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Simple Summary  Kaposi’s sarcoma (KS) in people living with HIV (PLHIV) occurs in the vast majority of cases when viral replication is not controlled and when CD4 immunosuppression is important. However, clinicians are observing more and more cases of KS in PLHIV with suppressed viremia on antiretroviral treatment. These clinical forms seem less aggressive, but cause therapeutic dead ends. Indeed, despite repeated chemotherapy, recurrences are frequent. Immunotherapy and specific treatment regimens should be evaluated in this population.    Abstract  Since the advent of highly effective combined antiretroviral treatment (cART), and with the implementation of large HIV testing programs and universal access to cART, the burden of AIDS-related comorbidities has dramatically decreased over time. The incidence of Kaposi’s sarcoma (SK), strongly associated with HIV replication and CD4 immunosuppression, was greatly reduced. However, KS remains the most common cancer in patients living with HIV (PLHIV). HIV physicians are increasingly faced with KS in virally suppressed HIV-patients, as reflected by increasing description of case series. Though SK seem less aggressive than those in PLHIV with uncontrolled HIV-disease, some may require systemic chemotherapy. Persistent lack of specific anti-HHV-8 cellular immunity could be involved in the physiopathology of these KS. These clinical forms are a real therapeutic challenge without possible short-term improvement of anti-HHV-8 immunity, and no active replication of HIV to control. The cumulative toxicity of chemotherapies repeatedly leads to a therapeutic dead end. The introduction or maintenance of protease inhibitors in cART does not seem to have an impact on the evolution of these KS. Research programs in this emerging condition are important to consider new strategies.

Kaposi’s Sarcoma in Virally Suppressed People Living with HIV: An Emerging Condition