Abstract Body

Background: Immune abnormalities including T cell and macrophage/monocyte activation and immune senescence have been associated with ageassociated co-morbidities in HIV. We hypothesize that reactivation of chronic herpes viruses (specifically CMV) may drive the persistent immune changes in HIV infection- despite good control with ART. We aim to define the occurrence of CMV reactivation and its relationship to age in HIV/CMV co-infected individuals compared to CMV monoinfected individuals and to define the contribution of CMV to a CD8 dominant pro-inflammatory phenotype of aging. Methodology: We used stored samples from 20 virologically-suppressed HIV-infected and 9 sociodemographically-matched HIV-uninfected individuals enrolled in the Stanford HIV Aging Cohort (SHAC). Plasma CMV IgG antibody titer was measured, restricting our analysis to 19 of 20 HIV-infected and 8 of 9 HIV-uninfected participants who were documented to be CMV-infected. Flow cytometric analysis on peripheral blood mononuclear cells allowed phenotyping of both total immune subsets (bulk) and CMV-responsive T cells, identified by IFNγ production following CMV peptide pool stimulation (pp65 and IE-1 pools, JPT Peptide Technologies). We used Mann-Whitney tests and nonparametric Spearman correlations to evaluate p and r values. Results: HIV-infected participants (median age 54.5, median nadir and current CD4 135 and 653 cells/μL, respectively) had significantly higher CMV IgG titer than similarly aged HIV-uninfected participants (p=0.002), suggesting higher rates of CMV reactivation. Higher CMV IgG titers were also correlated with increasing age in both HIV-infected individuals (r = 0.57; p = 0.010) and in the overall study population (r = 0.44; p = 0.021). Bulk T-cell phenotyping revealed a higher percentage of terminally-differentiated effector memory CD8+ T cells (CD27- CD28- CD45RA+) in HIV-infected individuals compared to similarly aged HIV-uninfected individuals (Median 18.7% vs. 4.9%, p=0.018). HIV-infected individuals exhibited increased presence of late-stage differentiated cells staining for the pro-inflammatory cytokine, IFNγ, compared to HIV-uninfected individuals (median IFNγ+ cells/ml: 4810 vs. 333; p=0.001), which correlated positively with a higher CMV IgG response (r = 0.43, p = 0.045). IFNγ+ late-stage differentiated cells correlated positively with duration of HIV infection (r = 0.6265, p = 0.0110), while showing no significant relationship with age. Conclusions: More frequent reactivation of CMV in HIV may contribute to immune aging in HIV patients. The immune-senescent CD8+ T cells appear to be CMV specific and related to duration of HIV infection rather than age.