Dolutegravir-based antiretroviral treatment was associated with a higher rate of undetectable viral load at delivery in pregnant women, results of the IMPAACT 2010 trial show. A regimen containing both dolutegravir and tenofovir alafenamide was associated with fewer pre-term births and neonatal deaths than efavirenz-based treatment.
The findings were presented to the Conference on Retroviruses and Opportunistic Infections by Professor Lameck Chinula of University of North Carolina Project – Malawi. All conference presentations are taking place online this year to minimise the risk of coronavirus transmission.
Dolutegravir-based treatment is being introduced as the preferred first-line regimen in many countries following World Health Organisation recommendations. Dolutegravir is preferred as the cornerstone of first-line treatment because of high efficacy, a high barrier to resistance and few side effects. But the efficacy and safety of dolutegravir-based treatment in pregnancy is unclear.
IMPAACT 2010, also known as VESTED (Virologic Efficacy and Safety of Antiretroviral Therapy Combinations with TAF/TDF, EFV and DTG) was designed to compare the safety and efficacy of two dolutegravir-containing regimens with the standard of care in pregnant and breastfeeding women. Chinula noted that the viral suppression outcomes in IMPAACT 2010 are among the best seen in trials in pregnant women.
Pre-term delivery and other adverse birth outcome occurred more often in the efavirenz arm.
The study investigators concluded that the findings support the use of dolutegravir-based treatment in pregnant women, in line with World Health Organisation guidelines, and suggest that use of TAF may be preferable to TDF in pregnancy.
“Findings from the VESTED study suggest that a drug regimen containing dolutegravir provides the safest, most effective HIV treatment available during this critical time for women and their infants,” said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, sponsor of the trial.
Abstract
We compared the safety and virologic efficacy of dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) vs. DTG + FTC/tenofovir disoproxil fumarate (TDF) vs. efavirenz (EFV)/FTC/TDF in pregnant women.
Pregnant women with HIV-1 in 9 countries were randomized 1:1:1 to start open-label DTG+FTC/TAF, DTG+FTC/TDF, or EFV/FTC/TDF at 14-28 weeks gestational age (GA). Up to 14 days’ pre-entry antiretroviral treatment (ART) was permitted. In primary efficacy analysis, we compared the combined DTG-containing arms to the EFV arm for non-inferiority (-10% margin), then superiority, with regard to delivery HIV RNA<200 cp/mL. Safety outcomes compared between all arms were a) composite adverse pregnancy outcome (preterm delivery [PTD]<37 weeks, small for GA [SGA]<10th centile, stillbirth [SB] or spontaneous abortion [SAB]); b) maternal grade>3 adverse event (AE) through 14 days postpartum; and c) infant grade>3 AE through 28 days. Neonatal death (NND, <28 days) was also evaluated.
We randomized 643 women: 217 to DTG+FTC/TAF, 215 to DTG+FTC/TDF, and 211 to EFV/FTC/TDF. Baseline medians were: GA 21.9 weeks, HIV RNA 903 cp/mL, CD4 count 466 cells/uL; 83% took ART prior to entry (median 6 days). Median antepartum follow-up was 17.4 weeks. Delivery HIV RNA, available for 605 (94.1%) women, was 3 AE occurred in 148 (23.0%) women and 105 (17.0%) infants (all by-arm p-values 0.05). Two babies were diagnosed with HIV at
DTG-containing ART started at GA 14-28 weeks had superior virologic efficacy at delivery to EFV/FTC/TDF. DTG+FTC/TAF had the lowest composite frequency of adverse pregnancy outcomes. Maternal and infant AE outcomes were similar by arm.
Authors
Lameck Chinula, Sean S Brummel, Lauren Ziemba, Lynda Stranix-Chibanda, Anne Coletti, Chelsea Krotje, Patrick Jean-Philippe, Lee Fairlie, Tichaona Vhembo
[link url="http://www.aidsmap.com/news/mar-2020/dolutegravir-based-hiv-treatment-safest-and-most-effective-choice-pregnant-women"]Full Aidsmap report[/link]
[link url="http://www.croiconference.org/sessions/safety-and-efficacy-dtg-vs-efv-and-tdf-vs-taf-pregnancy-impaact-2010-trial"]CROI 2020 abstract[/link]