Study: Dolutegravir-based Antiretroviral Therapies for HIV-1 Effective in Pregnancy

A new study found that dolutegravir (Tivicay)-based antiretroviral therapies (ART) for HIV-1 are more effective for pregnant people than some other ART regimens that are commonly used in the United States and Europe.

Dolutegravir is a second-generation integrase strand transfer inhibitor approved for the treatment of HIV-1 in combination with other antiretrovirals for both treatment-experienced and treatment-naïve patients. The drug works to impede HIV DNA integration by binding to magnesium at the integrase active site, thereby blocking the strand transfer step and completion of the HIV replication cycle.

Dolutegravir is a more recently approved ART that is a part of a once-a-day regimen found 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.

In June 2020, the FDA approved dolutegravir tablets (Tivicay and Tivicay PD, ViiV Healthcare) for suspension to treat HIV-1 infection in pediatric patients at least 4 weeks of age and weighing at least 6.61 pounds in combination with other antiretroviral treatments. Dolutegravir tablets are intended to treat pediatric patients at least 4 weeks old and at least 6 pounds who have never been treated for HIV or who have been treated, but not with an integrase strand transferase inhibitor class drug.

Even with this information, there are limited data available about its efficacy and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the United States and Europe.

Researchers from the Harvard T.H. Chan School of Public Health conducted the study, which demonstrated 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 (such as 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 US perinatal guidelines” said lead study author Kunjal Patel, senior research scientist in the Department of Epidemiology at Harvard Chan School, in a press release.

The current study compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as “preferred” use in pregnancy in the United States. Approximately half of the participants started ART before conception, and at delivery, 96.7% of pregnancies among participants administered dolutegravir were virally suppressed. However, the participants who received atazanavir/ritonavir or raltegravir had viral suppression of 84% 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,” Patel said in the press release. “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.”

REFERENCE

Dolutegravir-based antiretroviral therapies for HIV-1 effective in pregnancy. Harvard T.H. Chan School of Public Health. September 1, 2022. Accessed September 7, 2022. https://www.hsph.harvard.edu/news/press-releases/dolutegravir-antiretroviral-hiv-pregnancy/