1. Dolutegravir-based antiretroviral therapy regimens effectively suppressed maternal viral load during pregnancy, supporting their use to prevent vertical transmission.
2. Dolutegravir, emtricitabine, and tenofovir alafenamide fumarate carried relatively low risk of adverse fetal outcomes.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Initiation of antiretroviral therapy (ART) for pregnant women infected with HIV-1 is important for maternal-fetal health; however, there is limited information on ART safety and efficacy in pregnancy. This multicenter, open-label, randomized, controlled, phase 3 clinical trial compares the safety and efficacy of three ART regimens for use in pregnancy. Pregnant women infected with HIV-1 at 14-28 weeks’ gestation and had no previous ART use or pregnancy complications were eligible for this trial. Participants were randomized equally to three ART regimens and stratified by gestational age. The primary outcome was proportion of participants with HIV-1 viral suppression of <200 copies of RNA per mL within 14 days of delivery. Absolute efficacy of each regimen in suppressing viral load and adverse pregnancy outcomes were compared as well. According to study results, regimens containing dolutegravir were most effective at suppressing viral load in pregnant women. Additionally, the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest rates of adverse pregnancy outcomes. These results together support the use of dolutegravir along with adjuvant agents emtricitabine and tenofovir alafenamide fumarate to suppress viral load in HIV-1 positive pregnant women.
Click to read the study in The Lancet
Relevant Reading: Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception
In-Depth [randomized controlled trial]: This study included 22 international centers and 643 eligible participants to assess the relative efficacy of three ART regimens: dolutegravir with emtricitabine and tenofovir alafenamide fumarate (TAF); dolutegravir with emtricitabine and tenofovir disoproxil fumarate (TDF); and efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Demographic characteristics were comparable among the three groups. When the results from dolutegravir-containing groups were pooled and compared to the efavirenz-based group, statistically significant differences in the rates of adequate HIV-1 RNA suppression were observed, with estimated 98% suppression in pooled dolutegravir groups compared to 91% suppression in efavirenz group (estimated difference of 6.5% [95% CI 2.0-10.7]; p=0.0052). Adequate viral suppression was defined as HIV-1 RNA <200 copies/mL. This difference persisted even after stratifying participants by viral load at time of enrollment (>200 copies/mL vs. <200 copies/mL). In terms of safety, TAF was associated with lower risk of adverse pregnancy outcomes compared to TDF upon evaluation of a range of adverse events including fetal infection, infant mortality within the first month of life, and congenital abnormalities.
This study excluded multiple gestation pregnancies or pregnancies complicated with fetal abnormalities. Additionally, participants with psychiatric complaints or gestational ages outside of the 14-28 week window at time of enrollment were excluded, which amounts to a significant proportion of pregnant women. Despite these limitations, this study contributes to the limited body of data supporting the use of dolutegravir-based ART regimens during pregnancy.
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