Integrase Strand Transfer Inhibitors Unlikely to Cause Birth Defects in HIV-Positive Pregnant Women

By Marilynn Larkin

October 23, 2020

NEW YORK (Reuters Health) - HIV-positive pregnant women taking integrase strand transfer inhibitors (INSTIs) don't seem to be at significantly greater risk of adverse pregnancy outcomes, researchers say.

"Currently, a vast majority of women living with HIV are already receiving ART at the time of conception (>70% in France, for example), and we need to have reassuring data on the potential risk of birth defects," Dr. Jeanne Sibiude of AP-HP Hopital Louis Mourier in Colombes, France, told Reuters Health by email.

"Data on anti-integrase is important, as this class is gradually replacing other classes of ART such as protease inhibitors or non-nucleoside reverse transcriptase because they have a better tolerance profile, good effectiveness and low risk of inducing resistance," she said.

As reported in AIDS, Dr. Sibiude and colleagues analyzed birth defects and other perinatal outcomes using data from the national French Perinatal Cohort. They matched pregnant women exposed to INSTIs with pregnant women taking darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors. Participants also were matched for characteristics such as age, geographic origin, center and year of delivery.

Among 808 women exposed to INSTIs during pregnancy (raltegravir, 703; dolutegravir, 57; elvitegravir, 48), exposure at conception was not significantly associated with a higher risk of birth defects (5.7% vs. 2.9%).

However, specifically with raltegravir, a slightly higher rate of birth defects was seen in infants exposed at conception (6.7%) versus infants exposed to raltegravir later in pregnancy (2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment).

Nonetheless, when compared to controls, raltegravir exposure at conception was not significantly associated with birth defects (6.4% versus 2.3%). No neural tube defects were seen, nor was there a cluster of birth defect type. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched controls.

No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir.

Dr. Tina Yarrington, director of labor and delivery and medical director of the Positive HOPE team at Boston Medical Center, commented by email, "HIV management, both for whole woman health and to prevent vertical transmission to the newborn, hinges on medications that are effective, realistic, and tolerated even in the midst of nausea."

"We have analyzed prior data related to the risk of birth defects associated with the INSTI class and found the therapy safe and effective," she told Reuters Health. "The advantages are significant - in addition to the improved adherence with once-daily dosing, levels of INSTI medications do not change as pregnancy progresses, unlike some of the older alternative regimens."

"This study is an important contribution not only because it reinforces the safety of this medication to clinicians like us, but because it contributes to a research culture supporting these types of studies in pregnant women," Dr. Yarrington concluded.

SOURCE: AIDS, online October 8, 2020.