# Integrated proteomic and metabolomic biomarker profiling for understanding metabolic syndrome in pregnant women living with HIV on Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir (TLD)

> **NIH NIH DP1** · JOHNS HOPKINS UNIVERSITY · 2024 · $573,125

## Abstract

PROJECT ABSTRACT/SUMMARY
Effective HIV treatment during pregnancy is critically important, both for the health of women living with HIV
(PWHIV) and for prevention of perinatal HIV transmission. In the United States, Nigeria, and globally,
Dolutegravir (DTG)- based antiretroviral therapy (ART) is being expanded as part of the preferred 1st-line ART
regimen, but emerging data show that DTG-based regimens are associated with excessive weight gain,
treatment-emergent obesity, and metabolic dysfunction in PWHIV. Excessive weight gain and metabolic
syndrome are critical during pregnancy because they increase the risk for pregnancy-related complications, such
as preterm birth, pre-eclampsia, gestational diabetes, fetal obesity, macrosomia, low birth weight, Cesarean
delivery, and neonatal intensive care unit admissions. Yet, the mechanisms by which DTG-based ART-cause
weight gain and metabolic syndrome in PWHIV are poorly understood, limiting our ability to fully deploy DTG-
based ART in this special population. To address this goal, we will leverage NIH infrastructure to conduct a
prospective cohort study at 4 sites in two countries (US and Nigeria). Within this cohort, we will first identify cases
of metabolic syndrome by examining the association between DTG-based ART regimens and metabolic
syndrome risk using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)
criteria for pregnant and postpartum women living with HIV, and cohort-specific percentiles for waist
circumference, systolic blood pressure, and serum glucose for their offspring. Subsequently, among PWHIV
diagnosed with metabolic syndrome (compared to controls), we will apply advanced integrated proteomic and
metabolomic targeted profiling techniques to measure maternal proteins and metabolites (during pregnancy and
postpartum) and umbilical cord blood proteins and metabolites to understand whether signature clusters of
proteins and metabolites differ between PWHIV diagnosed with metabolic syndrome (compared to selected
controls), and if any signature clusters are associated with adverse maternal and child metabolic health.
Biomarkers identified through integrated profiling would enhance the synergistic power of these ‘omics’
approaches to enable early detection of metabolic syndrome (even before clinical symptoms manifest), provide
insights into treatment efficacy and potential adverse effects, and contribute to the development of personalized
medicine strategies for PWHIV to guide the selection of interventions and therapies tailored to specific metabolite
profiles in clinical practice.

## Key facts

- **NIH application ID:** 10917867
- **Project number:** 1DP1HD115433-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** AHIZECHUKWU C. EKE
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,125
- **Award type:** 1
- **Project period:** 2024-08-05 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917867

## Citation

> US National Institutes of Health, RePORTER application 10917867, Integrated proteomic and metabolomic biomarker profiling for understanding metabolic syndrome in pregnant women living with HIV on Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir (TLD) (1DP1HD115433-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10917867. Licensed CC0.

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