Dolutegravir shows promise in pregnancy

Comparing the use of common antiretroviral therapy (ART) regimens in pregnancy suggests that dolutegravir-based regimens have a higher probability of human immunodeficiency virus type 1 (HIV-1) viral suppression at delivery.

In a study published in the New England Journal of Medicine, researchers compared the effectiveness and safety of dolutegravir-based ART to five ART regimens recommended for use in pregnancy in the US and Europe: atazanavir–ritonavir, darunavir–ritonavir, oral rilpivirine, raltegravir, and elvitegravir–cobicistat.  The investigators compared viral suppression at delivery and the risks of infants being born preterm, with low birth weight, and being small for gestational age.

“Our study showed that dolutegravir-based regimens had a high probability of maternal viral suppression at delivery, and there were no observable differences in the risks of adverse birth outcomes, such as preterm birth, low birth weight, small for gestational age, or neonatal death, between dolutegravir and the other contemporary regimens,” explained co-author Dr Ellen Chadwick, Director of Section of Pediatric, Adolescent and Maternal HIV Infection at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine, both US. “This is great news, since dolutegravir also has other important benefits compared to older antiretroviral drugs,” including that it is taken once-a-day, is more tolerable and is less likely to result in resistance mutations compared with other antiretroviral drugs.

“This is one of the largest studies to examine the effectiveness and safety of dolutegravir in pregnancy compared to regimens that have been commonly used during pregnancy in the US and Europe,” added co-author Dr Jennifer Jao, an infectious diseases physician at Lurie Children’s and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “Our results show viral suppression at delivery in considerably more participants.”

The observational study included more than 1,250 pregnancies, 120 in participants receiving dolutegravir, 464 receiving atazanavir–ritonavir, 185 receiving darunavir–ritonavir, 243 receiving rilpivirine, 86 receiving raltegravir and 159 receiving elvitegravir–cobicistat. Approximately half of the participants started ART before conception.

Viral suppression was present at delivery in 96.7 percent of the pregnancies in participants who received dolutegravir, compared to 84 percent in atazanavir–ritonavir recipients, 89.2 percent for raltegravir, and 89.8 percent for elvitegravir–cobicistat. Moreover, the observed risk of preterm birth was 13.6 to 17.6 percent in these participants – after risk adjustment the authors concluded that the risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between dolutegravir and non–dolutegravir-based ART.

The researchers concluded that atazanavir–ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir, and there were no clear differences in risks to infants but cautioned that the samples were small.

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health and others.