Understanding Medication Adherence Benchmarks, Safety and Pharmacometrics of Novel Antiretrovirals in Pregnant Women Living with HIV.

了解感染艾滋病毒孕妇的新型抗逆转录病毒药物的用药依从性基准、安全性和药理学。

• 批准号: 10158829
• 负责人: AHIZECHUKWU C. EKE
• 金额: $ 17.15万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-25 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10158829
• 关键词: AIDS prevention; Adherence; Adult; Adverse effects; Anti-Retroviral Agents; Baltimore; Benchmarking; Biometry; Blood; Blood Glucose; Child; Clinical Pharmacology; Clinical Trials Network; Cohort Studies; Collaborations; Cytochrome P450; Data; Data Analyses; Databases; Decision Making; Development; Development Plans; Diphosphates; Dose; Drug Kinetics; Drug Modelings; Drug or chemical Tissue Distribution; Drug usage; Enrollment; Environment; Enzymes; Exposure to; FDA approved; Fetus; Fumarates; Funding; Future; Gestational Diabetes; Goals; HIV; Hair; Health; High Density Lipoproteins; Hospitals; Hypertension; In Vitro; Institution; International Maternal Pediatric Adolescent AIDS Clinical Trials; Investigation; Knowledge; Lead; Logistic Regressions; Maryland; Maternal-fetal medicine; Measures; Mentors; Mentorship; Metabolic; Metabolic syndrome; Modeling; Modification; Mothers; Participant; Perinatal Epidemiology; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Pharmacotherapy; Phase; Physicians; Physiological; Physiology; Plasma; Population; Postpartum Period; Postpartum Women; Pre-Eclampsia; Pregnancy; Pregnancy Trimesters; Pregnant Women; Premature Birth; Prodrugs; Prospective cohort study; PubMed; Publications; Research; Research Design; Research Personnel; Risk; Safety; Scientist; Second Pregnancy Trimester; Serum; Spottings; Syndrome; Techniques; Tenofovir; Testing; Therapeutic; Third Pregnancy Trimester; Training; Transferase; Triglycerides; UGT1A1 gene; United States National Institutes of Health; Universities; Uridine Diphosphate; Weight Gain; Woman; Women' s Health; Work; analytical method; anti-viral efficacy; antiretroviral therapy; base; career; career development; cohort; fetal; fetal drug exposure; improved; in silico; in vivo; innovation; medication compliance; medication safety; member; named group; novel; perinatal HIV; pharmacokinetic model; pharmacometrics; physiologically based pharmacokinetics; pregnant; prevent; prospective; safety assessment; secondary analysis; skills; tool; transmission process; viral resistance; waist circumference

PROJECT SUMMARY/ABSTRACT Background: Effective HIV treatment during pregnancy is critically important, both for the health of women living with HIV (WLHIV) and for prevention of perinatal HIV transmission. There are knowledge gaps though, that limit our ability to deploy new effective antiretroviral therapy agents in this special population. The proposed mentored K23 application is an investigation led by Dr. Ahizechukwu Eke on the effects of pregnancy on the pharmacology of new HIV drugs, including effects on adherence measures, and on these drugs’ safety in pregnant women. Candidate: Dr. Ahizechukwu Eke is a Maternal Fetal Medicine and Clinical Pharmacology-trained Physician-Scientist who has spent the past 4 years conducting research on the clinical pharmacology of drugs in pregnant women. He helped establish a cohort of pregnant women living with HIV (WLHIV) at Johns Hopkins, developed strong scientific collaborations with pharmacometricians and scientists through the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, and authored 65 PubMed-cited publications related to his research. Research: In Aim 1, among pregnant WLHIV taking tenofovir alafenamide (TAF), Dr Eke will characterize the pharmacokinetics (PK) of tenofovir (TFV) and its active form (intracellular tenofovir diphosphate – TFV-DP), and establish PK adherence benchmarks in pregnancy using PK modeling. Aim 2 examines pregnancy-specific safety of TAF by exploring its association with development of metabolic syndrome in pregnant WLHIV, and Aim 3 uses physiologically based PK (PBPK) modeling to predict maternal and fetal bictegravir and doravirine concentrations, confirming results in pregnant WLHIV enrolling in a prospective multi-center PK cohort study (IMPAACT 2026). Career Development Plan: Dr. Eke’s long term goal is to become an independent physician-scientist focused on HIV therapeutics in pregnant women. His short term goals and the focus of this K23 application, are to fill the gaps in his research skillset that he and his mentoring team have identified by focusing on these objectives:1) To grow his skills in advanced PK modeling, including models that incorporate adherence, and pharmacometrics; 2) to gain skills in safety assessments in pregnancy via data analysis and focused coursework on longitudinal data analysis and pharmaco-epidemiology study design, and; 3) to understand how PBPK models are developed and can be used to facilitate drug and dose selection for pregnant women. Dr Eke plans to achieve these objectives by working with mentors with expertise directly relevant to his career goals: Dr Craig Hendrix and Kelly Dooley (Clinical Pharmacology and HIV); Dr Jeanne Sheffield (Perinatal Epidemiology, Maternal Fetal Medicine, and HIV); and Dr Joga Gobburu (Pharmacometrics, PBPK modeling). Environment: The institutional environments at both Johns Hopkins (Hendrix, Dooley and Sheffield) and the Pharmacometrics Division at the University of Maryland (Gobburu) are ideal for training and research in the pharmacology of drugs in pregnancy. The long-standing collaboration between these institutions and the strong collaboration with members of IMPAACT will provide Dr. Eke with strong mentorship to advance his research career.

项目总结/文摘