Abstract
Simple SummaryKaposi sarcoma (KS) incidence has declined substantially since the advent of effective ART but it remains a frequent cancer among people living with HIV, including those on ART with a sustained undetectable HIV viral load and in late presenters. ART is responsible for KS improvement and resolution, but new onset (unmasking KS-IRIS) or sudden progression of preexisting KS (paradoxical KS-IRIS) can occur, even in patients with a low degree of immunocompromise. Both paradoxical and unmasking KS-IRIS have been associated with significant morbidity and mortality. We carried out a literature review regarding the incidence, pathogenic mechanisms, risk factors, clinical presentation, and management strategies of KS-IRIS in the ART era.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.
Highlights
People living with HIV (PLWH) and with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS) [1]
A wide spectrum of clinical manifestations can be observed during IRIS with two distinct temporal patterns recognized as (1) paradoxical IRIS, when there is a worsening or recurrence of previously treated opportunistic infections (OI) symptoms or other inflammatory auto-immune or neoplastic processes that occurs despite an earlier favorable response to therapy prior to ART, and (2) unmasking IRIS, when one or more of these events occurred following ART initiation [6,7,8,9]
A meta-analysis of six randomized trials and three observational studies involving 792 HIV-infected patients with severe Kaposi sarcoma (KS) has shown that ART plus chemotherapy with paclitaxel, liposomal doxorubicin, or daunorubicin facilitated a significant reduction of disease progression, with no differences between the three drugs [94], but no statistically significant reduction in KS-IRIS, as had been observed in one UK cohort study [95]
Summary
People living with HIV (PLWH) and with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS) [1]. French et al defines KS-IRIS as either an abrupt clinical worsening of a previously existing KS or a new presentation of a previously unknown KS in temporal association with initiation or reinitiation of ART or change to a more active regimen For each of these clinical situations, KS-IRIS occurrence is associated with a concomitant reduction of at least 1 log in the HIV-1 RNA level, or with two of the following three minor criteria: (a) a 2-fold increase in the CD4+ T-cell count after ART, (b) an increase in the immune response (KSHV-antibodies), and (c) a spontaneous resolution of disease without specific chemotherapy with continuation of ART [30]. Separating these two entities is essential, as their prognoses and therapeutic strategies differ
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