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Principal Investigator: AHIZECHUKWU C. EKE
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $170,612
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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.
Terms: <0-11 years old><21+ years old><2nd trimester><3rd trimester><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adherence><Adult><Adult Human><Adverse effects><Anti-Retroviral Agents><Baltimore><Benchmarking><Best Practice Analysis><Biometrics><Biometry><Biostatistics><Blood><Blood Glucose><Blood Plasma><Blood Reticuloendothelial System><Blood Serum><Blood Sugar><Cells Placenta-Tissue><Child><Child Youth><Children (0-21)><Clinical Pharmacology><Clinical Trials Network><Cohort Studies><Collaborations><Concurrent Studies><Cytochrome P-450><Cytochrome P-450 Enzyme System><Cytochrome P450><Cytochrome P450 Family Gene><Data><Data Analyses><Data Analysis><Data Bases><Databases><Decision Making><Development><Development Plans><Diphosphates><Dose><Drug Kinetics><Drug Modelings><Drug Precursors><Drug Therapy><Drug or chemical Tissue Distribution><Drug usage><Drugs><Dryness><EPH Gestosis><Enrollment><Environment><Enzyme Gene><Enzymes><Exposure to><FDA approved><Female Health><Fetus><Fumarates><Funding><Future><GNT1><Gestation><Gestational Diabetes><Gestational Diabetes Mellitus><Glucuronic Transferase><Glucuronosyltransferase><Glucuronyltransferase><Goals><HDL><HDL Lipoproteins><HIV><Hair><Health><Heavy Lipoproteins><High Density Lipoproteins><High density lipoprotein><Hospitals><Human Immunodeficiency Viruses><Hypertension><IMPAACT><In Vitro><Institution><International Maternal Pediatric Adolescent AIDS Clinical Trials><International Maternal Pediatric Adolescent HIV/AIDS Clinical Trials><Investigation><Investigators><Knowledge><LAV-HTLV-III><Last Trimester><Lead><Logistic Regressions><Lymphadenopathy-Associated Virus><Maryland><Maternal-fetal medicine><Measures><Medication><Mentors><Mentorship><Metabolic><Metabolic syndrome><Midtrimester><Modeling><Modification><Mothers><NIH><National Institutes of Health><Normal Placentoma><P450><PBMC><PBPK><Participant><Pb element><Perinatal Epidemiology><Peripheral Blood Mononuclear Cell><Pharmaceutical Epidemiology><Pharmaceutical Preparations><Pharmacoepidemiology><Pharmacokinetics><Pharmacology><Pharmacotherapy><Phase><Physicians><Physiology><Placenta><Placenta Embryonic Tissue><Placentome><Plasma><Plasma Serum><Population><Post-partum Women><Postpartum Period><Postpartum Women><Pre-Eclampsia><Preeclampsia><Pregnancy><Pregnancy Toxemias><Pregnancy Trimesters><Pregnancy-Induced Diabetes><Pregnant Women><Premature Birth><Prematurely delivering><Preterm Birth><Prevention><Pro-Drugs><Prodrugs><Prospective, cohort study><Proteinuria-Edema-Hypertension Gestosis><PubMed><Publications><Pyrophosphates><Research><Research Design><Research Personnel><Researchers><Reticuloendothelial System, Serum, Plasma><Risk><Safety><Scientific Publication><Scientist><Second Pregnancy Trimester><Second Trimester><Serum><Special Population><Spottings><Study Type><Syndrome><Techniques><Tenofovir><Testing><Therapeutic><Third Pregnancy Trimester><Third Trimester><Tissue Distribution><Training><Transmission><Triacylglycerol><Triglycerides><UDP Glucuronosyltransferase><UDP Glucuronyl Transferase><UDP glycosyltransferase 1 family, polypeptide A1 Gene><UDP glycosyltransferase gene 1><UGT1><UGT1A><UGT1A1><UGT1A1 gene><UGT1A5><United States National Institutes of Health><Universities><Uridine Diphosphate><Uridine Pyrophosphate><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Viread><Virus-HIV><Weight Gain><Weight Increase><Woman><Women's Health><Work><adulthood><alpha-Lipoproteins><analytical method><anti-retroviral><anti-viral efficacy><antiretroviral therapy><antiretroviral treatment><benchmark><body weight gain><body weight increase><career><career development><cohort><data base><data interpretation><developmental><drug adherence><drug compliance><drug epidemiology><drug safety><drug treatment><drug use><drug/agent><enroll><expectant mother><expecting mother><fetal><fetal drug exposure><gestational drug exposure><heavy metal Pb><heavy metal lead><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><improved><in silico><in vivo><innovate><innovation><innovative><kids><medication adherence><medication compliance><medication safety><member><novel><perinatal HIV><pharmaceutical safety><pharmacoepidemiologic><pharmacoepidemiological><pharmacokinetic model><pharmacometrics><physiologically based pharmacokinetics><post-partum><pre-eclamptic><pregnancy diabetes><pregnancy toxemia/hypertension><pregnant mothers><premature childbirth><premature delivery><prenatal drug exposure><prenatally drug exposed><preterm delivery><prevent><preventing><prospective><safety assessment><secondary analysis><skills><study design><tool><transmission process><viral resistance><virus resistance><waist circumference><wt gain><youngster>