Genital HIV-1 Shedding among Women Starting Second-Line Antiretroviral Therapy

应聘者：苏珊·格雷厄姆，医学博士，公共卫生硕士，华盛顿大学传染病高级研究员，接受过内科和公共卫生方面的培训，并有4年以上的国际研究经验。在她担任研究员期间，她研究了肯尼亚接受抗逆转录病毒治疗的妇女中艾滋病毒-1生殖道脱落的情况。她近期的目标是完成几项关于抗逆转录病毒治疗对生殖道脱落影响的前瞻性队列研究，并完成流行病学博士学位。她的长期目标是成为一名独立的调查员，领导一个研究团队，在资源有限的情况下对艾滋病毒感染的临床流行病学、预防和治疗进行研究。环境：威斯康星大学拥有艾滋病研究中心、国际艾滋病研究和培训计划以及优秀的研究生水平培训计划，非常适合在国际艾滋病毒/艾滋病研究领域开展职业发展。格雷厄姆博士将由她目前的导师金·霍姆斯博士和斯科特·麦克莱兰博士监督，并将与朱莉·奥博夫博士的HIV-1病毒学实验室合作。蒙巴萨现场提供行政基础设施、强有力的实验室支持，以及成功开展许多大型流行病学研究的记录。格雷厄姆博士在蒙巴萨北部的一家新诊所建立的HIV-1血清阳性患者队列为未来项目的发展提供了充足的机会。研究：在资源有限的情况下，一线抗逆转录病毒治疗失败的患者选择有限，可能会传播抗药性病毒。这项拟议的前瞻性队列研究将评估二线治疗在抑制血浆和生殖道分泌物中HIV-1复制方面的有效性。我们将评估一线治疗失败时的耐药性，随后二线治疗的病毒抑制，以及持续的HIV-1生殖器脱落的相关性。这项研究的独特之处包括对传播高危妇女的关注，从两个正在进行的队列中招募一线治疗史数据，以及我们小组在艾滋病毒-1生殖器脱落研究方面的广泛研究经验。相关性：我们建议研究开始二线抗逆转录病毒治疗的高危女性血液和生殖器分泌物中的HIV-1。随着艾滋病毒治疗的规模扩大，抗药性研究和二线治疗的成功至关重要，格雷厄姆博士准备在这一领域做出重要贡献。

DESCRIPTION (provided by applicant): Candidate: Susan Graham, MD, MPH, is a Senior Fellow in Infectious Diseases at the University of Washington (UW) with training in internal medicine and public health and over 4 years of experience in international research. During her fellowship, she has studied HIV-1 genital tract shedding among antiretroviral-treated women in Kenya. Her immediate goals are to complete several prospective cohort studies of the impact of antiretroviral therapy on genital tract shedding, and to complete a doctoral degree in epidemiology. Her long-term objective is to become an independent investigator, leading a research team on the clinical epidemiology, prevention, and treatment of HIV infection in resource-limited settings. Environment: The UW, with its Center for AIDS Research, International AIDS Research and Training Program, and outstanding graduate-level training programs, is ideal for career development in international HIV/AIDS research. Dr. Graham will be supervised by her current mentors, Drs. King Holmes and Scott McClelland, and will collaborate with Dr. Julie Overbaugh's HIV-1 virology laboratory. The Mombasa field site provides administrative infrastructure, strong laboratory support, and a record of having successfully conducted many large epidemiologic studies. A cohort of HIV-1 seropositive patients established by Dr. Graham in a new clinic north of Mombasa provides ample opportunities for development of future projects. Research: In resource-limited settings, patients who fail first-line antiretroviral therapy have limited options and may transmit drug-resistant virus. The proposed prospective cohort study will evaluate the effectiveness of second-line therapy at suppressing HIV-1 replication in both plasma and genital tract secretions. We will evaluate resistance at failure of first-line therapy, subsequent viral suppression by second-line therapy, and correlates of continued HIV-1 genital shedding. Unique aspects of this study include the focus on women at high risk for transmission, enrollment from two ongoing cohorts with data on first-line therapy history, and our group's extensive research experience in studies of HIV-1 genital shedding. Relevance: We propose to study HIV-1 in blood and genital secretions of high-risk women starting second-line antiretroviral therapy. As HIV therapy is scaled up, research on drug resistance and the success of second-line treatment is crucial, and Dr. Graham is poised to make an important contribution in this area..