P2010: Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and their Infants “VESTED”

Full Title: P2010: Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and their Infants “VESTED”: Virologic Efficacy and Safety of ART Combinations with TAF/TDF, EFV, and DTG

This is a clinical trial conducted under the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and funded by the U.S. National Institutes of Health.

Purpose: To compare the virologic efficacy and safety of three antiretroviral regimens for HIV-1-infected pregnant women and to compare the safety of these regimens for their infants.

Primary Objectives
To determine the following among HIV-1-infected pregnant women and their infants:

• Whether treatment initiated during pregnancy with a DTG-containing regimen is superior to EFV/FTC/TDF with regard to virologic efficacy (HIV-1 RNA <200 copies/mL) at delivery
• Whether rates of the following safety outcomes differ for any pairwise regimen comparison 
  • Adverse pregnancy outcomes (spontaneous abortion, fetal death, preterm delivery, or small for gestational age)
  • Maternal grade 3 or higher adverse events through 50 weeks postpartum
  • Infant grade 3 or higher adverse events through 50 weeks postpartum

Secondary Objectives
To evaluate the following among HIV-1-infected pregnant women and their infants:

• Whether treatment initiated during pregnancy with a DTG-containing regimen is non-inferior to EFV/FTC/TDF with regard to virologic efficacy (HIV-1 RNA <200 copies/mL) at delivery
• Whether the following differ when comparing a DTG-containing regimen initiated during pregnancy to EFV/FTC/TDF:
  • Proportion of mothers with HIV-1 RNA <50 copies/mL at delivery
  • Proportion of mothers with HIV-1 RNA <200 copies/mL at 50 weeks postpartum
• Whether the following differs for any pairwise regimen comparison:
  • Proportion of mothers with HIV-1 RNA <200 copies/mL at delivery and at 50 weeks postpartum using the standardized FDA snapshot algorithm
• Whether rates of the following differ for any pairwise regimen comparison:
  • A composite outcome of spontaneous abortion, fetal death, preterm delivery, small for
  • gestational age, or major congenital anomaly
  • A ranked composite infant safety outcome measure through 50 weeks postpartum
  • Infant HIV infection through 50 weeks postpartum
  • Infant mortality through 50 weeks postpartum
  • Infant bone toxicity at 26 weeks postpartum
  • Maternal bone toxicity at 50 weeks postpartum
  • Markers of maternal and infant renal toxicity through 50 weeks postpartum
  • Antiretroviral drug resistance observed with each maternal ART regimen:
    •  Among mothers who experience virologic failure (at baseline and time of virologic failure)
    •  Among HIV-infected infants (at time of HIV diagnosis)
• Whether treatment initiated during pregnancy with each regimen is non-inferior with regard to preterm delivery and, separately, small for gestational age, for any pairwise regimen comparison.