Evaluation of the immunologic and genital tract changes among Malawian women

描述(由申请人提供)：这是为Jennifer Tang博士申请Fogarty国际中心K01国际研究科学家发展奖的申请书，她是北卡罗来纳大学教堂山分校专门从事计划生育和全球妇女健康的产科医生。唐博士在荷尔蒙避孕和艾滋病毒预防领域确立了自己作为年轻研究员的地位。这一K01奖项将为唐博士提供必要的支持，以实现以下目标：(1)学习与艾滋病毒感染相关的免疫学和生殖道标志物的基础知识；(2)获得高级研究设计和生物统计分析方面的经验；(3)成为在资源有限的情况下设计和实施随机对照试验的专家；以及(4)培养与临床和基础科学家进行多学科、远程合作的技能。为了实现这些目标，唐博士组建了一支导师团队，成员包括：美国初级导师、北卡罗来纳大学全球妇女健康部门主任、国际公认的艾滋病毒预防和治疗研究专家Jeffrey Stringer博士、马拉维初级导师、北卡罗来纳大学马拉维项目临床主任、撒哈拉以南非洲艾滋病毒和传染病研究专家Mina Hosseiniour博士、北卡罗来纳大学计划生育项目主任、激素避孕与艾滋病毒感染和治疗相互作用专家Gretchen Stuart博士；威廉·米勒博士，北卡罗来纳大学医疗保健流行病学和临床研究项目主任，分析方法专家，指导年轻研究人员实现研究独立性；克里斯蒂娜·阿贝尔博士，北卡罗来纳大学艾滋病研究免疫学核心中心副主任，粘膜免疫和艾滋病毒感染发病机制专家。了解孕激素(如甲羟孕酮或左旋诺孕酮)与艾滋病毒感染之间的潜在联系目前是妇女健康研究人员和政策制定者的关键研究重点。唐博士的研究将通过随机选择HIV阴性妇女接受Dpot甲羟孕酮(DMPA)注射或Jadelle(注册商标)左旋诺孕酮植入物，并比较在开始使用这些避孕药后发生的免疫学变化(目标1)和生殖道变化(目标2)来阐明这种关系。此外，她的研究还将评估在撒哈拉以南非洲艾滋病毒感染风险人群中进行DMPA和Jadelle(R)的长期随机对照试验的可行性和可接受性(目标3)。唐博士将把30名妇女随机分配到DMPA或Jadelle(注册商标)，并在避孕前后的多个时间点评估血清和生殖道中抗菌剂、炎性细胞因子和抗炎性细胞因子的水平，持续使用避孕药长达2年。这项研究将构成一项更大规模的多中心临床试验的基础，该试验将评估使用DMPA、Jadelle(R)和其他荷尔蒙避孕药的妇女感染艾滋病毒的风险。这项试验将由唐博士在四年职业发展奖励期结束前作为R01申请提交。

DESCRIPTION (provided by applicant): This is an application for a Fogarty International Center K01 International Research Scientist Development Award for Dr. Jennifer Tang, an obstetrician gynecologist specializing in family planning and global women's health at the University of North Carolina (UNC) at Chapel Hill. Dr. Tang is establishing herself as a young investigator in the areas of hormonal contraception and HIV prevention. This K01 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to learn the fundamentals of immunological and genital tract markers related to HIV acquisition; (2) to gain experience in advanced study design and biostatistical analysis; (3) to become an expert in the design and implementation of randomized controlled trials in resource-limited settings; and (4) to develop skills in multidisciplinary, long-distance collaboration with clinical and basic scientits. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a U.S primary mentor, Dr. Jeffrey Stringer, Director of the UNC Global Women's Health Division and an internationally-recognized research expert in HIV prevention and treatment; a Malawi primary mentor, Dr. Mina Hosseinipour, Clinical Director of UNC Project-Malawi and an expert in HIV and infectious disease research in sub-Saharan Africa; Dr. Gretchen Stuart, Director of the UNC Family Planning Program and expert in interactions between hormonal contraception and HIV infection and treatment; Dr. William Miller, Director of the UNC Program in Health Care Epidemiology and Clinical Research and an expert in analytic methods and mentoring young investigators toward research independence; and Dr. Kristina Abel, Associate Director of the UNC Center for AIDS Research Immunology Core and an expert in mucosal immunity and the pathogenesis of HIV infection. Understanding the potential association between progestins (such as medroxyprogesterone or levonorgestrel) and HIV acquisition is currently a critical research priority for women's health researchers and policymakers. Dr. Tang's research will focus on elucidating this relationship by randomizing HIV-negative women to receive the depot medroxyprogesterone acetate (DMPA) injection or the Jadelle(R) levonorgestrel implant and comparing the immunologic changes (Aim 1) and genital tract changes (Aim 2) that occur after initiation of these contraceptives. In addition, her research will evaluate the feasibility and acceptability of conducting a long-term randomized controlled trial of DMPA versus Jadelle(R) in a sub-Saharan African population at-risk for HIV acquisition (Aim 3). Dr. Tang will randomize 30 women to DMPA or Jadelle(R) and evaluate serum and genital tract levels of antimicrobials, inflammatory cytokines, and anti-inflammatory cytokines at multiple time points before and after contraceptive initiation, for up to 2 years of contraceptive use. This study will form the basis fo a larger, multicenter clinical trial that will evaluate the risk for HIV acquisition among women usin DMPA , Jadelle(R), and other hormonal contraceptives. This trial will be submitted by Dr. Tang as an R01 application before the end of the 4-year career development award period.