Sex, Aging and Antiretroviral Pharmacology

描述（由申请人提供）：候选人：北卡罗来纳大学 (UNC) 医学助理教授克里斯汀·B·帕特森 (Kristine B. Patterson) 医学博士已通过 NIH 资助的建立女性健康跨学科研究职业 (BIRCWH) 计划开始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，独立对艾滋病毒感染女性进行临床试验。职业发展计划：帕特森博士将通过临床科学研究理学硕士课程获得临床药理学的正式培训，并增强定量方法和临床试验研究行为的基础知识。她将在进行研究计划中概述的临床研究和分析的同时获得实践培训。近期目标：获得临床药理学以及临床试验的设计、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对艾滋病毒感染妇女进行药物干预，以提高治疗反应并降低传染性。具体目标： 1) 测量和比较绝经后和绝经前 HIV 感染女性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的生殖道抗逆转录病毒药物暴露情况。 3) 通过测量开始高效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 感染女性的性 HIV 感染情况。研究方法：将在一组绝经后和绝经前 HIV 感染女性的全身和生殖道区室中评估最常用抗逆转录病毒药物的首剂、稳态和纵向药代动力学。同时检测血浆和生殖器分泌物中的 HIV RNA。全身和生殖道病毒学反应将与抗逆转录病毒浓度以及彼此之间相关。环境：这项研究将在北卡罗来纳大学普通临床研究中心进行。受试者将从北卡罗来纳大学艾滋病毒诊所和北卡罗来纳大学相关卫星诊所招募。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。指导：两位主要导师拥有艾滋病毒 (J. Eron) 和艾滋病毒药理学 (A. Kashuba) 方面的专业知识，并将监督一支富有成效、成功的研究人员团队，这些研究人员在帕特森博士将要学习的学科方面拥有坚实的基础，包括与衰老相关的妇科 (K. Nanda) 和激素 (J. Rubin) 变化、免疫学 (D. Margolis)、生殖道病毒学 (S. Fiscus) 和生物统计学（C.摩尔）。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激素来调节感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.