Perinatal and early infant outcomes after first-versus second-generation integrase strand transfer inhibitor use in...

Integrase strand transfer inhibitors (INSTIs) are first-line antiretroviral medications used in pregnancy. Pre-clinical research suggests adverse effects in human stem cells associated with second- versus first-generation INSTIs. We compared perinatal and early infant outcomes after exposure to first- versus second-generation INSTIs.

Data were taken from the Canadian Perinatal HIV Surveillance Program. Infants born between January 1, 2010, and December 31, 2023, with in utero INSTI exposure were included. Univariate analysis compared perinatal and early infant outcomes between first- and second-generation INSTI exposures. Multivariable logistic regression was completed to identify independent associations between INSTI class and perinatal outcomes.

A total of 1160 infants were included: 433 exposed to first-generation INSTIs and 727 to second-generation. There was a non-significant finding of fewer small-for-gestational-age (SGA) infants with exposure to second-generation INSTIs (odds ratio [OR] = 0.75; 95% confidence interval [CI] = 0.55-1.01, p = 0.058), which remained non-significant in multivariable analysis (OR = 0.72, 95% CI = 0.49-1.07, p = 0.105). There was a non-significant finding of increased preterm births with exposure to second-generation INSTIs (OR = 1.40, 95% CI = 0.97-2.00, p = 0.070), which remained non-significant in multivariable analyses (OR = 1.01, 95% CI = 0.62-1.66, p = 0.962). There was a non-significant increase in infant deaths in the second-generation INSTI group compared to the first-generation group (6 vs. 0, p = 0.089). No differences were observed in HIV transmission (p = 0.208).

There were no significant associations between second-generation INSTIs and adverse perinatal outcomes compared to first-generation INSTIs. These findings support the ongoing use of second-generation INSTIs in pregnancy with continued careful surveillance of perinatal outcomes.