Pediatric human immunodeficiency virus infection in the modern era: A systematic review of recent advances and their implications.

Importance: Pediatric human immunodeficiency virus (HIV) infection continues to pose a significant global health burden, especially in low- and middle-income countries. Despite advances in antiretroviral therapy (ART), children living with HIV face unique clinical, developmental, and systemic challenges. Objective: To systematically review recent developments in pediatric HIV care, with a focus on treatment innovations, complications, and the transition from pediatric to adult care. Methods: A comprehensive literature review was conducted across PubMed, Scopus, EMBASE, and the World Health Organization databases, covering studies published between 2012 and 2025. Inclusion criteria focused on original research, clinical trials, and guidelines addressing pediatric ART, long-acting therapies, prevention strategies, treatment complications, and transitional care. Results: Early ART initiation was associated with improved neurodevelopment and reduced disease progression. Current pediatric ART regimens favor simplified combinations and weight-based dosing, but pharmacokinetic variability, toxicity, and adherence remain concerns. Long-acting injectable therapies, such as cabotegravir/rilpivirine and investigational agents like lenacapavir and islatravir, show promise for adolescents. Prevention of mother-to-child transmission has significantly reduced pediatric HIV incidence, largely through maternal ART and pre-exposure prophylaxis. However, stigma, poor awareness, and healthcare disparities hinder broader impact. Children on lifelong ART face increased risks of metabolic, cardiovascular, renal, and neurocognitive complications. Transitioning to adult care remains a vulnerable period with high rates of treatment disengagement. Interpretation: Advances in pediatric HIV care are substantial but uneven. Continued investment in age-appropriate therapies, psychosocial support, and implementation research is essential to close persistent gaps and ensure equitable, lifelong care for children and adolescents living with HIV.