Beyond the binary: understanding inflammatory bowel disease in the context of HIV-induced immunodeficiency

The coexistence of inflammatory bowel disease (IBD) and human immunodeficiency virus (HIV) represents a clinical paradox in which immune hyperactivity coexists with persistent immunodeficiency. Improved survival with antiretroviral therapy (ART) has led to increasing co-diagnoses, creating complex diagnostic and therapeutic challenges. A comprehensive literature search of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library from inception through December 2024 was conducted, supplemented by major gastroenterology and infectious disease conference proceedings through April 2025. This review synthesizes contemporary evidence on epidemiology, immunopathogenesis, clinical presentation, and management of IBD in people living with HIV. Key themes include immune reconstitution and Th17-cell depletion, diagnostic differentiation from infectious and noninfectious mimickers, underutilization of advanced IBD therapies despite emerging safety data, bidirectional interactions between intestinal inflammation and HIV viral dynamics, and clinically relevant ART – IBD interactions requiring multidisciplinary care. Accumulating evidence supports the safe and appropriate use of immune-modulating therapies in virologically suppressed HIV-positive patients with IBD, challenging historical risk-averse approaches. Optimal management requires precision-based strategy incorporating CD4+ cell thresholds, mucosal and inflammatory biomarkers, and individualized risk stratification. Future priorities include standardized diagnostic algorithms, longitudinal registries integrating immunological and virological parameters, and improved access to advanced therapies, moving beyond the traditional autoimmunity – immunodeficiency binary.