Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men

Abstract

Context: Immunological similarities have been noted between HIV-infected individuals and older HIV-negative adults. Immunologic alterations with aging have been noted in frailty in older adults, a clinical syndrome of high risk for mortality and other adverse outcomes. Using a frailty-related phenotype (FRP), we investigated in the Multicenter AIDS Cohort Study whether progressive deterioration of the immune system among HIV-positive individuals independently predicts onset of FRP.

Methods: FRP was evaluated semiannually in 1046 HIV-infected men from 1994 to 2005. CD4 T-cell count and plasma viral load were evaluated as predictors of FRP by logistic regression (generalized estimating equations), adjusting for age, ethnicity, educational level, AIDS status, and treatment era [pre-highly active antiretroviral therapy (HAART) (1994-1995) and HAART (1996-1999 and 2000-2005)].

Results: Adjusted prevalences of FRP remained low for CD4 T-cell counts >400 cells per cubic millimeter and increased exponentially and significantly for lower counts. Results were unaffected by treatment era. After 1996, CD4 T-cell count, but not plasma viral load, was independently associated with FRP.

Conclusions: CD4 T-cell count predicted the development of a FRP among HIV-infected men, independent of HAART use. This suggests that compromise of the immune system in HIV-infected individuals contributes to the systemic physiologic dysfunction of frailty.

Figure 1

Estimated prevalences of a frailty-related phenotype (FRP) as a function of CD4 T-cell count in the MACS for fixed values of age (45 years), fixed percentage for ethnicity (80% White non Hispanic), education (52% ≥ college), and prevalence of AIDS (20%), in the pre-HAART era (1994–1995; dotted line), introduction of HAART era (1996–1999; dashed line), and established HAART era (2000–2005; plain line). The curves for the two HAART eras do not differ significantly from each other, but both are significantly different from that of the pre-HAART era (see text for Odds Ratios and p-values comparing the three different eras).