Although DTG currently is not a desirable medication for women to take pre-conception (see Dolutegravir in Early Pregnancy: Updates on Possible Risk of Neural Tube Defects), findings from the DolPHIN study suggest that it may be a very useful agent for women who start ART during late pregnancy. The DolPHIN study team randomized 60 pregnant women who were initiating ART in their 3rd trimester to one of two regimens: DTG plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) or efavirenz (EFV) plus 2 NRTIs. At 2 weeks postpartum, all women were given EFV plus 2 NRTIs. The study's primary endpoint was maternal DTG concentrations; secondary endpoints included HIV-1 viral load postpartum, safety, tolerability; and infant cord blood pharmacokinetic parameters. The two groups were well matched at baseline. Interestingly, postpartum DTG area under the curve (AUC), Cmax, and Ctrough (37,575 ng/mL, 2,843 ng/mL, and 696 ng/mL, respectively) did not differ much from 3rd-trimester values (35,322 ng/mL, 2,534 ng/mL, 642 ng/mL, respectively); these differences were not statistically significant. During the 3rd trimester, approximately one third of the women on DTG exhibited troughs below the researchers' suggested minimum effective concentration.
Despite this, women assigned to the DTG arm achieved an undetectable viral load approximately twice as fast as women in the EFV arm, and a higher proportion of them (compared with women receiving EFV) had suppressed viral loads by the 2 week postpartum visit (69% vs 38.7%; p = .02). No birth defects were seen in infants in the DTG arm, while 3 cases of birth defects (skeletal, limb, or cardiac malformations, or neonatal sepsis) were observed in infants in the EFV arm. One stillbirth occurred with a mother in the DTG arm. The study follow-up was brief, therefore there were no available data on perinatal HIV transmissions.
Clinical Bottom Line
The general standard of care for women is to initiate ART as early as possible and prior to pregnancy. However, if ART is initiated later during pregnancy, data from DolPHIN support using a DTG-containing regimen to help women achieve more rapid and complete viral suppression.
Orrell C, Kintu K, Coombs JA, et al. DolPHIN-1: Randomized controlled trial of dolutegravir (DTG)- versus efavirenz (EFV)-based therapy in mothers initiating antiretroviral treatment in late pregnancy. In: Program and abstracts of the 22nd International AIDS Conference; July 23-27, 2018; Amsterdam. Abstract THAB0307LB.