The HIV drug regimen dolutegravir and emtricitabine/tenofovir alafenamide fumarate (DTG+FTC/TAF) is likely the safest and most effective drug for pregnant women living with HIV, according to new data presented at the 2020 Conference on Retroviruses and Opportunistic Infections (CROI) by Lameck Chinula, M.D., assistant professor with University of North Carolina at Chapel Hill (UNC).
Results of the phase 3 IMPAACT 2010 trial came as a welcome relief to HIV researchers after the 2018 Tsepamo study reported a risk of neural tube defects in infants born to mothers taking DTG-based regimens. In 2019, after additional data was collected on its safety among pregnant women, the World Health Organization (WHO) issued guidance that DTG is recommended as a first- and second-line antiretroviral treatment across all populations, including pregnant women.
Now, the new IMPAACT 2010 trial results “affirm the WHO recommendation to use DTG in all populations, including during pregnancy,” said Chinula, who is also clinical research site leader at UNC Project Malawi.
The National Institutes of Health–funded IMPAACT 2010 trial, also known as the VESTED study, began in January 2018 and included 643 women with HIV from Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the United States, and Zimbabwe.
Participants had never previously been on ART and began treatment during their second trimester. They were randomly assigned to one of three treatment arms: the legacy treatment efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF, Atripla) or dolutegravir plus the relatively new treatment emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) or the reformulated version, emtricitabine/tenofovir alafenamide fumarate (DTG+FTC/TAF).
Patients in the first treatment arm took the single tablet pill EFV/FTC/TDF, while those in the second and third arms took two pills: a DTG tablet taken with FTC co-formulated with either TDF or its new and improved formula, TAF.
About 98% of women in either DTG arm were virally suppressed by the time they delivered, compared to only 91% of the women in the EFV arm. Meanwhile, the DTG+FTC/TAF arm had the best outcomes in terms of safety and adverse events, with about a quarter of women reporting adverse outcomes compared to about a third of women in both the DTG+FTC/TDF and EFV/FTC/TDF arms.
These outcomes included pregnancy complications, preterm birth, low birth weight, and stillbirth. Although the rate of adverse events was high in the study, researchers pointed out that this is unlikely to be due to the study drugs, and is sadly on-par with the rate of adverse pregnancy outcomes in the broader population in many of the low- to middle-income countries in which the trial was based.
While all three regimens were safe and effective, Chinula noted that the results point to DTG+FTC/TAF as the likely most effective and safest option for pregnant women. DTG/TAF had significantly fewer infants born preterm, Chinula noted during his presentation. However, he added that a post hoc analysis showed that more patients experienced stillbirth in the DTG arms than the EFV arm, but this did not meet statistical significance. Investigators will continue digging into the data to see if they can glean any additional insights about the risk of stillbirth associated with any of these HIV regimens.
For now, clinicians should feel reassured that DTG-containing regimens are not only safe and effective in pregnant women, but the DTC regiment containing TAF may be even safer than TDF during pregnancy.
“When a woman living with HIV is expecting, she can be confident that the same antiretroviral therapy she takes every day to protect her own health also helps protect her future child from acquiring HIV,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, according to a press 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,” Fauci continued.
“These findings include the first of many insights we hope to glean from the VESTED study,” said Chinula, according to the release.