Disparities in Immune Fitness in HIV+ Subjects with Aging

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HIV has become a chronic disease in the US due to efficient virus control by antiretroviral therapy (ART). With that, the population over age 50 with controlled HIV is growing and already numbers >600,000 people in the US. With age these individuals experience multiple comorbidities that appear independent of HIV itself, and anecdotally some of the pathophysiology in HIV+ individuals appears as pronounced/accelerated aging. Inflammation and a decline in immune function accompany both HIV and aging, suggesting that both could potentiate and/or drive aspects of exacerbated aging in people with HIV. Persistent cytomegalovirus (CMV) infection was implicated in immune aging and age-related inflammation too, but there are significant individual variations and an incomplete understanding on how CMV is controlled with aging. Limited data suggests that the premature “aging” phenotype seen in HIV+ patients is only found in those co-infected with CMV, but the control of CMV in HIV+ subjects, particularly those over 50, remains poorly understood. Hispanic Americans experience a disproportional number of HIV infections and are also likely to acquire CMV earlier and at higher rate compared to non-Hispanic Americans. With the Hispanics bearing a large HIV and CMV burden, it is critical to understand how ethnicity affects aging with HIV and CMV. To that effect, this exploratory proposal seeks to establish whether HIV+ Hispanic Americans (HIV+HA) exhibit different (increased) systemic inflammation (cytokines and inflammatory markers) and reduced adaptive immune fitness (homeostasis at baseline and response to CMV and influenza vaccination) compared to HIV+ non-Hispanics (HIV+nHA) in the course of aging. The Aims will ask: SA1. Is Hispanic ethnicity in HIV+ subjects associated with accentuated inflammation and pronounced defects of immune homeostasis in aging? SA2. Do ethnic disparities in HIV+ subjects critically modulate immune response fitness with aging? The above experiments will provide a hypothesis-generating foundation for larger mechanistic studies of cellular and molecular inflammatory and immune pathways that may explain how Hispanic Americans handle immune aging with HIV.