Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants

Mabel L Rice, Bret Zeldow, George K Siberry, Murli Purswani, Kathleen Malee, Howard J Hoffman, Toni Frederick, Ashley Buchanan, Patricia A Sirois, Susannah M Allison, Paige L Williams, Pediatric HIVAIDS Cohort Study (PHACS), William Shearer, Mary Paul, Norma Cooper, Lynette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Doyle Patton, Deyana Leon, Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Borkowsky, Sandra Deygoo, Helen Rozelman, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Russell Van Dyke, Karen Craig, Patricia Sirois, Marilyn Crain, Newana Beatty, Dan Marullo, Stephen Spector, Jean Manning, Sharon Nichols, Elizabeth McFarland, Emily Barr, Robin McEvoy, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Delmyra Turpin, Renee Smith, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Claudia Florez, Elizabeth Willen, Toinette Frederick, Mariam Davtyan, Maribel Mejia, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio, Mabel L Rice, Bret Zeldow, George K Siberry, Murli Purswani, Kathleen Malee, Howard J Hoffman, Toni Frederick, Ashley Buchanan, Patricia A Sirois, Susannah M Allison, Paige L Williams, Pediatric HIVAIDS Cohort Study (PHACS), William Shearer, Mary Paul, Norma Cooper, Lynette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Doyle Patton, Deyana Leon, Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Borkowsky, Sandra Deygoo, Helen Rozelman, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Russell Van Dyke, Karen Craig, Patricia Sirois, Marilyn Crain, Newana Beatty, Dan Marullo, Stephen Spector, Jean Manning, Sharon Nichols, Elizabeth McFarland, Emily Barr, Robin McEvoy, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Delmyra Turpin, Renee Smith, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Claudia Florez, Elizabeth Willen, Toinette Frederick, Mariam Davtyan, Maribel Mejia, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio

Abstract

Background: Combination antiretroviral (cARV) regimens are recommended for pregnant women with HIV to prevent perinatal HIV transmission. Safety is a concern for infants who were HIV-exposed but uninfected, particularly for neurodevelopmental problems, such as language delays.

Methods: We studied late language emergence (LLE) in HIV-exposed but uninfected children enrolled in a US-based prospective cohort study. LLE was defined as a caregiver-reported score ≤10th percentile in any of 4 domains of the MacArthur-Bates Communicative Development Inventory for 1-year olds and as ≥1 standard deviation below age-specific norms for the Ages and Stages Questionnaire for 2-year olds. Logistic regression models were used to evaluate associations of in utero cARV exposure with LLE, adjusting for infant, maternal and environmental characteristics.

Results: 1129 language assessments were conducted among 792 1- and 2-year-old children (50% male, 62% black and 37% Hispanic). Overall, 86% had in utero exposure to cARV and 83% to protease inhibitors. LLE was identified in 26% of 1-year olds and 23% of 2-year olds, with higher rates among boys. In adjusted models, LLE was not associated with maternal cARV or ARV drug classes in either age group. Among cARV-exposed 1-year olds, increased odds of LLE was observed for those exposed to atazanavir (adjusted odds ratio = 1.83, 95% confidence interval: 1.10-3.04), particularly after the first trimester (adjusted odds ratio = 3.56, P = 0.001), compared with atazanavir-unexposed infants. No associations of individual ARV drugs with LLE were observed among 2-year olds.

Conclusions: In utero cARV exposure showed little association with LLE, except for a higher risk of language delay observed in 1-year-old infants with atazanavir exposure.

Figures

Figure
Figure
Participant enrollment and language evaluations completed in the Surveillance Monitoring of ART Toxicities (SMARTT) study as of April 2011; CDI stands for MacArthur-Bates Communicative Development Inventories; ASQ for Ages and Stages Questionnaire

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Source: PubMed

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