Sex, Aging and Antiretroviral Pharmacology

描述（由申请人提供）：候选人：Kristine B. Patterson，医学博士，北卡罗来纳大学（UNC）医学助理教授，已经开始通过美国国立卫生研究院资助的妇女健康跨学科研究事业（BIRCWH）计划进行正式的临床试验培训。职业目标：我的愿景是成为一名具有临床药理学专业知识的临床科学家，在感染艾滋病毒的妇女中独立进行临床试验。职业发展规划：帕特森博士将获得临床药理学方面的正式培训，并通过临床科学硕士研究生课程提高她在定量方法和临床试验研究方面的基本知识。她将在进行临床研究和研究计划中概述的分析时获得实践培训。近期目标：获得临床药理学和临床试验的设计、实施、数据收集和分析方面的专业知识。长期目标：利用这些技能进一步向感染艾滋病毒的妇女提供药物干预措施，以提高治疗效果并降低传染性。具体目的：1)测量和比较绝经后和绝经前HIV感染妇女抗逆转录病毒治疗的稳态血浆药代动力学。2)纵向量化和比较绝经后和绝经前艾滋病毒感染妇女生殖道抗逆转录病毒药物暴露情况。3)通过测定高活性抗逆转录病毒治疗前后血浆和生殖道分泌物中的HIV RNA动态，确定和比较绝经后和绝经前HIV感染妇女的性HIV感染情况。研究方法：将在绝经后和绝经前感染艾滋病毒的妇女队列中评估最常用的抗逆转录病毒药物的首次剂量、稳态和纵向药代动力学。同时测定血浆和生殖器分泌物的HIV RNA。全身和生殖道病毒学反应将与抗逆转录病毒浓度相关，并相互关联。环境：本研究将在北卡罗来纳大学普通临床研究中心进行。受试者将从UNC HIV诊所和UNC相关的卫星诊所招募。北卡罗来纳大学医学院、药学院和公共卫生学院将为帕特森博士的培训提供丰富的学习环境。导师：两位主要导师拥有HIV （J. Eron）和HIV药理学（a . Kashuba）方面的专业知识，并将监督一个富有成效、成功的研究团队，该团队在帕特森博士要学习的学科中拥有强大的基础，包括妇科（K. Nanda）和荷尔蒙（J. Rubin）与衰老相关的变化、免疫学（D. Margolis）、生殖道病毒学（S. fisus）和生物统计学（C. Moore）。相关性：通过本培训计划和本研究获得的知识将用于设计通过补充外源性激素调节传染性和治疗反应的研究。

DESCRIPTION (provided by applicant): Candidate: Kristine B. Patterson, MD, Assistant Professor of Medicine at the University of North Carolina (UNC) has begun formal clinical trial training through the NIH-sponsored Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program. Career Goals: My vision is to be a clinician scientist with expertise in clinical pharmacology who is independently conducting clinical trials in HIV-infected women. Career Development Plans: Dr. Patterson will obtain formal training in clinical pharmacology and enhance her basic knowledge of quantitative methods and clinical trials research conduct through the Master of Science in Clinical Science graduate program. She will obtain hands on training while performing the clinical studies and analyses outlined in the research plan. Immediate Objective: To acquire expertise in clinical pharmacology and the design, implementation, data collection, and analysis of clinical trials. Long-term Objective: To use these skills to further the pharmacologic interventions available to HIV-infected women to increase treatment responses and to decrease infectiousness. Specific Aims: 1) To measure and compare steady state blood plasma pharmacokinetics of antiretroviral therapies in post- and pre-menopausal HIV- infected women. 2) To longitudinally quantify and compare genital tract antiretroviral drug exposure in post- and pre-menopausal HIV-infected women. 3) To determine and compare sexual HIV infectivity in post- and pre-menopausal HIV-infected women by measuring HIV RNA dynamics in blood plasma and genital tract secretions before and after the initiation of highly active antiretroviral therapy. Research Methods: First- dose, steady-state and longitudinal pharmacokinetics of the most commonly prescribed antiretroviral agents will be assessed in the systemic and genital tract compartments in a cohort of post- and pre-menopausal HIV-infected women. Concurrent blood plasma and genital secretions HIV RNA will be measured. Systemic and genital tract virologic responses will be correlated with antiretroviral concentrations and with each other. Environment: This study will take place at UNC's General Clinical Research Center. Subjects will be recruited from the UNC HIV Clinic and UNC's associated satellite clinics. The UNC Schools of Medicine, Pharmacy and Public Health will provide a rich learning environment for Dr. Patterson's training. Mentorship: The two primary mentors have expertise in HIV (J. Eron) and HIV pharmacology (A. Kashuba) and will oversee a team of productive, successful investigators that boasts strong foundations in the disciplines to be learned by Dr. Patterson, including gynecological (K. Nanda) and hormonal (J. Rubin) changes associated with aging, immunology (D. Margolis), genital tract virology (S. Fiscus) and biostatistics (C. Moore). Relevance: The knowledge gained through this training program and from this study will be used to design studies that modulate infectivity and treatment responses through exogenous hormone supplementation.