A Randomized Trial of the Copper IUD versus DMPA for HIV Prevention in Women

描述（由申请人提供）：2009年，估计全世界有超过3300万人感染艾滋病毒，其中近1600万人是妇女。大多数人生活在撒哈拉以南非洲，那里60%的艾滋病毒感染者是妇女。撒哈拉以南非洲使用激素避孕的妇女比例也很高，特别是注射用醋酸甲羟孕酮（DMPA）。虽然最近的研究已经证明了抗逆转录病毒暴露前预防（PrEP）在降低艾滋病毒感染风险方面的疗效，但在CAPRISA-004研究中，接受替诺福韦凝胶的实验组中艾滋病毒感染率仍然很高（每100名女性年5.6例）;这项研究中的大多数女性使用DMPA。确定激素避孕是否对艾滋病毒感染有影响是一个关键的悬而未决的公共卫生问题。我们正在申请资金支持一项多中心、随机试验的初步开发，以评估使用铜宫内节育器与DMPA预防妇女感染艾滋病毒的影响。未来试验的次要目的是评估年龄或HSV-2感染状态是否会改变避孕药具使用对HIV感染的任何影响，以及研究组是否对妊娠和避孕药具继续率有任何影响。该试验将在南部非洲的2-3个临床研究中心进行。我们将使用或希望使用注射避孕药的女性随机分为DMPA每3个月一次或铜宫内节育器。参与者将每3个月返回诊所进行一次包括艾滋病毒检测在内的诊所访问，为期一年。该R4计划补助金将用于支持研究者的时间、差旅和用品，以：a）建立多学科方案团队; B）确定合作者和临床研究中心， 招募、入组和随访足够数量的合格受试者，并进行适当的 知情同意、临床和数据收集程序，c）制定必要的研究文件，包括研究方案、统计和数据管理计划以及研究程序手册，d）制定整个研究期间的详细预算，包括适当的分包合同，以及e）与合作者合作制定知情同意书和培训材料。这些目标的完成预计将导致R 01赠款申请的开发和提交。我们预计，R34规划期的时间将提高未来试验的效率和质量。据估计，2009年全世界有260万人新感染艾滋病毒，因此迫切需要简单、有效和廉价的预防方法。如果宫内节育器能够降低原本使用注射避孕药的妇女感染艾滋病毒的风险，我们的研究结果将为实现到2015年制止并开始扭转艾滋病毒/艾滋病蔓延的千年发展目标做出重要贡献。 公共卫生相关性：我们正在申请资金支持一项多中心随机试验的初步开发，以评估使用铜IUD与DMPA预防妇女感染艾滋病毒的影响。由于艾滋病毒感染主要影响育龄妇女，确定激素避孕是否对艾滋病毒感染有影响是一个关键的未回答的公共卫生问题。拟议的临床试验规划补助金将支持临床试验的重要规划活动，包括确定合作者和临床研究中心、制定必要的研究文件（包括研究方案和程序手册）以及制定详细的试验预算。

DESCRIPTION (provided by applicant): Over 33 million people worldwide are estimated to be living with HIV in 2009, with almost 16 million of these being women. Most live in Sub-Saharan Africa where 60% of HIV infections are in women. Sub-Saharan Africa also has a high proportion of women using hormonal contraception, particularly the injectable progestin depot-medroxyprogesterone acetate (DMPA). While recent studies have documented the efficacy of antiretroviral pre-exposure prophylaxis (PrEP) in reducing risk of HIV acquisition, in the CAPRISA-004 study, HIV incidence remained high (5.6 per 100 woman-years) in the experimental group receiving tenofovir gel; most women in this study used DMPA. Determining whether hormonal contraception has an effect on HIV acquisition is a critical unanswered public health issue. We are requesting funding to support initial development of a multi- center, randomized trial to evaluate the impact of use of the copper IUD versus DMPA for prevention of HIV acquisition in women. Secondary aims of the future trial are to evaluate whether age or HSV-2 infection status modifies any effect of contraceptive use on HIV acquisition, and whether study arm has any impact on pregnancy and contraceptive continuation rates. The trial will be conducted at 2-3 clinical research sites in Southern Africa. We will randomize women using or wanting to use injectable contraception to DMPA every 3 months or copper IUDs. Participants will return for clinic visits including HIV testing every 3 months for a period of one year. This R4 planning grant will be used to support investigators' time, travel, and supplies to: a) establish te multidisciplinary protocol team; b) identify collaborators and clinical sites that can successfully recruit, enroll, and follow-up sufficient numbers of eligible participants, and conduct appropriate informed consent, clinical and data collection procedures, c) develop necessary study documents including the study protocol, the statistical and data management plans and the study manual of procedures, d) develop a detailed budget for the entire research study period including for appropriate sub-contracts, and e) work with collaborators to develop informed consent forms and training materials. Completion of these aims is expected to result in the development and submission of an R01 grant application. We anticipate that the time dedicated to the R34 planning period will enhance the efficiency and quality of the future trial. With an estimated 2.6 million new HIV infections worldwide in 2009, the need for simple, effective and inexpensive prevention approaches is critical. If IUDs can lower the risk of HIV acquisition in a population of women who would otherwise use injectable contraceptives, our results could make an important contribution to the Millennium Development Goal of halting and beginning to reverse the spread of HIV/AIDS by 2015. PUBLIC HEALTH RELEVANCE: We are requesting funding to support initial development of a multi-center, randomized trial to evaluate the impact of use of the copper IUD versus DMPA for prevention of HIV acquisition in women. Because HIV infection primarily affects women of reproductive age, determining whether hormonal contraception has an effect on HIV acquisition is a critical unanswered public health question. The proposed Clinical Trial Planning Grant will support important planning activities for the clinical trial including the identification of collaborators and clinical sites, development of necessary study documents including the study protocol and manual of procedures and creation of a detailed budget for the trial.