Central nervous system is a very rare site of Kaposi’s sarcoma in acquired immunodeficiency syndrome. Kaposi’s sarcoma, a neoplasm of endothelial origin, occurs mainly in the skin, but can involve many tissues, especially in patients with a poor immunity. Combination antiretroviral therapy, highly active against human immunodeficiency virus type-1, has caused a dramatic reduction of cutaneous and visceral involvements. No report of central nervous system localization of Kaposi’s sarcoma is described since the introduction of combination antiretroviral therapy in the late 90’s. A 42 year-old Caucasian man affected by human immunodeficiency virus type-1 infection treated with combination antiretroviral therapy and showing relatively preserved immunity with low viral load presented gingival squamous cell carcinoma and visceral (lungs and lymph nodes) Kaposi’s sarcoma. Chemotherapy and radiotherapy were performed with improvement of both neoplasms. Afterwards, a magnetic resonance imaging showed focal lesions of the brain. Despite new chemotherapy and radiotherapy the patient died. Histology after autopsy revealed brain lesions due to Kaposi’s sarcoma with the detection of Human Herpesvirus 8 on tissue samples. This is the first report in the combination antiretroviral therapy era of a very rare complication of Kaposi’s sarcoma, such as that of brain localization, in a patient with a relatively good control of human immunodeficiency virus infection. Therefore, Kaposi’s sarcoma should be considered in differential diagnosis with other intracranial mass lesions that can occur in human immunodeficiency virus infected-patients focusing the issue of appropriate treatment for central nervous system involvement.

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29–52), median CD4 and CD8 count 150 (15–158) and 973 (354–1250) cell/mm³, respectively; median JCV-DNA and HIV-RNA in CSF/plasma pairs 9.540/1.503 cps/mL and 2.230/619 cp/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy.