THE ROLE OF CYTOMEGALOVIRUS IN THE INFLAMMATION ASSOCIATED WITH HIV INFECTION AND AGING
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Background Highly active antiretroviral therapy (HAART) has enabled people with HIV infection (HIV+) to live longer but has also resulted in an increase in aging-related conditions, such as frailty. Chronic inflammation is a hallmark of HAART-treated HIV infection and aging. Cytomegalovirus (CMV) infection can cause chronic inflammation and is prevalent in both HIV-infected and elderly people. CMV-specific T cells comprise 10-20% of the T cell pool, and in a recent study, T cell responses to CMV correlated with inflammatory markers. However, the relationship between CMV levels in peripheral blood mononuclear cells (PBMC) and the magnitude of T cell responses to CMV is unknown. Objectives 1) To quantify the amount of CMV DNA in PBMC and determine if this amount is related to HIV and frailty status; 2) to determine if this amount is related to T cell responses to CMV and if this relationship differs by HIV and/or frailty status. Methods Droplet digital polymerase chain reaction (ddPCR) was used to detect rare CMV DNA in PBMC from men in the Baltimore-Washington DC site of the Multicenter AIDS Cohort (MACS) study with known HIV and frailty status. Numbers of CMV-responsive T cells were compared between donors with and without detectable CMV DNA and among HIV-frailty subgroups. Results CMV DNA was detected in PBMC but levels were unrelated to HIV or frailty status. Donors with detectable CMV DNA had higher T cell responses in some cases, and donors without detectable CMV DNA had higher responses in other cases, depending on the HIV-frailty subgroup, the class of T cells (CD4 or CD8), and the specific CMV antigen. Conclusions CMV DNA was quantified in PBMC by ddPCR, and specific CMV DNAs that were or were not detected correlated with specific T cell responses to CMV. These responses may help control the amount of CMV DNA, especially responses that were greater when CMV DNA was not detected. Understanding how different CMV strains are related to the T cell response to CMV, as well as knowing who will better control CMV infection, may aid in vaccine development for CMV and in prevention of inflammation-related conditions.