Chemoprophylaxis for HIV Prevention in Men

男性艾滋病毒的化学预防

• 批准号: 7873381
• 负责人: Robert M. Grant
• 金额: $ 42.75万
• 依托单位: J. DAVID GLADSTONE INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-22 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7873381
• 关键词: AIDS prevention; Acute; Address; Adherence; Adverse event; Africa; Age; Americas; Anti-Retroviral Agents; Antiviral Agents; Asia; Attenuated; Authorization documentation; Awareness; Behavioral; Blinded; Budgets; CD4 Positive T Lymphocytes; California; Cell Count; Chemoprophylaxis; Child; Chronic Active Hepatitis; Cities; Clinical; Clinical Trials; Code; Creatinine; Data; Development Plans; Disclosure; Dose; Drug Kinetics; Drug resistance; Effectiveness; Enrollment; Epidemic; Evaluation; Face; Flare; Frequencies; Future; Genetic; Grant; Guidelines; HIV; HIV Infections; HIV-1; HIV-1 drug resistance; Health; Hepatic; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Virus; Human; Human Resources; Immunology; Incidence; Infection; Inflammation; Institutes; Instruction; Intention; Kidney Failure; Knowledge; Laboratories; Last Name; Letters; Licensing; Literature; Liver; Manuscripts; Methods; Minority; Modeling; Monitor; Monitoring Clinical Trials; Names; Oral; Participant; Patients; Persons; Peru; Pharmaceutical Preparations; Phase; Placebos; Prevalence; Prevention; Prevention Research; Principal Investigator; Printing; Procedures; Progress Reports; Publications; Randomized; Recruitment Activity; Reporting; Reproductive Biology; Research; Research Design; Research Infrastructure; Research Personnel; Research Project Grants; Resistance; Resources; Risk; Role; Safety; Sample Size; San Francisco; Serum; Severities; Sexual Partners; Site; Surface; Surveys; Tenofovir; Transaminases; United States; Universities; Upper arm; Ursidae Family; Vertebrates; Viral; Viral Load result; Virus; Woman; base; condoms; cost; density; high risk; high risk men; human subject; human subject protection; men; nonhuman primate; novel; performance site; prevent; product development; programs; rectal; total measurement Bilirubin; transmission process; virology

UNAIDS estimates that 14,000 persons are newly infected with HIV every day throughout the world, of which one half are between the ages of 15 and 24. New infections occur despite widespread awareness of the modes of HIV-1 transmission, and the protection afforded by condom use. Novel concepts for HIV-1 prevention are urgently needed. We propose to evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in a randomized and blinded trial of daily oral tenofovir 300 mg versus placebo among men in Peru, who have extremely high risk of acquiring HIV infection. Daily oral tenofovir 300 mg is selected for evaluation because it is FDA-licensed for human use, allows once- a-day dosing, is well-tolerated, is active against many drug resistant HIV-1 strains, and was demonstrated to be effective for prevention in non-human primate models. We propose to enroll 2100 men who will be randomized 1:1 to receive daily oral tenofovir 300 mg versus placebo and followed for 13 months for HIV-1 seroconversion (aim 1), adverse events (aim 2), and viral load, drug resistance and CD4 T cell count after seroconversion (aim 3). Study sites are selected in Peru because of their well-developed prevention research infrastructure and their demonstrated ability to recruit men at high risk for HIV infection with outstanding rates of retention. Recruitment will be derived from 3 cities in Peru that had the highest incidence of HIV-1 infection in two recent surveys, have the required infrastructure to support a closely monitored clinical trial, and represent enormous genetic and geophysical diversity. The sample size is sufficient to detect cost-effective levels of HIV-1 prevention. The trial also aims to evaluate the safety of this agent in HIV uninfected persons, including the incidence of mild renal insufficiency and liver inflammation. Chemoprophylaxis may involve durable benefits or risks as well, possibly leading to an attenuated course of infection due to early inhibition of viral replication or drug resistance. The proposed research addresses important gaps of knowledge directly, including the safety and efficacy of daily oral tenofovir chemoprophylaxis among men exposed to HIV after rectal exposure. This unique and essential information bears directly on HIV prevention in the Americas and will not be available after the completion of other studies planned for the United States, 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 sexual partners and their future children.

艾滋病规划署估计，全世界每天有14 000人新感染艾滋病毒，其中一半的人 年龄在15到24岁之间尽管对HIV-1的传播方式有了广泛的认识，但仍出现了新的感染病例。 传播，以及使用避孕套提供的保护。迫切需要新的HIV-1预防概念。 我们建议在随机和设盲的研究中评估化学预防用于预防艾滋病毒的安全性和有效性 在秘鲁极高风险感染艾滋病毒的男性中每日口服替诺福韦300 mg与安慰剂的试验 感染选择每日口服替诺福韦300 mg进行评估，因为它是FDA许可的人用药物，允许一次- 每天给药，耐受性良好，对许多耐药HIV-1菌株有活性， 在非人灵长类动物模型中有效预防。我们计划入组2100名男性，按1：1的比例随机分配至 每日口服替诺福韦300 mg与安慰剂，并随访13个月进行HIV-1血清转化（目的1）， 不良事件（目标2），以及血清转换后的病毒载量、耐药性和CD 4 T细胞计数（目标3）。研究中心 之所以在秘鲁被选中，是因为这些国家有完善的预防研究基础设施， 招募艾滋病毒感染高危男性，保留率高。招聘将来自3个城市 在最近两次调查中艾滋病毒-1感染率最高的秘鲁， 支持密切监测的临床试验，并代表了巨大的遗传和地球物理多样性。样本量 足以检测出符合成本效益的HIV-1预防水平。该试验还旨在评估这种药物在 未感染艾滋病病毒者，发病率包括轻度肾功能不全和肝脏炎症。化学预防 可能涉及持久的利益或风险，以及，可能导致一个衰减的过程中感染，由于早期 抑制病毒复制或耐药性。拟议的研究解决了重要的知识差距 直接，包括每日口服替诺福韦药物预防暴露于艾滋病毒的男性的安全性和有效性， 直肠暴露这一独特而重要的信息直接关系到美洲的艾滋病毒预防工作， 计划在美国、亚洲和非洲进行的其他研究完成后，这些研究将可供使用。的安全性和 由于生殖生物学、粘膜免疫学、免疫学和免疫学的差异， 通常暴露于HIV的表面、行为差异和药代动力学。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，打破艾滋病毒-1的流行周期， 未来的孩子。