Meconium Atazanavir Concentrations and Early Language Outcomes in HIV-Exposed Uninfected Infants With Prenatal Atazanavir Exposure

Sarah K Himes, Yanling Huo, George K Siberry, Paige L Williams, Mabel L Rice, Patricia A Sirois, Toni Frederick, Rohan Hazra, Marilyn A Huestis, Pediatric HIVAIDS Cohort Study, 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, Lourdes Richardson, 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, Sarah K Himes, Yanling Huo, George K Siberry, Paige L Williams, Mabel L Rice, Patricia A Sirois, Toni Frederick, Rohan Hazra, Marilyn A Huestis, Pediatric HIVAIDS Cohort Study, 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, Lourdes Richardson, 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

Objective: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral (ARV) quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in 1-year olds.

Methods: Pregnant women with HIV and their uninfected infants enrolled in the Surveillance Monitoring of Antiretroviral Therapy Toxicities study. Meconium ARV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Late language emergence was defined as ≥ 1 of 4 CDI scores ≤ 10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders.

Results: Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n = 93) and CDI (n = 106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower late language emergence risk (P = 0.04) and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P = 0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively).

Conclusions: Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HIV-exposed uninfected infants is required.

Conflict of interest statement

Conflicts of Interest: Authors have no other funding or conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Meconium ATV concentration by uninterrupted ATV exposure duration (from gestational week 14 through delivery) for infants exposed to TDF+ATV+ritonavir (n=125, astericks) and ATV+ritonavir (n=38, open circles). Exposure duration was determined by excluding first trimester ATV exposure (0–14 weeks), as meconium only begins to form at the beginning of the second trimester. Spearman correlations between ATV exposure duration and meconium concentration were ρ=0.212, P=0.01 overall; ρ=0.199, P=0.03 for TDF+ATV+ritonavir; and ρ=0.343, P=0.03 for ATV+ritonavir.

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