Hemophagocytic lymphohistiocytosis in HIV-associated lymphoproliferative disorders

Compared to the general population the incidence of lymphoproliferative disorders (LPDs) is significantly elevated among people living with HIV (PLHIV). In high-income countries LPDs have become the most common HIV-associated cause of death among PLHIV. Lymphomas are one of the most frequent triggers of Hemophagocytic Lymphohistiocytosis (HLH), a life-threatening inflammatory syndrome that manifests as a sepsis-like syndrome thus obscuring the underlying condition and delaying its diagnosis and therapy. We performed this retrospective cohort study comprising all adult HIV-infected patients who started treatment for histologically proven LPDs between October 2013 and July 2019, to analyse risk factors, frequency and outcome of HLH among HIV-infected patients with LPDs. Of 75 patients, six (8%) presented with or developed HLH. Three patients had Hodgkin lymphoma and three had HHV-8 associated diseases. There was a significant correlation (p<0.01) between bone marrow involvement and the development of HLH. HLH was associated with lower overall survival (HR: 5.09; 95%CI: 1.53 - 16.91 p=0.008). In conclusion HLH appears to be more frequent in HIV-associated lymphomas than in HIV-negative lymphomas. The probability of developing HLH was particularly high in patients with Hodgkin lymphoma, lymphoma with bone marrow infiltration and HHV-8 associated lymphoma. Mortality was significantly increased in the presence of HLH.