Sex, Aging and Antiretroviral Pharmacology

描述（由申请人提供）：候选人：Kristine B。Patterson博士是北卡罗来纳州大学（University of North Carolina）的医学助理教授，他已经开始通过NIH赞助的建立妇女健康跨学科研究职业（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临床科学家，拥有临床药理学方面的专业知识，独立进行艾滋病毒感染妇女的临床试验。职业发展计划：Patterson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增强她对定量方法和临床试验研究的基本知识。她将在进行研究计划中概述的临床研究和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，进一步向艾滋病毒感染妇女提供药物干预，以增加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感染妇女中抗逆转录病毒疗法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HIV感染妇女的生殖道抗逆转录病毒药物暴露。3)通过测量高效抗逆转录病毒治疗开始前后血浆和生殖道分泌物中的HIV RNA动态，确定并比较绝经后和绝经前HIV感染女性的性HIV感染性。研究方法：在绝经后和绝经前HIV感染女性队列中，将评估最常用抗逆转录病毒药物的首次给药、稳态和纵向药代动力学。同时测量血浆和生殖器分泌物HIV RNA。全身和生殖道病毒学应答将与抗逆转录病毒药物浓度相关，并相互关联。环境：本研究将在美国临床医学会的综合临床研究中心进行。受试者将从艾滋病病毒诊所和艾滋病病毒相关的卫星诊所招募。医学，药学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。导师制：两名主要导师具有艾滋病毒（J. Eron）和艾滋病毒药理学（A.卡舒巴），并将监督一个富有成效的，成功的调查小组，拥有强大的学科基础，将由帕特森博士学习，包括妇科（K。南达）和激素（鲁宾）的变化与衰老，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：通过本培训项目和本研究获得的知识将用于设计通过外源性激素补充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.