Effect of Age on the CD4+ T-Cell Impairment in HIV-Infected Persons Without and With cART

Background: Knowledge about HIV infection in older persons is becoming increasingly important. CD4(+) T cells are essential for protective immunity, but little is known about the effect of age on the CD4(+) T-cell impairment in HIV infection. Methods: Treatment-naive patients aged older than 50 or younger than 40 years were studied for absolute and relative frequencies of CD31(+) naive and CD31(-) naive CD4(+) T cells, central memory, effector memory, and terminally differentiated CD4(+) T cells, and compared with age-matched controls. In addition, cellular proliferation and cytokine secretion properties were determined. CD4(+) T-cell reconstitution was analyzed in older and younger patients with <350 or >= 350 CD4(+) T cells per micro-liter at initiation of combination antiretroviral tharapy (cART). Results: CD4(+) T cells of older but not younger HIV-infected patients showed age-inappropriate low levels of CD31(-) naive cells, increased levels of effector memory cells, and enhanced interferong and interleukin-17 secretion. Impaired CD4(+) T-cell composition persisted in patients who initiated cART at,350 CD4(+) T cells per microliter. In patients with CD4(+) T cells >= 350 per microliter, alterations were less pronounced and were reversible with cART. Compared with age-matched controls, total CD4(+) T-cell counts did not differ between treated younger and older HIV-infected patients. Conclusions: These data demonstrate that aging enhances the CD4(+) T-cell impairment in HIV-infected persons mainly by a loss of CD31(-) naive cells, accumulation of effector memory cells, and increased pro-inflammatory effector functions. Age-related changes in CD4(+) T-cell composition can be prevented by an early initiation of cART.