Factors influencing the specificity of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV/AIDS

Abstract

Introduction IRIS is a paradoxical inflammatory response in HIV/AIDS patients, occurring in 4-35% of cases after starting ART, especially in those with CD4 counts <100 cells/μL. It typically appears within 1-3 months and includes two forms: worsening of known opportunistic infections and unmasking of undiagnosed ones. Its manifestations are influenced by the interaction between ART, infections, and the host immune response. Material and methods An examination of systematic reviews and other publications in English from the past decade, utilising sources such as PubMed, Elsevier, BMJ, and the CDC and WHO. Results Elevated HIV viral loads prior to the initiation of ART, in conjunction with brief intervals between the start of OI treatment and the initiation of ART, lower pre-treatment CD4+ cell counts and a rapid increase in CD4+ cells following the commencement of ART, contribute to an increased risk of IRIS. No notable differences in gender, mode of transmission, and ART regimens were noted between the IRIS and non-IRIS patients. Region-specific IRIS includes cryptococcal meningitis (CM) and tuberculosis (TB), which are prevalent in sub-Saharan Africa and Southeast Asia; Talaromyces marneffei skin lesions have been identified in northern Thailand and Vietnam. In Latin America, CM, histoplasmosis, and paracoccidioidomycosis constitute significant fungal infections; mucocutaneous leishmaniasis has been observed in Bolivia and Peru. In the Americas and Europe, common conditions include Progressive Multifocal Leukoence-phalopathy (PML), CMV retinitis, and noninfectious issues related to IRIS. Other notable cases often involve the Mycobacterium avium complex, Kaposi's sarcoma (KS), hepatitis HBV/HCV, and, in migrants, tuberculosis (TB). Children under the age of 15 are at a higher risk of IRIS (∼26% vs. 10-20% in adults), often presenting with suppurative lymphadenitis following BCG vaccination and CMV retinitis. The decline in thymic function among the elderly alters T-regulatory responses; thus, in adults aged 15-49, a paradoxical worsening of TB and cryptococcal infections is common. For individuals over 50, IRIS is associated with atypical non-infectious conditions (such as rheumatological disorders), non-Hodgkin lymphoma, KS, and elevated mortality rates (∼25% vs. 15% in younger adults). Healthcare factors that elevate the risk of IRIS include delayed diagnosis, late ART initiation, and low CD. To minimise IRIS mortality, testing for TB and cryptococcal infections during pre-ART screening is essential in Africa and Asia; fluconazole prophylaxis is necessary in areas where cryptococcal infections are endemic; and screening for malignancies is important for older adults. Conclusions Although the fundamental immunological risk factors for IRIS are the same worldwide, its manifestations vary based on the local prevalence of opportunistic infections. This variation is also influenced by host immunity, age-related vulnerabilities, and the availability of healthcare and diagnostic resources.