10 March 2021
The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network is delighted to announce the presentation of important findings from IMPAACT 2010 (the VESTED study) at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI) today.
The Network congratulates the protocol team and study sites for completion of this study and presentation of findings of great importance to the health of women living with HIV and their babies.
IMPAACT 2010/VESTED was a Phase III, three-arm, randomized, open-label study of pregnant women with HIV initiating either a dolutegravir (DTG)-containing antiretroviral regimen or an efavirenz (EFV)-containing antiretroviral regimen at 14-28 weeks gestation. When the study began, treatment regimens containing EFV and TDF were commonly recommended and used worldwide. Newer regimens containing DTG were also being added to treatment recommendations but had not been evaluated among pregnant and postpartum women. The study was designed to evaluate whether DTG-containing regimens would be non-inferior to EFV/FTC/TDF with regard to virologic efficacy at delivery and whether rates of adverse pregnancy outcomes, maternal adverse events, and infant adverse events would differ between the regimens.
Findings presented at CROI were based on data collected during pregnancy and through the first year postpartum. Results are described below.
Primary Study Results
A total of 643 pregnant women and their unborn babies were enrolled in IMPAACT 2010/VESTED between January 2018 and February 2019 at 22 IMPAACT sites in Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the United States, and Zimbabwe. Pregnant women were randomly assigned, in pairs with their babies, to one of three ARV regimen groups: EFV/FTC/TDF, DTG+FTC/TDF, or DTG+FTC/TAF.
Results, presented by Lameck Chinula on behalf of the IMPAACT 2010 Protocol Team, showed that the DTG-containing regimens and the EFV-containing regimen were highly effective for viral suppression. At the week 50 postpartum visit, 96% of women had a suppressed viral load (<200 copies/mL), regardless of which regimen they were assigned to. However, women receiving the EFV-containing regimen were more likely to experience virologic failure (HIV viral load ≥200 copies/mL) at some time during follow-up compared to women receiving the DTG-containing regimens (10% versus 4-5%). As such, regimen changes due to virologic failure were more common among women receiving the EFV-containing regimen.
All three regimens were found to be safe through 50 weeks postpartum. Rates of maternal and infant adverse events were similar for all three regimens. As reported previously, use of DTG+FTC/TAF led to the best pregnancy outcomes. Infant death as well as a composite of still birth and infant death were more common with use of the EFV-containing regimen. No neural tube defects were identified.
Four babies were identified with HIV infection. All of these babies were breastfed and received antiretroviral prophylaxis. Two had positive tests within 14 days postpartum. The other two tested positive at six weeks postpartum and at 50 weeks postpartum. Three of the four were born to mothers receiving a DTG-containing regimen. The fourth was born to a mother receiving the EFV-containing regimen. Two of the infections appear to have occurred despite the mother having a suppressed HIV viral load based on testing prior to identification of the baby’s infection.
Focus on Weight Gain
Recent studies have identified weight gain as a potential concern among non-pregnant adults receiving DTG and/or TAF. Treatment with EFV/FTC/TDF has been associated with low weight gain in pregnancy, and both low and high weight gain have been associated with adverse pregnancy outcomes.
Risa Hoffman reported on maternal weight changes during pregnancy. Women receiving DTG+FTC/TAF were more likely to have weight gain that approached the recommended standards established by the Institute of Medicine for the second and third trimesters of pregnancy, compared to women receiving DTG+FTC/TDF or EFV/FTC/TDF. Women receiving DTG+FTC/TAF were also more likely to experience higher than recommended weight gain during pregnancy, whereas women receiving EFV/FTC/TDF were more likely to experience lower than recommended weight gain during pregnancy. Women with low weight gain were more likely to have an adverse pregnancy outcome compared to women with normal weight gain; having an infant small for gestational age accounted for most of this difference.
Analyses of weight gain are complex in the context of pregnancy. Further analyses of IMPAACT 2010 data are planned to better understand the implications of antepartum and postpartum weight changes for maternal and infant health.
Other news and results from IMPAACT 2010/VESTED:
- NIH Press Release Related to CROI 2020 Abstract
- NIH Press Release Upon Study Initiation
- CROI 2020 Oral Presentation
- CROI 2020 Oral Presentation for the ICAB