In a multicenter, open-label, randomized, controlled phase 3 study of antiretroviral regimens in pregnant women, triple therapy with dolutegravir, emtricitabine and tenofovir alafenamide fumarate was found to have the lowest combined incidence of side effects, 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 in 22 research centers in 9 countries in North America, South America, Asia, and Africa from 2018 to 2019. In weeks 14 to 28 of pregnancy, participants were stratified by gestational age and country and randomized to 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 results and virus suppression status were assessed up to 50 weeks after birth.
The average age of the participants was 26.6 years (interquartile range [IQR], 22.5-31.6); most of them lived in Zimbabwe (39%), were black (91%), were between 19 and 23 weeks of gestation (39%) at study inclusion, had a 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 virus suppression at <200 copies / ml (98% vs. 91%; P = 0.0052) and <50 copies / ml (95% vs. 80%; P < 0.0001).
A total of 30% of the study participants had an undesirable outcome of the pregnancy. Alafenamide therapy was associated with a reduced combined outcome of small for gestational age, premature birth, or stillbirth compared to disoproxil (group difference, -8.8%; 95% CI, -17.3% to -0.3%; p = 0.043) or efavirenz (group difference -8.6%; 95% CI, -17.1% to -0.1%; P = 0.047). Alafenamide was found to be less numerous in all 3 adverse events compared to the other treatments with the exception of stillbirths (alafenamide 3.7% vs.
Grade 3 adverse reactions were reported by 21% of the alafenamide, 26% of the disoproxil, and 22% of the efavirenz groups. One study participant died of sepsis 2 weeks after delivery by caesarean section (alafenamide recipients).
The median birth weights of 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 the infants had a low birth weight (<2500 g); 1%, 2% and 5% died at 28 days of age; and the mean creatinine clearance at birth were 52.5 ± 30.9, 53.3 ± 68.8 and 49.6 ± 26.1 ml / min, respectively.
Since this study was constrained by the choice of women in the 14th week of pregnancy, it remains unclear whether any of the drug regimens examined could have had side effects during early pregnancy.
The study authors concluded that triple therapy with dolutegravir, emtricitabine, and tenofovir alafenamide fumarate was associated with the fewest adverse pregnancy outcomes and was associated with high levels of viral suppression in pregnant women with HIV-1.
Disclosure: Several study authors stated links with the pharmaceutical industry. For a full list of the author’s disclosures, see the original reference.
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 Antiretroviral HIV regimens initiated during pregnancy (IMPAACT 2010, randomized, controlled, open-label study): Lancet. 2021; 397 (10281): 1276-1292. doi: 10.1016 / S0140-6736 (21) 00314-7
This article originally appeared on Infectious Disease Advisor