IRIS and Mortality in Advanced HIV: Post-Pandemic Experience from a Single-Center Case Series

Objective: We aimed to retrospectively evaluate patients presenting with advanced human immunodeficiency virus (HIV) infection and AIDS-defining conditions following the pandemic, and to examine the occurrence of immune reconstitution inflammatory syndrome (IRIS) after antiretroviral therapy (ART) initiation. In addition, we sought to present our clinical experience. Materials and Methods: Between 2021 and 2025, we retrospectively reviewed 12 ART-naïve adults with advanced HIV infection and complete medical records. Demographic, immunological, and virological parameters, opportunistic infections, IRIS types, and treatment responses were recorded. Results: IRIS developed in all 11 patients (100%) who initiated ART. The median time to IRIS onset was 49 days (range: 20–213). Unmasking IRIS occurred in 63.6% of cases, while paradoxical IRIS accounted for 36.4%. Clinical manifestations included tuberculosis, cytomegalovirus infection, cryptococcosis, toxoplasmosis, Kaposi sarcoma, and lymphoma. Corticosteroid therapy was required in 63.6% of patients. Overall mortality was 33.3%, most frequently associated with cryptococcal meningitis, Pneumocystis jirovecii pneumonia, and Kaposi sarcoma. Conclusion: In our study, the high rates of IRIS and mortality observed among patients with advanced HIV infection and a substantial burden of AIDS-defining illnesses may represent an expected consequence of delayed presentation and increased antigen load. However, the single-center, retrospective design and the limited sample size restrict the generalizability of these findings. Therefore, prospective multicenter studies are needed to more clearly define early markers that may predict the development of IRIS. Clinical trial number: not applicable