LB5. Safety of In Utero Antiretroviral (ARV) Exposure: Neurologic Outcomes in HIV-Exposed, Uninfected Children
Session: Oral Abstract Session: Late Breaker Oral Abstracts: HIV and Antibiotic Trials
Thursday, October 4, 2018: 11:10 AM
Room: S 151-153
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 3747 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.

Claudia S. Crowell, MD MPH1, Paige Williams, PhD2, Cenk Yildirim, MS2, Russell Van Dyke, MD3, Renee Smith, PhD4, Ellen G. Chadwick, MD5, George Seage, ScD2 and Rohan Hazra, MD6, (1)Seattle Children's Hospital and University of Washington, Seattle, WA, (2)Harvard T.H. Chan School of Public Health, Boston, MA, (3)Tulane University School of Medicine, New Orleans, LA, (4)University of Illinois at Chicago, Chicago, IL, (5)Northwestern University Feinberg School of Medicine, Chicago, IL, (6)Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD


C. S. Crowell, None

P. Williams, None

C. Yildirim, None

R. Van Dyke, Giliad Sciences: Grant Investigator , Research grant .

R. Smith, None

E. G. Chadwick, Abbott Labs: Shareholder , stock dividends . AbbVie: Shareholder , stock dividends .

G. Seage, None

R. Hazra, None

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