Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants

Patricia A Sirois, Yanling Huo, Paige L Williams, Kathleen Malee, Patricia A Garvie, Betsy Kammerer, Kenneth Rich, Russell B Van Dyke, Molly L Nozyce, Pediatric HIVAIDS Cohort Study, William Shearer, Norma Cooper, Lynette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Doyle Patton, Richard Rutstein, Carol Vincent, Nancy Silverman, Ram Yogev, Kathleen Malee, Scott Hunter, Eric Cagwin, Andrew Wiznia, Marlene Burey, Molly Nozyce, William Borkowsky, Sandra Deygoo, Helen Rozelman, Katherine Knapp, Kim Allison, Patricia Garvie, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Sharon Nachman, Margaret Oliver, Helen Rozelman, 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, Kathleen Thoma, Ann Usitalo, Kenneth Rich, Delmyra Turpin, Renee Smith, Douglas Watson, LaToya Stubbs, Rose Belanger, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Erika Lopez, Elizabeth Willen, Toinette Frederick, Mariam Davtyan, Maribel Mejia, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio, Patricia A Sirois, Yanling Huo, Paige L Williams, Kathleen Malee, Patricia A Garvie, Betsy Kammerer, Kenneth Rich, Russell B Van Dyke, Molly L Nozyce, Pediatric HIVAIDS Cohort Study, William Shearer, Norma Cooper, Lynette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Doyle Patton, Richard Rutstein, Carol Vincent, Nancy Silverman, Ram Yogev, Kathleen Malee, Scott Hunter, Eric Cagwin, Andrew Wiznia, Marlene Burey, Molly Nozyce, William Borkowsky, Sandra Deygoo, Helen Rozelman, Katherine Knapp, Kim Allison, Patricia Garvie, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Sharon Nachman, Margaret Oliver, Helen Rozelman, 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, Kathleen Thoma, Ann Usitalo, Kenneth Rich, Delmyra Turpin, Renee Smith, Douglas Watson, LaToya Stubbs, Rose Belanger, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Erika Lopez, Elizabeth Willen, Toinette Frederick, Mariam Davtyan, Maribel Mejia, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio

Abstract

Background: This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants.

Methods: HIV-exposed, uninfected infants (age 9-15 months) enrolled in Surveillance Monitoring for Antiretroviral Therapy Toxicities, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class) and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates.

Results: As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black and 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (9% of protease inhibitor-containing regimens also included non-nucleoside reverse transcriptase inhibitors), 5% to regimens containing non-nucleoside reverse transcriptase inhibitors (without protease inhibitor) and 14% to regimens containing only nucleoside reverse transcriptase inhibitors. Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (P = 0.01).

Conclusions: These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study.

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Source: PubMed

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