LB5. Safety of In Utero Antiretroviral (ARV) Exposure: Neurologic Outcomes in HIV-Exposed, Uninfected Children

BACKGROUND: Antiretroviral therapy for pregnant women with HIV has dramatically decreased perinatal transmission of HIV, but concerns remain regarding adverse neurologic outcomes from possible mitochondrial dysfunction or other mechanisms in children exposed in utero to antiretroviral (ARV) medications. METHOD: We evaluated HIV-exposed uninfected (HEU) children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a longitudinal observational cohort study conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network. The primary outcome of interest was a “neurologic case” (microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, other neurologic conditions) as determined by clinical review blinded to ARV exposure. Log-binomial regression analysis was used to obtain adjusted relative risks (aRRs) for associations between in utero ARV exposure and neurologic case status, accounting for potential confounders including Hispanic ethnicity, tobacco use during pregnancy, and birth cohort (2011–2014 and 2015–2017 vs. <2011). To account for variable person-time follow-up within the cohort, Poisson regression models for adjusted incidence rate ratios (aIRRs) were also fitted. RESULT: Among 3,747 eligible HEU children enrolled in SMARTT (52% male, 68% Black and 31% Hispanic), 237 were diagnosed with neurologic conditions, yielding an event rate of 6.3% (95% CI: 5.6%, 7.2%). Tobacco and alcohol use during pregnancy were common (17% and 8%, respectively). The majority of children had in utero ARV exposure (87%); 60% to PI-based regimens, 16% to NNRTI-based regimens and 7% to PI + NNRTI-based regimens. In adjusted models, there was a trend towards an association between efavirenz exposure (EFV) and neurologic case status (aRR: 1.60, 95% CI: 0.99, 2.58). This association was statistically significant in sensitivity analyses restricted to children enrolled prior to or shortly after birth (aRR: 1.80, 95% CI: 1.06, 3.05), excluding children with confirmed congenital anomalies (aRR: 1.66, 95% CI: 1.02, 2.64), and accounting for person-time follow-up (aIRR: 1.55, 95% CI: 1.00, 2.76). CONCLUSION: EFV exposure during pregnancy was associated with a higher risk of neurologic abnormalities in infancy and childhood. DISCLOSURES: R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant. E. G. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends.