Population pharmacokinetic modeling of abacavir in HIV-exposed neonates and children with HIV-1 using data from the IMPAACT 2019 and PETITE studies

Abacavir (ABC) is one of the primary HIV nucleoside reverse transcriptase inhibitors used in pediatric antiretroviral therapy, yet optimal dosing in neonates and infants is challenging because of rapid developmental changes that influence its pharmacokinetics (PK). In this work, a previously developed pediatric population pharmacokinetic (PopPK) model for ABC was refined to extend its applicability to neonates and young infants by incorporating maturation-related processes and newly available clinical data. PK data from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2019 and PETITE studies, which included term neonates (<28 days of life) and infants (<2 years), were integrated into a historical pooled data set of five pediatric studies. Multiple maturation functions and body weight scaling approaches were systematically evaluated to describe developmental changes in ABC disposition. Model performance was assessed using standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks. The final PopPK model incorporated a sigmoid Emax maturation function on oral clearance together with an age-dependent absorption rate constant, providing an accurate description of ABC PK across the full pediatric age range. The updated model successfully captured the higher systemic exposures observed in neonates and infants with immature metabolic capacity during early life. The ABC PK model supports evidence-based dosing guidance for term neonates and young infants.

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Journal
Antimicrobial Agents and Chemotherapy
Published
2026-11-03
DOI
https://doi.org/10.1128/aac.00702-26
Primary Topic
Pharmaceutical studies and practices
Type
article
Field-Weighted Citation Impact
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article

Population pharmacokinetic modeling of abacavir in HIV-exposed neonates and children with HIV-1 using data from the IMPAACT 2019 and PETITE studies

Patricia Michele Flynn, Rashmi J. Mehta, Tim Roy Cressey, Mark Fredric Cotton et al.
Antimicrobial Agents and Chemotherapy
Pharmaceutical studies and practices
article

Population pharmacokinetic modeling of abacavir in HIV-exposed neonates and children with HIV-1 using data from the IMPAACT 2019 and PETITE studies

Patricia Michele Flynn, Rashmi J. Mehta, Tim Roy Cressey, Mark Fredric Cotton, Adrie Bekker, Kelly Colsh, Isabelle Déprez, Jon W. Collins, Ann M. Buchanan, Samantha du Toit, Yasha Rani, Lauren Ziemba, Edmund V. Capparelli, Hardik Chandasana, Mark R. Bush, Anne Coletti, Iris Mustich, Helena Rabie, Won-Ho Kang, Sai Majji, Kristina M. Brooks, Ratchada Cressey, Kyle Whitson, Sara Zabih, Nicolas Salvadori, Barbara E. Heckman, Rose Lagattuta, Yu‐Wei Lin, Marisa M. Groenewald, Marc J. Lallemant, Kanchana Than-in-at, Cynthia H. Brothers, Ellen Townley, Chelsea Stotz, John H Moye, Shahadah Bailey, Shawn Ward, Dwight Yin, James Nielsen, S. Y. Amy Cheung, IMPAACT 2019 Team and PETITE Team
article en

Abstract

Abacavir (ABC) is one of the primary HIV nucleoside reverse transcriptase inhibitors used in pediatric antiretroviral therapy, yet optimal dosing in neonates and infants is challenging because of rapid developmental changes that influence its pharmacokinetics (PK). In this work, a previously developed pediatric population pharmacokinetic (PopPK) model for ABC was refined to extend its applicability to neonates and young infants by incorporating maturation-related processes and newly available clinical data. PK data from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2019 and PETITE studies, which included term neonates (<28 days of life) and infants (<2 years), were integrated into a historical pooled data set of five pediatric studies. Multiple maturation functions and body weight scaling approaches were systematically evaluated to describe developmental changes in ABC disposition. Model performance was assessed using standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks. The final PopPK model incorporated a sigmoid Emax maturation function on oral clearance together with an age-dependent absorption rate constant, providing an accurate description of ABC PK across the full pediatric age range. The updated model successfully captured the higher systemic exposures observed in neonates and infants with immature metabolic capacity during early life. The ABC PK model supports evidence-based dosing guidance for term neonates and young infants.

Antimicrobial Agents and Chemotherapy
Family Health International 360 (US), National Institutes of Health (US), St. Jude Children's Research Hospital (US), Harvard University (US), University of Liverpool (GB), University of California, Los Angeles (US), GlaxoSmithKline (United Kingdom) (GB), Stellenbosch University (ZA), University of California San Diego (US), ViiV Healthcare (United Kingdom) (GB), Certara (United States) (US), National Institute of Allergy and Infectious Diseases (US), Frontier Science & Technology Research Foundation, Inc. (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), Chiang Mai University (TH), University of Colorado Anschutz Medical Campus (US)
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Pharmaceutical studies and practices
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