Evaluation of the immunologic and genital tract changes among Malawian women

摘要 这是福格蒂国际中心K 01国际研究科学家发展的申请 Jennifer Tang博士获奖，她是一位专门从事计划生育和全球妇女问题的妇产科医生。 在查佩尔山的北卡罗来纳州大学（北卡罗来纳州）的健康。唐博士正在建立自己作为一个年轻的 激素避孕和艾滋病毒预防领域的调查员。这个K 01奖将为唐博士 与必要的支持，以实现以下目标：（1）学习免疫学的基础知识 和生殖道标志物相关的艾滋病毒感染;（2）获得先进的研究设计经验， 生物统计学分析;（3）成为随机对照试验设计和实施的专家 在资源有限的情况下;和（4）发展多学科的技能，与 临床和基础科学家。为了实现这些目标，唐博士组建了一个指导团队， 一位美国的主要导师，Jeffrey Stringer博士，全球妇女健康部主任， 国际公认的艾滋病毒预防和治疗研究专家;马拉维初级导师，Mina博士 Hosseinipour，马拉维艾滋病项目临床主任， 撒哈拉以南非洲;非洲计划生育方案主任、 激素避孕与艾滋病毒感染和治疗之间的相互作用; 在卫生保健流行病学和临床研究和分析方法的专家， 指导年轻的研究人员走向研究独立;和克里斯蒂娜阿贝尔博士，副主任 艾滋病研究中心免疫学核心和粘膜免疫及发病机制专家 艾滋病毒感染。 了解孕激素（如甲羟孕酮或左炔诺孕酮）之间的潜在关联 艾滋病毒感染是妇女健康研究人员和决策者目前的一个重要研究重点。 博士唐的研究将集中在阐明这种关系，通过随机选择艾滋病毒阴性的妇女接受 长效醋酸甲羟孕酮（DMPA）注射剂或左炔诺孕酮植入剂， 比较免疫学变化（目标1）和生殖道变化（目标2）， 这些避孕药。此外，她的研究将评估进行一项 DMPA与Jadelle（R）在撒哈拉以南非洲高危人群中的长期随机对照试验 艾滋病毒感染（目标3）。唐博士将30名妇女随机分为DMPA或Jadelle（R），并评估血清和 多个时间点的生殖道抗菌剂、炎性细胞因子和抗炎性细胞因子水平 在开始避孕之前和之后，避孕时间最长为2年。这项研究将形成 这是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）和其他激素避孕药。本试验将由Dr. Tang作为R 01提交 在4年职业发展奖励期结束前提出申请。

ABSTRACT 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 scientists. 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 for a larger, multicenter clinical trial that will evaluate the risk for HIV acquisition among women using 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.