Immune Reconstitution Inflammatory Syndrome Associated Kaposi Sarcoma

Abstract

People living with HIV (PLWH) with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS). Although ART is responsible for AIDS- associated Kaposi sarcoma (KS) improvement and resolution, new onset (unmasking KS-IRIS) or sudden progression of preexisting KS (paradoxical KS-IRIS) can occur after a time delay of between a few days and 6 months after the initiation or resumption of ART, even in patients with a low degree of immunocompromise. KS-IRIS incidence varies from 2.4% to 39%, depending on study design, populations, and geographic regions. Risk factors for developing KS-IRIS include advanced KS tumor stage (T1), pre-treatment HIV viral load >5 log10 copies/mL, detectable pre-treatment plasma-KSHV, and initiation of ART alone without concurrent chemotherapy. Both paradoxical and unmasking KS-IRIS have been associated with significant morbidity and mortality, and thrombocytopenia (<100,000 platelets/mm3 at 12 weeks) has been associated with death. KS-IRIS is not to be considered as ART failure, and an ART regimen must be pursued. Systemic chemotherapy for KS in conjunction with ART is recommended and, in contrast with management of IRIS for other opportunistic infections, glucocorticoids are contra-indicated. Despite our preliminary results, the place of targeted therapies in the prevention or treatment of KS-IRIS needs further assessment.