Dolutegravir-Based ART in Pregnancy

For pregnant persons with human immunodeficiency virus (HIV) infection, a dolutegravir-based regimen is preferred as first-line antiretroviral therapy (ART). Among nonpregnant adults, dolutegravir-based ART is more effective, is less likely to be discontinued because of side effects, has a higher barrier to resistance, and has fewer drug interactions than other types of ART.

The efficacy, effectiveness, and safety of dolutegravir in pregnancy have been compared with those of efavirenz including comparisons in three randomized trials. The DolPHIN-1 and DolPHIN-2 trials and the IMPAACT 2010/VESTED trial reported better viral suppression at delivery and either no evidence of a difference or a lower frequency of adverse birth outcomes with dolutegravir that was initiated in early or late pregnancy than with efavirenz.

Study by Kunjal Patel and Team

Kunjal Patel and team conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included:

• Dolutegravir
• Atazanavir–ritonavir
• Darunavir–ritonavir
• Oral rilpivirine
• Raltegravir
• Elvitegravir–cobicistat

Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non–dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results.

Study Results

Of the pregnancies in the study:

• 120 were in participants who received dolutegravir
• 464 in those who received atazanavir–ritonavir
• 185 in those who received darunavir–ritonavir
• 243 in those who received rilpivirine
• 86 in those who received raltegravir
• 159 in those who received elvitegravir–cobicistat

The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception.

Viral Suppression and Birth Outcomes

Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were:

• 84.0% for atazanavir–ritonavir
• 89.2% for raltegravir
• 89.8% for elvitegravir–cobicistat

(Adjusted risk differences vs. dolutegravir, −13.0 percentage points, −17.0 percentage points, and −7.0 percentage points.)

The observed risks of preterm birth were 13.6 to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between non–dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar.

Atazanavir–ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non–dolutegravir-based ART, although samples were small.

Source: Kunjal Patel, D.Sc., Yanling Huo, M.S., Jennifer Jao; N Engl J Med 2022;387:799-809. DOI: 10.1056/NEJMoa2200600