The objective of this study is to systematically review the epidemiology and the clinical and virologic aspects of multicentric Castleman’s disease in HIV-positive patients and to evaluate treatment strategies and outcome, especially in relation to HAART administration. The authors have conducted a systematic review of the English literature for all cases of newly diagnosed multicentric Castleman’s disease in HIV-positive patients. The 25 studies which met the selection criteria included 84 HIVpositive patients with multicentric Castleman’s disease (20 pre-HAART and 64 post-HAART era). Of them, the majority (90%) were men with 33 months median time from detection of HIV-positivity to multicentric Castleman’s disease diagnosis in the HAART era. Fever and lymphadenopathy were the most common presenting symptoms and cytopenias, hypoalbuminemia, polyclonal hypergammaglobulinemia and raised C-reactive protein the most frequently revealed laboratory findings. Kaposi’s sarcoma was present in 72% of the patients and respiratory system involvement in 34%. Although the majority of cases reported were positive for human herpesvirus-8, none of the reviewed patients was found to suffer from polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Of the 48 patients on HAART, 64% were already on HAART at multicentric Castleman’s disease diagnosis, having a better immunologic profile and a lower incidence of Kaposi’s sarcoma than the 35% of patients who initiated HAART after multicentric Castleman’s disease diagnosis. Nevertheless, the two groups did not have significantly different mortality rates (30 vs. 38%). At multicentric Castleman’s disease diagnosis, a wide range of CD4 counts was recorded, suggesting that disease presentation could occur at any CD4 count. With regard to treatment, the study confirmed the high rates of response with rituximab (anti-CD20 monoclonal). Monochemotherapy seems to give short-lived responses, which require maintenance to be sustained. Polychemotherapy with CHOP has given long-term remission in a subset of patients. Other regimens used in the treatment of HIV-related multicentric Castleman’s disease were antiviral agents, immunomodulatory agents, and thalidomide. The fatality rate among HIV-related multicentric Castleman’s disease cases reviewed was 44%, significantly lower than that of HIV-negative individuals (65%), while median survival of the latter was 29 months longer than that of HIV-infected individuals. The fatality rate among pre-HAART patients was 75 vs. 29% among HAART patients. Infection, multiorgan failure, Kaposi’s sarcoma, non-Hodgkin lymphoma and progressive multicentric Castleman’s disease were the most often reported causes of death. In conclusion, multicentric Castleman’s disease is a lymphoproliferative disorder with an increasing prevalence in HIV-infected individuals. Even though life expectancy in multicentric Castleman’s disease seems to have significantly improved in the HAART era, it remains a disease with a poor prognosis and an increased incidence of non-Hodgkin lymphoma in the HIV-context. (AIDS Rev. 2008;10:25-35) Corresponding author: Eleni E. Mylona, emylon@med.uoa.gr