Population pharmacokinetic analysis of lamivudine (3TC) in HIV-exposed neonates and pediatric participants living with HIV-1 from the IMPAACT 2019 and PETITE studies
Year: 2026
Type: article
Abstract: ABSTRACT Lamivudine is a nucleoside reverse transcriptase inhibitor widely used in combination antiretroviral therapy for the treatment of human immunodeficiency virus infection. Accurate dose selection in neonates and young children remains challenging because of rapid developmental changes in renal clearance. We updated an existing pediatric population pharmacokinetic (PopPK) model, previously developed using data from 210 participants across five studies, by incorporating a maturation function and integrating pharmacokinetic data from two additional studies, IMPAACT 2019 ( n = 55) and PETITE ( n = 24, all neonates), for a total of 289 participants aged 0.0137 (~5 days) to 19.1 years. Unlike the prior model, which did not include a maturation function, the refined PopPK model incorporates a sigmoid Emax maturation function on clearance (postmenstrual age at which clearance reaches 50% of its mature [adult] value (TM50) 51.4 weeks postmenstrual age; Hill coefficient 4.81), reflecting developmental immaturity of clearance mechanisms in early life. The PopPK model retained a one-compartment structure with first-order absorption and linear elimination. Estimation of allometric exponents for body weight further improved model fit, and inter-individual and inter-occasion variability were included in clearance, volume, and absorption rate constant. Model performance was assessed using standard goodness-of-fit diagnostics and visual predictive checks, which demonstrated good agreement between observed and model-predicted concentrations across the pediatric age and weight range. In conclusion, incorporation of a maturation function on clearance successfully extended the pediatric lamivudine PopPK model to term neonates and infants, with parameter estimates remaining consistent with the original model, supporting model-informed dose selection in this understudied population.
DOI: 10.1128/aac.00701-26
Authors: Ana Carolina Conchon Costa, Yu-Wei Lin, Hardik Chandasana, Jon Collins, Adrie Bekker, Tim R. Cressey, Kristina M. Brooks, Isabelle Deprez, S. Y. Amy Cheung, Mark Bush, Rashmi Mehta, IMPAACT 2019 Team, PETITE study Team, Nicolas Salvadori, Helena Rabie, Samantha du Toit, Kanchana Than-in-at, Marisa Groenewald, Ratchada Cressey, James Nielsen, Edmund V. Capparelli, Marc Lallemant, Mark F. Cotton, Patricia Flynn, Helena Rabie, Lauren Ziemba, Shawn Ward, Yasha Rani, Iris Mustich, Anne Coletti, Ellen Townley, Dwight Yin, Barbara Heckman, Chelsea Stotz, John Moye, Sai Majji, Kelly Colsh, Sara Zabih, Rose Lagattuta, Kyle Whitson, Shahadah Bailey, Ann M. Buchanan, Cynthia Brothers
Institutions: GlaxoSmithKline (United Kingdom), Certara (United States), ViiV Healthcare (United Kingdom), Stellenbosch University, University of Liverpool, Chiang Mai University, University of Colorado Anschutz, NYU Langone Health, University of California San Diego, St. Jude Children's Research Hospital, Harvard University, Frontier Science & Technology Research Foundation, Inc., Family Health International 360, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, University of California, Los Angeles
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225753335