Sex, Aging and Antiretroviral Pharmacology

性别、衰老和抗逆转录病毒药理学

• 批准号: 7756666
• 负责人: KRISTINE B. PATTERSON
• 金额: $ 13.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7756666
• 关键词: Accounting; Affect; Age; Age-Years; Aging; Anti-Retroviral Agents; Area; Award; Biometry; Body Fluids; Chronic; Clinic; Clinical Pharmacology; Clinical Research; Clinical Sciences; Clinical Trials; Conduct Clinical Trials; Data; Data Collection; Development Plans; Discipline; Disease; Dose; Drug Exposure; Drug Kinetics; Environment; Estrogens; Evaluation; Foundations; Funding; Genital system; Goals; Guidelines; HIV; Hand; Highly Active Antiretroviral Therapy; Hormonal; Hormones; Immunology; In Vitro; Institution; Interdisciplinary Study; Intervention; Knowledge; Learning; Life; Liquid substance; Master of Science; Measures; Medicine; Menopause; Mentors; Mentorship; Methods; Modeling; North Carolina; Nucleosides; Pharmaceutical Preparations; Pharmacology; Pharmacy facility; Plasma; Population; Postmenopause; Premenopause; Prevention; Prevention strategy; Probability; Protease Inhibitor; Public Health; Public Health Schools; Recruitment Activity; Regimen; Research; Research Design; Research Methodology; Research Personnel; Reverse Transcriptase Inhibitors; Scientist; Sexual Transmission; Supplementation; Testing; Therapeutic Intervention; Time; Toxic effect; Training; Training Programs; United States; Universities; Viral; Viral Load result; Virus Shedding; Vision; Woman; Women Status; Women' s Health; antiretroviral therapy; base; career; career development; cohort; design; enzyme activity; genital secretion; interest; medical schools; non-nucleoside reverse transcriptase inhibitors; patient oriented; professor; programs; response; sex; skills; therapy development; treatment response; viral RNA; virology

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.

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NIH赞助的妇女健康跨学科研究职业建设计划(BIRCWH)进行正式的临床试验培训。职业目标：我的愿景是成为一名在临床药理学方面有专长的临床科学家，独立地在感染艾滋病毒的女性身上进行临床试验。职业发展计划：Patterson博士将接受临床药理学的正式培训，并通过临床科学硕士研究生项目加强她在定量方法和临床试验研究方面的基本知识。她将在进行研究计划中概述的临床研究和分析的同时接受实践培训。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为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HIV感染妇女生殖道抗逆转录病毒药物暴露情况。3)通过检测绝经后和绝经前HIV感染妇女在接受高效抗逆转录病毒治疗前后血浆和生殖道分泌物中HIV RNA的动态变化，确定和比较绝经后和绝经前HIV感染妇女的性传染性。研究方法：将在一组绝经后和绝经前感染艾滋病毒的妇女中，评估最常用的抗逆转录病毒药物的首剂、稳态和纵向药代动力学。将同时测量血浆和生殖器分泌物中的艾滋病毒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：这项研究将在北卡罗来纳大学的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的卫星诊所招募。北卡罗来纳大学医学院、药房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：两位主要导师在HIV(J.Eron)和HIV药理学(A.Kashuba)方面拥有专业知识，并将监督一支多产、成功的研究团队，他们在Patterson博士将要学习的学科中拥有坚实的基础，包括妇科学(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.Fiscus)和生物统计学(C.Moore)。相关性：通过这项培训计划和这项研究获得的知识将用于设计研究，通过补充外源性激素来调节感染性和治疗反应。