An observational cohort study to investigate the impact of dolutegravir in pregnancy and its obesogenic effects on the metabolic health of women living with HIV and their children: Study protocol

Elaine J. Abrams*, Jennifer Jao, Hlengiwe P. Madlala, Allison Zerbe, Patrick Catalano, Mariana Gerschenson, Julia H. Goedecke, Yolanda Gomba, Jami Josefson, Irwin J. Kurland, Justine Legbedze, Grace A. McComsey, Sandisiwe Matyesini, Elton Mukonda, Daniel Robinson, Landon Myer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization’s preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRi-gins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. Materials & methods ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT 04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. Discussion ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.

Original languageEnglish (US)
Article numbere0307296
JournalPloS one
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2024

Funding

Research reported in this publication is supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R01HD104599 to EJA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank the ongoing commitment of the participants, staff members at the various recruitment sites and study staff members at the Gugulethu Community Health Center.

ASJC Scopus subject areas

  • General

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