First-Line HIV Treatment Proves Mettle in Pregnant Patients

The HIV agent dolutegravir (Tivicay) was tied to greater viral suppression for pregnant patients with HIV-1, according to a cohort study.

Among patients who used dolutegravir during pregnancy, viral suppression at delivery was achieved in nearly 96.7% of participants, reported Kunjal Patel, DSc, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues.

Two of those other therapies provided less viral suppression at delivery -- atazanavir plus ritonavir (84%) and raltegravir (Isentress; 89.2%). However, viral suppression with darunavir (Prezista) plus ritonavir (90.1%) could make it a feasible alternative to dolutegravir, they wrote in the New England Journal of Medicine.

Viral suppression at delivery was also present for 89.8% of those who received elvitegravir-cobicistat.

They also noted that there were no clear differences in adverse birth outcomes between patients who took dolutegravir-based antiretroviral therapy (ART) compared to those who received other therapies.

According to U.S. perinatal guidelines, raltegravir, atazanavir-ritonavir, darunavir-ritonavir, and dolutegravir are the "preferred" medications to treat HIV in pregnancy. Rilpivirine is considered as an "alternative" nonnucleoside reverse-transcriptase inhibitor, and elvitegravir-cobicistat is not recommended in pregnancy due to insufficient pharmacokinetic levels in the third trimester, Patel's group wrote.

"Our results support the use of dolutegravir in pregnancy," Patel told MedPage Today. She added that a dolutegravir-based regimen is preferred as first-line ART for HIV/AIDS in the U.S. in adults who are not pregnant. However, the current study included pregnancies that occurred both before and after a warning about potential increased risk of neural-tube defects associated with dolutegravir came out. This may have resulted in residual confounding for the comparison of non-dolutegravir-based ART with dolutegravir, the authors explained.

Lynne Mofenson, MD, of the Elizabeth Glaser Pediatric AIDS Foundation, confirmed that dolutegravir is already a preferred drug, from the class of medications called integrase strand transfer inhibitors (INSTIs), in pregnancy. Raltegravir has a much lower barrier to resistance and requires twice daily administration during pregnancy, she stated.

"The finding that [dolutegravir] has improved viral suppression at delivery confirms [dolutegravir] preference over raltegravir in pregnancy," Mofenson, who was not involved in the study, told MedPage Today via email.

Patel's group pointed out that in non-pregnant adults, dolutegravir has proven more effective, with fewer side effects and drug interactions, not to mention a higher barrier to resistance, than other medications on the market. But there are little data comparing the safety and efficacy of dolutegravir-based therapies to other ARTs, specifically during pregnancy, they stated.

Study participants came from the pediatric SMARTT study. They were enrolled between April 2007 and January 2020. Participants whose initial ART during pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat were included in the analysis.

The researchers compared the number of patients who experienced viral suppression at delivery on each medication (viral load <200 copies per milliliter), as well as the risks of adverse birth outcomes including preterm birth, low birthweight, or small for gestational age (SGA). They adjusted their analyses for covariates including age at conception, race and ethnic group, education, timing of maternal HIV infection diagnosis, preconception or post-conception initiation of ART, tobacco and alcohol use during pregnancy, and any sexually transmitted infection during pregnancy.

Of all participants included in the study, 120 received initial dolutegravir-based ART, while about 464 got atazanavir-ritonavir, 185 received darunavir-ritonavir, 243 were on rilpivirine, 86 got raltegravir, and 159 received elvitegravir-cobicistat. The median age of participants at conception was 29, and about half began ART before getting pregnant.

In an analysis that compared oral rilpivirine with dolutegravir, viral suppression was present at delivery for 96.8% of participants who received rilpivirine and 96.3% who received dolutegravir.

Overall, the risk of preterm birth for patients who received ART during pregnancy was between 13.6% and 17.6% across different therapies, the researchers found. But there were no significant differences between therapies in the risks of preterm birth, low birthweight, and SGA in adjusted analysis.

Patel's group found that among patients who took dolutegravir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat, starting ART prior to pregnancy was linked with a lower risk of any adverse birth outcome versus starting treatment during pregnancy.

Studly limitations included not enough information on risk factors for preterm birth and low birthweight, including parity, previous preterm birth, and prepregnancy BMI, which may have confounded the estimates. Also, the authors said they only considered initial ART therapy, and did not take into account patients who may have switched medications during pregnancy.

Patel said there is a need for more data on the safety and efficacy of newer HIV/AIDS medications in pregnancy. "It's truly unfortunate that pregnant people are not included in trials of new medications because it's really hard to know whether they are safe to use in pregnancy," Patel told MedPage Today. "As a research community, we have to do better."

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