Review Article

Preventable Mortality in Advanced HIV Disease in the Era of Universal ART: A Narrative Review

Abstract

The widespread adoption of universal antiretroviral therapy has transformed the global HIV response and led to substantial reductions in HIV-related mortality. However, advanced HIV disease continues to contribute disproportionately to deaths, even in settings with high treatment coverage. This narrative review examines preventable mortality among individuals presenting with or returning to care with advanced HIV disease in the era of universal ART, with a focus on clinical, programmatic, and structural determinants. Drawing on peerreviewed literature, global guidelines, and major cohort studies, the review synthesizes evidence on the epidemiology of advanced HIV disease, pathways to early mortality, and the predominant role of opportunistic infections, particularly tuberculosis and cryptococcal disease. Despite the availability of effective diagnostics, prophylactic interventions, and WHO-recommended packages of care, implementation remains inconsistent. Gaps in service integration, delayed diagnosis, weak accountability, and limited prioritization of advanced disease within HIV programs continue to undermine outcomes for the most vulnerable patients. The persistence of preventable mortality highlights a disconnect between scientific advances and health system delivery. Universal ART alone is insufficient to eliminate HIV-related deaths without targeted, high-intensity care for individuals with severe immunosuppression. Reducing mortality will require reframing advanced HIV disease as a health system emergency and ensuring full implementation of comprehensive, evidence-based care.