During a multicenter, open-label, randomized, controlled, phase 3 trial of antiretroviral therapy regimens among pregnant women, dolutegravir, emtricitabine, and tenofovir alafenamide fumarate triple therapy was found to have the lowest composite frequency of adverse outcomes, according to the results of a study published in The Lancet.
IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) and VESTED (Virologic Efficacy and Safety of ART Combinations with TAF/TDF, EFV, and DTG; ClinicalTrials.gov Identifier: NCT03048422) recruited pregnant women with HIV-1 at 22 research centers located in 9 countries in North America, South America, Asia, and Africa from 2018 to 2019. At 14 to 28 weeks’ gestation, participants were stratified by gestational age and country and were randomly assigned to receive dolutegravir, emtricitabine, and tenofovir alafenamide fumarate (n=217); dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (n=215); or efavirenz, emtricitabine, and tenofovir disoproxil fumarate (n=211). Pregnancy outcomes and viral suppression status were assessed through 50 weeks’ postpartum.
The median age of participants was 26.6 years (interquartile range [IQR], 22.5-31.6); most lived in Zimbabwe (39%), were Black (91%), were at 19 to 23 gestational weeks at enrollment (39%), had median HIV-1 RNA of 902.5 copies/mL (IQR, 152.0-5182.5), and had a CD4 count of 466 copies/mL (IQR, 308-624). At delivery, recipients of dolutegravir-based therapies had higher viral suppression at <200 copies/mL (98% vs 91%; P =.0052) and <50 copies/mL (95% vs 80%; P <.0001).
A total of 30% of the study participants experienced an adverse pregnancy outcome. Therapy with alafenamide was associated with a reduced composite outcome of small for gestational age, preterm delivery, or stillbirth compared with disoproxil (group difference, -8.8%; 95% CI, -17.3% to -0.3%; P =.043) or efavirenz (group difference -8.6%; 95% CI, -17.1% to -0.1%; P =.047). Alafenamide was associated with a numerically smaller number for all 3 adverse events compared with the other treatments except for stillbirths (alafenamide 3.7% vs efavirenz 1.9%).
Grade 3 adverse events were reported by 21% of the alafenamide, 26% of the disoproxil, and 22% of the efavirenz groups. One study participant died from sepsis 2 weeks after cesarean delivery (alafenamide recipient).
Median birthweights among the alafenamide, disoproxil, and efavirenz cohorts were 3160 g (IQR, 2850-3500), 3065 g (IQR, 2800-3440), and 3000 g (IQR, 2705-3325); 6%, 10%, and 12% of infants had low birthweight (<2500 g); 1%, 2%, and 5% died by age 28 days; and mean creatinine clearance at birth was 52.5±30.9, 53.3±68.8, and 49.6±26.1 mL/min, respectively.
Because this study was limited by the choice to recruit women 14 weeks into their pregnancy, it remains unclear whether any of the studied drug regimens could have had adverse effects during early pregnancy.
The study authors concluded that triple therapy of dolutegravir, emtricitabine, and tenofovir alafenamide fumarate was associated with the fewest adverse pregnancy outcomes and had high viral suppression among pregnant women with HIV-1.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Lockman S, Brummel SS, Ziemba L, et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2021;397(10281):1276-1292. doi:10.1016/S0140-6736(21)00314-7