“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in theDr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.