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

简介（由申请人提供）：候选人：Susan Graham，医学博士，公共卫生硕士，华盛顿大学（UW）传染病高级研究员，接受内科和公共卫生培训，拥有4年以上的国际研究经验。在她的研究期间，她研究了肯尼亚接受抗逆转录病毒治疗的妇女中HIV-1生殖道脱落的情况。她的近期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研究者，领导一个研究小组，在资源有限的情况下研究艾滋病毒感染的临床流行病学、预防和治疗。环境：华盛顿大学拥有艾滋病研究中心、国际艾滋病研究和培训项目以及优秀的研究生水平培训项目，是国际艾滋病毒/艾滋病研究职业发展的理想场所。格雷厄姆博士将由她现在的导师。King Holmes和Scott McClelland，并将与Julie Overbaugh博士的HIV-1病毒学实验室合作。蒙巴萨现场提供了行政基础设施、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。Graham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：在资源有限的环境中，一线抗逆转录病毒治疗失败的患者选择有限，并可能传播耐药病毒。这项前瞻性队列研究将评估二线治疗在血浆和生殖道分泌物中抑制HIV-1复制的有效性。我们将评估一线治疗失败后的耐药性、二线治疗后的病毒抑制以及HIV-1生殖器持续脱落的相关因素。这项研究的独特之处包括关注传播风险高的妇女，从两个正在进行的具有一线治疗史数据的队列中入组，以及我们小组在HIV-1生殖器脱落研究方面的丰富研究经验。相关性：我们建议研究开始二线抗逆转录病毒治疗的高危妇女血液和生殖器分泌物中的HIV-1。随着艾滋病毒治疗的扩大，耐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..