Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir

NCT ID: NCT04991402

Last Updated: 2026-02-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1920 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-09-21
• Study Completion Date: 2025-05-30

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.

Detailed Description

Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up as part of the preferred 1st-line ART regimen. However, DTG has recently been implicated as an obesogen that is associated with increased weight and adipose tissue gain compared to other antiretroviral agents. Obesity in pregnancy is associated with poor health outcomes for both mother and child as pregnancy is a critical period during which exposures leading to alterations in metabolic health may influence not only long-term maternal health but also fetal, neonatal, and ultimately child health. To address the gap of knowledge on the obesogenic effects of DTG in pregnant women living with HIV (WLHIV) and their children, this prospective cohort study will investigate the impact of DTG in pregnancy and its obesogenic effects on the metabolic health of WLHIV and their children, compared to women without HIV and their children. Up to 1900 pregnant women will be enrolled and followed to delivery and then as mother-infant pairs through 5 years postpartum (ORCHID study main cohort).

Additionally, a nested cohort study will be conducted and enroll a subset of 108 pregnant women who are currently being followed as part of the parent ORCHID study's main cohort. This substudy will explore the associations of DTG (initiating and continuing DTG use during pregnancy) with longitudinal perturbations in subcutaneous adipose tissue (SAT) function and changes in weight and adipose tissue mass in pregnancy through 2 years postpartum in WLHIV using a comparison group of HIV-seronegative women. They will been seen at up to 3 different time points (up to 2 visits during pregnancy and 1 visit postpartum) separate from the parent study to undergo a fat biopsy procedure to extract SAT samples.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Dolutegravir-based antiretroviral therapy

Intervention Type: 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 already on DTG-based ART prior to enrollment and continuing DTG use through pregnancy

Dolutegravir-based antiretroviral therapy

Intervention Type: 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.

HIV uninfected pregnant women

Pregnant women not living with HIV

No interventions assigned to this group

Interventions

Dolutegravir-based antiretroviral therapy

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Northwestern University

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Hawaii

OTHER

Sponsor Role: collaborator

Tufts University

OTHER

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Elaine J. Abrams, MD

Senior Research Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elaine J. Abrams, MD

Role: PRINCIPAL_INVESTIGATOR

ICAP at Columbia University

Jennifer Jao, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Gugulethu Community Health Center

Cape Town, , South Africa

Mitchell's Plain Community Health Center

Cape Town, , South Africa

Countries

South Africa

Other Identifiers

1R01HD104599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAT6112

Identifier Type: -

Identifier Source: org_study_id