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HIV infection increases the risk of many types of cancer, including lymphoma. Combination antiretroviral therapy (cART) has reduced, but not eliminated, the risk of HIV-associated lymphoma. There has been a substantial shift in the subtypes of lymphoma observed in HIV-infected patients treated with cART. In this review, we will first outline these changes based on epidemiological studies and describe the impact of cART on lymphoma risk and mortality. Then, we will discuss some immunological factors that may contribute to the increased risk of lymphoma persisting after the administration of cART, including immunological non-response to therapy, chronic B-cell activation and dysfunction, T follicular helper cells, natural killer cells and altered lymphopoiesis. A better understanding of the pathophysiologic mechanisms of HIV-associated lymphoma under effective cART will inform future treatment strategies.

Loss of secretions from the salivary gland (SG) is a disease feature of Sjogren's Syndrome (SS) as well as certain viral infections, including HCV and HIV. We have found that murine cytomegalovirus (MCMV) infection of autoimmune-prone NZM2328 mice serves as a model for virus-induced exocrinopathy, displaying many SS-like disease features. Interestingly, MCMV can induce severe SG dysfunction within 2-7 days after intraperitoneal infection. MCMV replication within the gland was not directly responsible for dysfunction since NZM2328 mice secreted normally 7-14 days after low dose infection, despite high virus within the gland. Since the low dose regimen limited viral burden elsewhere in the animal, such as the spleen, SG dysfunction seemed to correspond with systemic viral load. Surprisingly, lymphocytes were not required for MCMV-induced dysfunction at day 7, including NK, T and B cells. At day 2, morphological alterations were noted in acinar epithelium and flow cytometric analysis revealed rapid changes in glandular monocytic populations. Ongoing experiments are examining a potential causal link between systemic immune responses and/or infiltrating inflammatory monocytes with morphological and functional changes within the salivary gland. Supported by NIH R01AI50072 and a Sjogren's Syndrome Foundation Student Fellowship