Increased CD4+ T-lymphocyte senescence fraction in advanced human immunodeficiency virus type 1 infection

Human immunodeficiency virus type 1 (HIV-1) infection is accompanied by peripheral CD4+ T-cell losses. CD4+ T-cell numbers often increase during antiviral treatment of acquired immune deficiency syndrome (AIDS), however, alterations in the CD4+ T-cell repertoire have not been completely corrected for these patients. Such individuals remain at increased risk of infection. Although senescence of the CD4+ T cells has not been adequately evaluated for advanced HIV-1 infection, hypothetically, replicative senescence could complicate therapeutic reconstitution of the CD4+ T cells in AIDS. In this study, correlates of replicative senescence, terminal restriction fragment (TRF) length and percentage short (< 5.0 kb) telomeric DNA (senescence fraction), were measured for the CD4+ T cells of HIV-1-infected patients with peripheral CD4+ T-cell counts of < 200/mm3. The results show that for advanced HIV-1 infection the TRF length of the CD4+ T cells is decreased (P < 0.01), and the senescence fraction increased (P < 0.05), when compared with uninfected controls. These findings suggest that cellular senescence may contribute to disruption of CD4+ T-cell diversity observed following the therapeutic, immunologic reconstitution of AIDS.