Brief Report: Prenatal Antiretroviral Exposure and Concomitant Neurodevelopmental Problems Among 5-Year-Old Children Who Are HIV-Exposed and Uninfected.

BACKGROUND

Atazanavir (ATV) has been a preferred protease inhibitor prescribed to pregnant women with HIV, often given with tenofovir disoproxil fumarate (TDF)/emtricitabine. Studies have reported associations of prenatal exposure to ATV with early neurodevelopmental problems among children HIV exposed but uninfected (CHEU).

SETTING

Prospective US-based multisite cohort study of CHEU.

METHODS

Monolingual English-speaking CHEU from the Surveillance Monitoring for ART Toxicities study were evaluated for cognition, language, and behavior at age 5 years. Exploratory factor analyses using 10 composite scores were performed to estimate underlying factors reflecting covariation of these domains. Mean differences of standardized factor scores were compared between CHEU exposed to TDF/emtricitabine with/without ATV versus zidovudine/lamivudine without ATV using linear generalized estimating equations, adjusting for confounders and accounting for clustering by site. Separate analyses were conducted by timing of maternal ART initiation (preconception versus postconception).

RESULTS

In total, 585 CHEU were exposed to TDF/emtricitabine with/without ATV, or zidovudine/lamivudine without ATV, and had valid composite scores. Two factors were identified, explaining 27%-88% variability of individual composite scores. Factor 1 contributed to cognitive and language domains, Factor 2 contributed to the behavioral domain. Differences in factor scores among ART exposure groups were not observed for cognition/language, but CHEU exposed to TDF/emtricitabine with/without ATV had worse behavioral functioning factor scores compared with zidovudine/lamivudine without ATV in the postconception strata, especially for those exposed to TDF/emtricitabine/ATV when ARVs were initiated in trimester 1.

CONCLUSIONS

Prenatal exposure to TDF/emtricitabine/atazanavir was associated with factor scores reflecting parent-reported behavioral concerns among CHEU whose mothers initiated ARVs during pregnancy.