IMPAACT 2010 trial confirms recommendations for dolutegravir use in pregnancy
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Dolutegravir and emtricitabine/tenofovir alafenamide fumarate (DTG+FTC/TAF) may be the safest and most effective HIV treatment regimen for pregnant women, according to findings from CROI 2020.
The findings demonstrate that, when DTG-containing ART was initiated between 14 and 28 weeks of gestation, the therapy provided superior virologic efficacy compared with efavirenz (EFV)/FTC/tenofovir disoproxil fumarate (TDF).
“At the time the study started in early 2018, treatment regimens containing EFV and TDF were used broadly throughout the world, including in pregnant patients,” Lameck Chinula, MD, assistant professor in the department of obstetrics and gynecology’s division of global women’s health at the University of North Carolina School of Medicine and a clinical research site leader at UNC Project Malawi, told Healio. “As anticipated, dolutegravir (DTG) — and, to a lesser extent, tenofovir alafenamide fumarate, or TAF — have since become key components of first-line recommended ART in many programs globally because of their preferred efficacy and tolerability profiles.”
However, the safety and efficacy of these agents in pregnant women had not been examined, Chinula said.
“It was therefore important to obtain pregnancy safety and efficacy data for newer drugs, as DTG and TAF are expected to be widely used by women during pregnancy.”
Chinula and colleagues designed the IMPAACT 2010, or VESTED, trial to compare the safety and virologic efficacy of DTG plus FTC/TAF vs. DTG plus FTC/TDF.
Starting in January 2018, 643 pregnant women with HIV from four continents were randomly assigned 1:1:1 to start open-label DTG+FTC/TAF, DTG+FTC/TFD or EFV/FTC/TDF at 14 to 28 weeks gestational age. Treatment with ART for up to 14 days before study entry was permitted. Chinula and colleagues compared the combined DTG arms with the EFV arm for noninferiority, with a -10% margin, and superiority, in regard to delivery HIV RNA (< 200 copies/mL). Safety outcomes, which were compared across all arms, included composite adverse pregnancy outcome (preterm delivery before 37 weeks, small for gestational age, stillbirth or spontaneous abortion), maternal adverse events higher than grade 3 through 14 days postpartum, infant adverse events higher than grade 3 through 28 days and neonatal death before 28 days.
The study showed that although both regimens were very effective, DTG-containing ART regimens were even more effective in suppressing HIV by delivery than the EFV regimen. According to Chinula, 98% of women who received either of the DTG-containing regimens had viral suppression at the time of delivery and 91% of women who received EFV/FTC/TDF were virally suppressed at delivery.
The number of patients in each treatment arm was similar: 217 were randomly assigned to DTG+FTC/TAF, 215 to DTG+FTC/TDF and 211 to EFV/FTC/TDF. Baseline median patient characteristics included gestational age (21.9 weeks), HIV RNA (903 copies/mL) and CD4 count (466 cells/uL). Most patients (83%) were treated with ART prior to study entry (median, 6 days). Median antepartum follow-up was 17.4 weeks. Delivery HIV RNA, which was available for 605 women (94.1%), was <200 copies/mL for almost all women (395/405; 97.5%) in the combined DTG arms vs. 182 of 200 (91%) in the EFV/FTC/TDF arm (95% CI, 2%-10.7%).
Pregnancy outcomes were available for almost all women (n = 640; 99.5%). Significantly fewer women (24.1%) who received DTG+FTC/TAF had an adverse pregnancy outcome, according to Chinula, compared with 32.9% of women who received DTG+FTC/TDF and 32.7% of women who received EFV/FTC/TDF.
“98% of women who received either of the DTG-containing regimens had viral suppression at the time of delivery,” Chinula told Healio. “In contrast, 91% of women who received EFV/FTC/TDF were virally suppressed at delivery.”
Although stillbirth was more common with DTG+FTC/TAF (3.7%) and DTG+FTC/TDF (5.2%) vs. EFV/FTC/TDF (1.9%), neonatal death was more common with EFV+FTC/TDF (4.8%) than DTG+FTC/TAF (1%; P = .019) or DTG+FTC/TDF (1.5%). Combined stillbirth or neonatal death rates were similar by arm in the post-hoc analysis.
At least one greater than grade 3 adverse event was recorded in 148 (23%) women and 105 (17%) infants. During the study, two infants, one in each of the DTG arms, were diagnosed with HIV within 14 days of birth and one infant was born to a mother who had poor viral suppression throughout pregnancy and the other was from a mother who was largely virally suppressed.
“When a woman living with HIV is expecting, she can be confident that the same ART she takes every day to protect her own health also helps protect her future child from acquiring HIV,” said NIAID Director Anthony S. Fauci, MD, said in a news release. “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.”
Chinula added that the study showed that DTG-containing treatment regimens had a superior virologic efficacy and safety profile compared with EFV/FTC/TDF.
“Overall, the study results reaffirm current international recommendations for use of DTG among all populations, including pregnant women,” she said. “Results also suggest that TAF may be preferable to TDF in pregnancy.” – by Caitlyn Stulpin
References:
Chinula L, et al. Abstract 130LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
NIH. Newer anti-HIV drugs safest, most effective during pregnancy. https://www.nih.gov/news-events/news-releases/newer-anti-hiv-drugs-safest-most-effective-during-pregnancy. Accessed on March 11, 2020.
Disclosures: Chinula and Fauci report no relevant financial disclosures.
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