Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir

NCT04991402 | Completed

• 2 other identifiers: AAAT61121R01HD104599
• Study Type: observational
• Target: 1,920
• Locations: 1 country
• Sites: 2

Brief Summary

A total of 1900 pregnant women in the 1st trimester and their children will be enrolled and followed for two years (ORCHID study main cohort). As part of this, mother-infant pairs will be required to attend up to 10 study visits separate from routine clinic visits, these visits include 3 antenatal visits (less than or equal to 18, 24-28 and 32-36 weeks) and 16 postnatal visits (\<2 and 6 weeks, 3, 6, 12, 18, and 24 months). Participants will also be asked to engage in long-term follow-up, with visits occurring every 6 months through Month 60 (at 30, 36, 42, 48, 54, and 60 months). Measurements in mothers will include demographics and health status, HIV disease and ART use, intercurrent medical history including concomitant medication use, HIV viral load testing, ART adherence, HIV antibody testing in women without HIV; body composition, caloric intake, dysglycemia and insulin resistance (IR), lipid profiles, anthropometry, resting energy expenditure, hepatic steatosis, specimen collection (whole blood, plasma, serum, urine, placenta and breastmilk), systemic and adipose inflammation, as well as metabolites, lipid subspecies and eicosanoids. Measurements in infants will include uterine gestational age and fetal growth, as well as metabolites, lipid subspecies and eicosanoids, body composition, dysglycemia and IR, lipid profiles, anthropometry, feeding, specimen collection (cord blood, whole blood, plasma and serum) and intercurrent medical history including concomitant medication use. Additional data on maternal health in pregnancy and birth outcomes will be abstracted from medical records.

Conditions

HIV; Obesity; Obesity, Infant; Maternal Obesity During Childbirth; Maternal Obesity Complicating Pregnancy

Keywords

HIV; Dolutegravir; Metabolic health; Maternal obesity; Pregnancy

Outcome Measures

Primary Outcomes (8)

• Difference in excess gestational weight gain between pregnant women living with HIV and HIV negative pregnant women

  This is to measure the difference in gestational weight gain between pregnant women living with HIV and HIV negative pregnant women during pregnancy in kg. The women will be weighed by a scale at the study visit.

  <18 weeks (baseline), 32-34 weeks

• Difference in gestational weight gain between iDTG and cDTG pregnant women

  This is to measure the difference in gestational weight gain between pregnant women initiating DTG during pregnancy (iDTG) and pregnant women continuing DTG during pregnancy (cDTG) in kg. The mothers will be weighed by a scale at the study visit.

  <18 weeks (baseline), 32-34 weeks

• Change in adipose tissue mass compared between pregnant women living with HIV and HIV negative pregnant women

  Comparison of percent adipose tissue mass per week between pregnant women living with HIV and HIV negative pregnant women during pregnancy.

  <18 weeks (baseline), 32-34 weeks

• Change in adipose tissue mass compared between iDTG and cDTG mothers

  Comparison of percent adipose tissue mass per week between pregnant women initiating DTG during pregnancy (iDTG) and pregnant women continuing DTG during pregnancy (cDTG).

  <18 weeks (baseline), 32-34 weeks

• Differences in maternal metabolic health post-partum between mothers living with HIV and HIV negative mothers

  Adiposity will be measured as the main indicator of metabolic health. This outcome focuses on the comparison between mothers living with HIV and HIV negative mothers during pregnancy. Differences in adipose accrual and/or retention will calculated as the difference in adipose (% per week) between the timepoint in question and baseline.

  <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum

• Differences in maternal metabolic health post-partum between iDTG and cDTG mothers

  Adiposity will be measured as the main indicator of metabolic health. This outcome focuses on the comparison between mothers initiating DTG during pregnancy and mothers continuing DTG during pregnancy. Differences in adipose accrual and/or retention will calculated as the difference in adipose (% per week) between the timepoint in question and baseline.

  <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum

• Changes in adiposity in the child between HIV positive mothers and HIV negative mothers

  Adiposity will be measured as the main indicator of metabolic health. This outcome focuses on the comparison between children whose mothers are HIV positive and those whose mothers are HIV negative. Differences in adipose accrual and/or retention will calculated as the difference in adipose (% per week) between the timepoint in question and baseline.

  <2 weeks, up to 2 years of age

• Changes in adiposity in the child between iDTG and cDTG mothers

  Adiposity will be measured as the main indicator of metabolic health. This outcome focuses on the comparison between children whose mothers initiated DTG during pregnancy and those whose mothers continued DTG during pregnancy. Differences in adipose accrual and/or retention will calculated as the difference in adipose (% per week) between the timepoint in question and baseline.

  <2 weeks, up to 2 years of age

Secondary Outcomes (1)

• Changes in subcutaneous adipose tissue (SAT) function

  <18 weeks (baseline), 32-34 weeks antenatal, 24 months postpartum

Study Arms (3)

Pregnant women living with HIV initiating Dolutegravir (DTG) in pregnancy (iDTG)

Pregnant women living with HIV initiating DTG-based ART in pregnancy at the 1st visit

Device: Dolutegravir-based antiretroviral therapy

Pregnant women living with HIV already on DTG-based ART prior to pregnancy (cDTG)

Pregnant women living with HIV already on DTG-based ART prior to enrollment and continuing DTG use through pregnancy

Device: Dolutegravir-based antiretroviral therapy

HIV uninfected pregnant women

Pregnant women not living with HIV

Interventions

Dolutegravir-based antiretroviral therapy DEVICE

This study focuses on the impact of Dolutegravir (DTG)-based antiretroviral therapy (ART) on metabolic health of women and children in pregnancy, delivery and beyond. In order to understand the potential adverse effects of DTG, pregnant women living with HIV- both those initialing DTG-based ART in pregnancy as well as those who were established on DTG-based ART prior to pregnancy, will be less than or equal to 18 weeks' gestation at enrollment to allow for detection of metabolic abnormalities as they begin to develop during the course of pregnancy. This is considered standard of care.

Pregnant women living with HIV already on DTG-based ART prior to pregnancy (cDTG); Pregnant women living with HIV initiating Dolutegravir (DTG) in pregnancy (iDTG)

Eligibility Criteria

• Age: 16 Years+
• Gender Eligibility Details: Participants are pregnant women- some living with HIV and some HIV uninfected.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The investigator will recruit up to 1900 pregnant women at their 1st antenatal clinic visit. Enrollment will be distributed across three main exposure categories by HIV status and Dolutegravir use: pregnant women living with HIV and initiating DTG-based ART in pregnancy (iDTG); pregnant women living with HIV already on DTG-based regimen prior to pregnancy and continuing DTG through pregnancy (cDTG); and pregnant women without HIV infection.

You may qualify if:

• For All Women:
• Confirmed pregnancy based on urine pregnancy test with viable gestation ≤ 18 weeks and 6 days by ultrasound
• Age 16 years or older
• No stated intention to relocate permanently outside of Cape Town through 2 years postpartum
• For Women Living with HIV (WLHIV):
• Confirmed HIV infection based on medical record review and/or HIV antibody testing during antenatal care
• For WLHIV continuing DTG in pregnancy (cDTG):
• Confirmed use of tenofovir 300mg + lamivudine 300mg/emtricitabine 200mg + dolutegravir 50mg (TLD) on the day of assessment
• For WLHIV initiating DTG in pregnancy (iDTG):
• Planned initiation of TLD on the day of assessment or within 1 week thereafter, including women switching from efavirenz-based regimen
• For women without HIV (HIV-):
• Confirmed HIV status by HIV antibody testing during antenatal care

You may not qualify if:

• In the opinion of the investigator, unable to provide informed consent due to mental or physical condition
• In the opinion of the investigator, unable to undertake BodPod assessment due to mental (eg, active psychosis or severe claustrophobia) or physical condition (eg, weight \>250 kg).
• Currently being treated for any form of diabetes mellitus or hypertensive disorder based on participant self-report and medical record review

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Northwestern University: collaborator
• University of Cape Town: collaborator
• University of Hawaii: collaborator
• Tufts University: collaborator
• Albert Einstein College of Medicine: collaborator
• Columbia University: lead

Study Sites (2)

Gugulethu Community Health Center

Cape Town, South Africa

Location

Mitchell's Plain Community Health Center

Cape Town, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cord blood, whole blood, plasma and serum, breastmilk, urine, adipose tissue (substudy participants only)

MeSH Terms

Conditions

Obesity; Pediatric Obesity; Pregnancy in Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Elaine J. Abrams, MD

  ICAP at Columbia University

  PRINCIPAL INVESTIGATOR

• Jennifer Jao, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Director

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: August 5, 2021
• Study Start: September 21, 2021
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: De-identified datasets will be available in DASH no later than 3 years after the completion of baseline study visits.
• Access Criteria: When the study is completed, access to study data will be provided through NICHD's DASH repository. Researchers seeking to access data stored in DASH will need to follow pre-specified requirements around data access requests.

Locations

ZA (2)