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Completed

NCT Number: NCT04991402

Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir

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.

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Key information

Conditions

HIV Body Weight Female Urogenital Diseases and Pregnancy Complications Maternal Obesity Complicating Pregnancy Maternal Obesity During Childbirth Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Infant Overnutrition Overweight Pathological Conditions, Signs and Symptoms Pediatric Obesity Pregnancy Complications Pregnancy in Obesity Signs and Symptoms Urogenital Diseases

Age range

16 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Gugulethu Community Health Center, Cape Town, South Africa

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

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

    Time frame: <18 weeks (baseline), 32-34 weeks

    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.

  2. Difference in gestational weight gain between iDTG and cDTG pregnant women

    Time frame: <18 weeks (baseline), 32-34 weeks

    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.

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

    Time frame: <18 weeks (baseline), 32-34 weeks

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

  4. Change in adipose tissue mass compared between iDTG and cDTG mothers

    Time frame: <18 weeks (baseline), 32-34 weeks

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

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

    Time frame: <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum

    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.

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

    Time frame: <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum

    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.

  7. Changes in adiposity in the child between HIV positive mothers and HIV negative mothers

    Time frame: <2 weeks, up to 2 years of age

    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.

  8. Changes in adiposity in the child between iDTG and cDTG mothers

    Time frame: <2 weeks, up to 2 years of age

    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.

Secondary outcomes

  1. Changes in subcutaneous adipose tissue (SAT) function

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

    The SAT sample will reveal information regarding adipocyte hypertrophy, hypoxia, increased fibrosis and inflammation, decreased SAT mitochondrial respiration, and any altered metabolome/lipidome.

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Collaborators

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

Registry information

Acronym: ORCHID

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Aug 5, 2021
Registry last updated
Feb 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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