Clinical trial NCT04991402: Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir
Official title: Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: HIV
Obesity
Obesity, Infant
Maternal Obesity During Childbirth
Maternal Obesity Complicating Pregnancy
Keywords: HIV
Dolutegravir
Metabolic health
Maternal obesity
Pregnancy
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Northwestern University
name: University of Cape Town
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Hawaii
name: Tufts University
name: Albert Einstein College of Medicine
First posted: 2021-08-05
Enrollment: 1920
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Difference in excess gestational weight gain between pregnant women living with HIV and HIV negative pregnant women
timeFrame: <18 weeks (baseline), 32-34 weeks
measure: Difference in gestational weight gain between iDTG and cDTG pregnant women
timeFrame: <18 weeks (baseline), 32-34 weeks
measure: Change in adipose tissue mass compared between pregnant women living with HIV and HIV negative pregnant women
timeFrame: <18 weeks (baseline), 32-34 weeks
measure: Change in adipose tissue mass compared between iDTG and cDTG mothers
timeFrame: <18 weeks (baseline), 32-34 weeks
measure: Differences in maternal metabolic health post-partum between mothers living with HIV and HIV negative mothers
timeFrame: <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum
measure: Differences in maternal metabolic health post-partum between iDTG and cDTG mothers
timeFrame: <18 weeks antenatal, 24 weeks postpartum, and 24 months postpartum
measure: Changes in adiposity in the child between HIV positive mothers and HIV negative mothers
timeFrame: <2 weeks, up to 2 years of age
measure: Changes in adiposity in the child between iDTG and cDTG mothers
timeFrame: <2 weeks, up to 2 years of age
Secondary outcomes:
measure: Changes in subcutaneous adipose tissue (SAT) function
timeFrame: <18 weeks (baseline), 32-34 weeks antenatal, 24 months postpartum
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Gugulethu Community Health Center
city: Cape Town
country: South Africa
facility: Mitchell's Plain Community Health Center
Study officials:
affiliation: ICAP at Columbia University
name: Elaine J. Abrams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Jennifer Jao, MD
role: PRINCIPAL_INVESTIGATOR
References: