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Published on: July 24, 2016
Brief Report: Prenatal Antiretroviral Exposure and Concomitant Neurodevelopmental Problems Among 5-Year-Old Children
Tzy-Jyun Yao1, Joel Zhang1, Kathleen Malee2
1Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA.
Insights
Prenatal exposure to atazanavir (ATV) combined with tenofovir disoproxil fumarate/emtricitabine was linked to behavioral issues in children HIV-exposed but uninfected (CHEU). This association was specifically noted when antiretroviral therapy began during pregnancy.
Area of Science:
- Pediatric Neurodevelopment
- HIV Research
- Pharmacovigilance
Background:
- Atazanavir (ATV) is a preferred protease inhibitor for pregnant women with HIV, often co-prescribed with tenofovir disoproxil fumarate (TDF)/emtricitabine.
- Previous studies suggest prenatal ATV exposure may correlate with early neurodevelopmental challenges in HIV-exposed but uninfected children (CHEU).
Purpose of the Study:
- To investigate the association between prenatal exposure to specific antiretroviral therapy (ART) regimens and neurodevelopmental outcomes in CHEU at age 5.
- To compare behavioral, cognitive, and language functioning between CHEU exposed to TDF/emtricitabine with/without ATV versus zidovudine/lamivudine without ATV.
Main Methods:
- A prospective, US-based, multisite cohort study evaluated 585 monolingual English-speaking CHEU.
- Cognition, language, and behavior were assessed at age 5 using composite scores.
- Exploratory factor analyses identified underlying factors for neurodevelopmental domains. Linear generalized estimating equations compared factor scores between ART exposure groups, adjusting for confounders and ART initiation timing.
Main Results:
- Two underlying factors were identified: Factor 1 (cognition/language) and Factor 2 (behavior).
- No significant differences in cognitive/language factor scores were observed across ART exposure groups.
- CHEU exposed to TDF/emtricitabine with/without ATV showed worse behavioral functioning factor scores compared to those on zidovudine/lamivudine, particularly when ART initiation occurred post-conception or in the first trimester.
Conclusions:
- Prenatal exposure to TDF/emtricitabine/ATV is associated with parent-reported behavioral concerns in CHEU.
- The timing of maternal ART initiation during pregnancy may influence the observed neurodevelopmental outcomes.
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.
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