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

描述（由申请人提供）：据估计，2009年全球有超过3300万人感染艾滋病毒，其中近1600万是女性。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。撒哈拉以南非洲也有很高比例的妇女使用激素避孕，特别是注射黄体酮-醋酸甲羟黄体酮（DMPA）。虽然最近的研究已经证明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有效性，但在CAPRISA-004研究中，接受替诺福韦凝胶的实验组的艾滋病毒发病率仍然很高（每100名妇女年5.6例）；这项研究中的大多数女性都使用了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未解决的公共卫生问题。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对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2型单纯疱疹病毒感染状况是否会改变避孕药具使用对HIV感染的影响，以及研究分组是否对妊娠率和避孕药具延续率有任何影响。该试验将在南部非洲的2-3个临床研究地点进行。我们将随机选择每3个月使用或想要使用注射避孕的妇女到DMPA或铜宫内节育器。参与者将返回诊所就诊，包括每三个月进行一次艾滋病毒检测，为期一年。R4计划拨款将用于支持调查人员的时间、差旅和供应，以便：a)建立多学科方案小组；B)确定合作者和能够成功的临床地点

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.