IRIS in HIV — DTM&H MCQ

Correct answer: A — Immune reconstitution inflammatory syndrome (IRIS)

The correct answer is A, immune reconstitution inflammatory syndrome (IRIS). This man has advanced immunosuppression (CD4 180) and, within two weeks of starting ART, develops fever, lymphadenopathy and paradoxical worsening of a pre-existing Kaposi sarcoma lesion, the classic pattern of paradoxical IRIS, where recovering immune function drives an exaggerated inflammatory response against persistent HHV-8 antigen rather than true tumour progression. BHIVA guidance describes paradoxical IRIS as worsening of a partially treated or known condition after starting ART, typically in the first weeks to months, with low baseline CD4 count and high pathogen burden as key risk factors, both present here. IRIS is a clinical diagnosis of exclusion based on this temporal pattern once other causes are considered. Why the other options are wrong: B. ART failure requiring regimen switch: virological or immunological failure develops over months on an established regimen with rising viral load, not two weeks into a new one. C. New opportunistic infection: unmasking IRIS can reveal a subclinical infection, but the stem describes worsening of the known KS lesion itself, the paradoxical pattern, not a distinct new infectious process. E. Drug hypersensitivity to ART: hypersensitivity reactions present as rash or systemic toxicity temporally linked to the drug, not focal deterioration of a pre-existing malignancy with lymphadenopathy. D. Progression of untreated HIV: the patient is now on effective ART, so untreated progression cannot explain deterioration coinciding precisely with immune recovery after treatment start. Key point: Fever with worsening of a known HIV-associated lesion within weeks of starting ART in a patient with a low baseline CD4 count is paradoxical IRIS, driven by immune recovery rather than treatment failure or new disease.

Reference: British HIV Association (BHIVA) guidelines on the management of opportunistic infection in people living with HIV: investigation and management of pyrexia of unknown origin, 2023 (HIV Medicine 2023), section on paradoxical and unmasking IRIS. https://onlinelibrary.wiley.com/doi/10.1111/hiv.13558