩曲他滨200mg /富马酸替诺福韦二oproxl 300mg （FTC/TDF）。在该项目的头16个月里，在与脆弱社区、医疗专家、政府官员和其他有关方面进行广泛全球和地方协商的基础上，充分制定了议定书、程序和文书。该方案现已得到美国国立卫生研究院、美国食品药品监督管理局、旧金山、秘鲁和厄瓜多尔的伦理委员会以及厄瓜多尔卫生部的批准。为增加对研究参与者的保护而修改的方案增加了项目的总成本，为此现在需要补充资金。最终的项目将招募1400名男性，他们将以1:1的比例随机接受每日口服FTC/TDF和安慰剂，并随访长达96周，观察血清转化（目标1）、不良事件（目标2）、HBV相互作用（目标3）、骨和脂肪效应（目标4）、血清转化结果（目标5）和风险行为（目标6）。研究地点选择在最近的调查和试验中HIV-1感染发生率最高，具有良好临床实践所需的基础设施，并代表广泛的人类遗传和文化多样性。样本量足以检测艾滋病毒-1预防的成本效益水平，作为概念的证明。本研究对男性的关注是对亚洲和非洲女性临床试验的补充。化学预防的安全性和有效性在男性和女性中可能存在差异，这是由于生殖生物学、通常暴露于HIV的粘膜表面、行为差异和药代动力学的差异。这项研究的最终目的是通过保护有感染艾滋病毒风险的男性来打破艾滋病毒-1的流行循环，并可能使他们的女性性伴侣和未来的孩子免受伤害。

DESCRIPTION (provided by applicant): UNAIDS estimates 5 million new HIV infections occur every year despite widespread knowledge of the protective effects of condoms. A vaccine is not yet in sight, and the correlates of immune protection are not defined. While male circumcision appears to be 50 to 60% protective in heterosexual men, the value of this approach for rectally exposed men is not known. Oral chemoprophylaxis is a promising approach to HIV prevention with proven precedent in other infectious diseases. A prevention trial titled "Chemoprophylaxis for HIV Prevention in Men" was funded in August 2005 as U01-AI064002. The clinical trial will evaluate the efficacy and safety of the most promising candidate identified in pre-clinical studies: co-formulated emtricitabine 200 mg / tenofovir disoproxl fumarate 300 mg (FTC/TDF). In the first 16 months of this project, the protocol, procedures, and instruments have been fully developed based on extensive global and local consultations with vulnerable communities, medical experts, government officials, and other interested parties. The protocol has now been approved by the NIH, the US FDA, ethical committees in San Francisco, Peru and Ecuador, and the Ecuadorian Ministry of Health. Protocol changes for increasing protections for research participants have increased total project costs, for which supplemental funds are now requested. The final project will enroll 1400 men who will be randomized 1:1 to receive daily oral FTC/TDF versus placebo and followed for up to 96 weeks for seroconversion (aim 1), adverse events (aim 2), HBV interactions (aim 3), bone and fat effects (aim 4), seroconverter outcomes (aim 5), and risk behavior (aim 6). Study sites are selected that have the highest incidence of HIV-1 infection in recent surveys and trials, have the required infrastructure for Good Clinical Practices, and represent extensive human genetic and cultural diversity. The sample size is sufficient to detect cost-effective levels of HIV-1 prevention as a proof of concept. The focus on men in this study complements clinical trials in women in Asia and Africa. The safety and efficacy of Chemoprophylaxis may differ in men and women due to differences in reproductive biology, the mucosal surfaces that are typically exposed to HIV, behavioral differences, and pharmacokinetics. This research ultimately aims to break the epidemic cycle of HIV-1 by protecting men at risk for HIV, and may spare their female sexual partners and their future children.