Biology and Medicine

Abstract

Pediatric and Adolescent Considerations in Antiretroviral-Induced Hepatotoxicity: Mechanisms, Risks, Monitoring and Management

Fahmida Akter, Hure Jannat Jyoti, Sophia Hossain, Sadia Afroz, Eshita Akter, Sadman Radit Aurnab, Aqib Hossain Khan and Imtiaj Hossain Chowdhury*

The scale-up of Antiretroviral Therapy (ART) has transformed pediatric and adolescent Human Immunodeficiency Virus (HIV) infection into a manageable chronic disease. Children living with HIV now initiate therapy in infancy and remain on lifelong treatment, resulting in cumulative exposure to antiretrovirals and their toxicities. Hepatotoxicity, ranging from asymptomatic transaminase elevations to severe Drug-Induced Liver Injury (DILI), represents one of the most clinically significant adverse effects of ART. Although hepatotoxicity has been extensively described in adults, pediatric populations face unique vulnerabilities due to developmental pharmacokinetics, nutritional deficiencies, coinfections, and evolving metabolic risk factors during adolescence. This review synthesizes current evidence on mechanisms of ART-related hepatotoxicity, age-specific susceptibilities, and drug class–associated risks in children and adolescents. It further explores the influence of coinfections such as hepatitis B and tuberculosis, emerging challenges including Non-Alcoholic Fatty Liver Disease (NAFLD), and the role of genetic polymorphisms in shaping hepatotoxicity risk. Current recommendations for screening, monitoring, and management are summarized, with a focus on adapting adult-derived protocols to pediatric practice. Gaps in evidence, especially in low and middle-income countries, and priorities for future research including pharmacogenomics, longitudinal studies, and non-invasive biomarkers are highlighted. Pediatric and adolescent patients with HIV represent a vulnerable population in whom hepatotoxicity is both preventable and manageable if recognized early. Optimizing monitoring strategies and developing safer regimens are essential to safeguard long-term liver health in the next generation of people living with HIV.

Published Date: 2025-09-18; Received Date: 2025-09-11