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The occurrence and general applicability of the CD4:8 ratio as a surrogate predictor of mortality among the oldest old have only been tested in a few longitudinal studies. Here, the predictive value of CD4:8 ratio for mortality with respect to the role of cytomegalovirus (CMV) infection was investigated. Using polychromatic flow cytometry, the CD4:8 ratio and T-cell subsets of 235 individuals aged 81.5 years or older were analyzed, and mortality data were collected after a mean period of 3.3 years. The hazard for all-cause mortality adjusted for age, comorbidity, and CMV serostatus increased 1.53-fold (95% CI: 0.94-2.51) with every increment in the CD4:8 ratio from R &lt; 1, to 1 &lt; R &lt; 5 and R &gt; 5 among women. A negative hazard ratio of 0.50 for CMV seropositivity in women indicated an apparently protective effect of this virus. In men, no associations with survival were observed. No mediation effect could be found for the CD4:8 ratio with respect to the relationship between CMV serostatus and mortality. Very elderly CMV-negative women with a R &gt; 5 experienced the highest mortality rates, independent of age and comorbidity. The associations of CMV serostatus and CD4:8 ratio with mortality seem to reflect distinct pathways mediating life span in very old humans.

CD4:8 Ratio Above 5 Is Associated With All-Cause Mortality in CMV-Seronegative Very Old Women: Results From the BELFRAIL Study