Metabolomic predictors of weight gain during pregnancy and the postpartum period in South African women living with HIV

PROJECT SUMMARY People living with HIV (PLHIV) have a persistently reduced lifespan compared to their negative counterparts due to increased risk of metabolic co-morbidities such as diabetes and cardiovascular diseases. Among women of reproductive potential, gestational weight gain (GWG) and postpartum weight retention (PPWR) are

known contributors to the onset of these metabolic co-morbidities. Early detection of pregnant women at risk of excessive GWG and PPWR can enable early interventions that will help minimize the occurrence of these co- morbidities in women living with HIV (WLHIV). The overarching goal of this proposal is to identify urine

metabolites that are predictive of excessive GWG and PPWR in WLHIV. Candidate: Dr. Madlala is a Physiologist/Epidemiologist with training in molecular sciences, quantitative research methods and experience in field research implementation in South Africa. She is applying for a five-year Fogarty Emerging Global

Leader Award to obtain the additional training, mentorship and experience required to become a leading independent investigator capable of obtaining R-series funding. Mentoring: She has assembled an exceptional multidisciplinary team with extensive expertise in metabolic outcomes of HIV research in sub-

Saharan Africa. Drs. Myer (University of Cape Town, (UCT)) and Jao (Northwestern University) will serve as primary mentors providing complementary expertise on metabolic outcomes of WLHIV and clinical use of biomarkers. Dr. Goedecke (UCT, SAMRC), co-mentor, is a Physiologist with expertise in mechanistic science

research. Dr. Kurland (Albert Einstein: expertise in metabolomics laboratory technique) and Dr. Balmert (Northwestern University: expertise in ‘omics’ data handling and pathway analysis) will serve as scientific advisors in these areas. Training: Specific training in biomarker discovery study design, ‘big’ data statistical

analysis and metabolic pathway elucidation – will be achieved through intensive mentored training and formal coursework. This, combined with the experience gained through implementing her research aims, will establish Dr. Madlala’s independent research career investigating early biomarkers of adverse metabolic health in

PLHIV. Research: The specific aims of this research are to: 1) assess whether HIV infection is associated with differences in urine metabolite species during the first trimester of pregnancy, 2) develop risk prediction models for (i) GWG, (ii) PPWR and (iii) postpartum adiposity using metabolites and clinical variables, and 3) elucidate

the metabolic pathways of (i) GWG, (ii) PPWR and (iii) adiposity by applying pathway/network analysis to the prognostic metabolites identified. The results of this study will inform the development of urinary metabolite- based screening tool for adverse weight outcomes aimed at minimizing metabolic co-morbidities in pregnant

and postpartum WLHIV. They will provide preliminary data needed to apply for an R01 to conduct a large scale study to rigorously examine predictive biomarker profile for metabolically healthy (without co-morbidities) versus unhealthy (with co-morbidities) excessive GWG and PPWR.