Dolutegravir-based antiretroviral therapies for HIV-1 effective in pregnancy

The study, which will be published online in NEJM on September 1, 2022, showed that pregnant people who took dolutegravir-based regimens had a high probability of being virally suppressed at delivery. There were no observed differences in the risks of adverse birth outcomes (preterm birth, low birth weight, small for gestational age, or neonatal death) between dolutegravir-based regimens and the other contemporary regimens.

"Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as 'Preferred' in U.S. perinatal guidelines" said Kunjal Patel, senior research scientist in the Department of Epidemiology at Harvard Chan School and lead author of the study.

Dolutegravir, a more recently approved antiretroviral drug, is part of a once-a-day regimen that has been shown to be more effective, easier to tolerate, and less likely to create new drug resistance in people with HIV-1 compared with other antiretroviral drugs. However, limited data have been available about its effectiveness and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the U.S. and Europe.

In the current observational study, the researchers compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as "Preferred" for use in pregnancy in the U.S. About half of the participants started ART before conception. At delivery, 96.7% of pregnancies of participants who received dolutegravir were virally suppressed, whereas those of participants who took atazanavir/ritonavir or raltegravir had viral suppression of 84.0% and 89.2%, respectively.

"We think the observed differences are due to dolutegravir's ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that's available as a fixed-dose combination," said Patel. "Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time."

Other Harvard Chan co-authors include Yanling Huo, Paige Williams, Deborah Kacanek, Denise Jacobson, Sean Brummel, and George Seage. The authors dedicate this work to the memory of their colleague and friend, Seage, who passed away in 2020.

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Deafness and Other Communication Disorders, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute (grants U01HD052102, U01HD052104, and P01HD103133), and the Swiss National Science Foundation (grant 201369).

"Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States," Kunjal Patel, Yanling Huo, Jennifer Jao, Kathleen M. Powis, Paige L. Williams, Deborah Kacanek, Lynn M. Yee, Ellen G. Chadwick, Stephanie Shiau, Denise L. Jacobson, Sean S. Brummel, Leila Sultan-Beyer, Christian R. Kahlert, Rebecca Zash, and George R. Seage III, for the Pediatric HIV/AIDS Cohort Study and the Swiss Mother and Child HIV Cohort Study, NEJM, online September 1, 2022.