Study offers reassurance that dolutegravir-based ART during pregnancy is safe, effective
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Results of a multisite cohort study showed that dolutegravir-based antiretroviral therapy regimens are safe among pregnant women with HIV, and they more frequently led to viral suppression than other regimens commonly used in the U.S.
WHO recommends dolutegravir as first-line HIV therapy for everyone — including pregnant women. In U.S. guidelines, several regimens are categorized as “preferred” alongside dolutegravir, researchers noted.
“This is the first study to directly and systematically compare antiretroviral regimens that are listed as preferred in U.S. perinatal guidelines, such as atazanavir/ritonavir, darunavir, and raltegravir-based regimens, to dolutegravir in pregnancy,” Kunjal Patel, DSc, MPH, a senior research scientist at the Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, told Healio. “Our results confirm the recommendation of dolutegravir as preferred in U.S. perinatal guidelines, and provide evidence suggesting atazanavir-ritonavir and raltegravir provide lower HIV viral suppression at delivery compared to dolutegravir.”
Patel and colleagues evaluated pregnant women with HIV-1 infection enrolled in the Pediatric HIV/AIDS Cohort Study Surveillance and Monitoring for ART Toxicities (SMARTT) program, whose initial antiretroviral therapy (ART) in pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat, in combination with abacavir-lamivudine, tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC), TDF–lamivudine, or tenofovir alafenamide fumarate-FTC.
Among the pregnancies included in the study, 120 were among women who received dolutegravir as part of their initial ART in pregnancy; 464 were among women who received atazanavir-ritonavir; 185 were among women who received darunavir-ritonavir; 243 were among women who received oral rilpivirine; 86 were among women who received raltegravir; and 159 were among women who received elvitegravir-cobicistat.
According to the researchers, 96.7% of participants who received dolutegravir were virally suppressed at delivery, compared with 84% for atazanavir-ritonavir, 90.1% for darunavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat.
“The most important finding from our study is that there was a high probability of viral suppression at delivery with dolutegravir-based regimens,” Patel said. “We did not observe any clear differences in risks of adverse birth outcomes (preterm birth, low birth weight, small for gestational age, neonatal death) between dolutegravir and the other contemporary regimens commonly used in the United States that we evaluated.”
The researchers also conducted supplementary analyses that included participants from the Swiss Mother and Child HIV Cohort Study (MoCHiV) to improve the precision of the results.
“Our results support the use of dolutegravir-based regimens in pregnancy in the United States,” Patel said.
More clinical trials are needed to systemically evaluate the effectiveness and safety of new antiretroviral drugs in pregnancy, according to Patel.
“Clinical trials often do not include pregnant people, however, and generally would be limited to evaluating initiation of new regimens in pregnancy,” Patel said. “So, observational perinatal studies will continue to be important to evaluate new antiretroviral drugs in pregnancy after they are introduced into clinical practice among adults living with HIV.”
Perspective
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Dolutegravir-based ART is now the mainstay of first-line therapy for HIV infection worldwide. Dolutegravir is an integrase strand transferase inhibitor (INSTI) with a high genetic barrier to resistance, high potency and a favorable safety profile, so it was put on the WHO treatment guidelines as first-line therapy in 2018. However, at that time, there was a signal in an observational study called Tsepamo in Botswana of increased neural tube defects in children born of mothers on dolutegravir compared with the previously used first-line therapy, specifically efavirenz. However, that signal disappeared with further analysis in a larger cohort a year later, so dolutegravir was advanced to first line for all women and men worldwide in 2019. This study in The New England Journal of Medicine examined a cohort of pregnant mothers living with HIV using different ART regimens, along with their babies who were enrolled in the SMARTT study in the U.S. and the MoCHiV study in Switzerland, to compare outcomes of virologic suppression in the mothers and safety outcomes in the infants. Dolutegravir-based ART was superior to atazanavir-ritonavir, raltegravir and elvitegravir-cobicistat (which are a protease inhibitor, or PI, or other INSTI-based regimens) and was similar to a darunavir-ritonavir-based (a PI-based) regimen and an oral rilpivirine-based (a nonnucleoside reverse transcriptase inhibitor, or NNRTI-based) regimen in achieving the goal of therapy, which is viral suppression at delivery. Virologic suppression was 96.7% in the group of mothers who received dolutegravir. No clear differences were observed in the risk for adverse birth outcomes between dolutegravir and any of these other ART regimens.
Overall, this study provides reassurance that dolutegravir, which was chosen worldwide for its high potency in inhibiting HIV viral replication, is superior or comparable to other ART regimens in achieving the goal of virologic suppression among pregnant mothers with HIV, which is the most important predictor of preventing perinatal transmission to the infant. The study provides further evidence of the safety of dolutegravir when used by the mother to the infant, adding to recent data from other cohorts. Since dolutegravir is now first-line therapy worldwide, these findings are reassuring to millions of women living with HIV and their providers.
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