INCREASED LOSSES OF CD4-INFECTION IS RELATED TO INCREASED RISK OF DEATH - EVIDENCE FROM A COHORT OF 347 HIV-INFECTED INDIVIDUALS(CD45RA+ CELLS IN LATE STAGES OF HIV)

Objective: To examine changes in the distribution of CD4+CD45RA+ (naiv e) and CD4+CD45RO+ (memory) lymphocytes in various stages of HIV infec tion and the effect of these changes on disease progression. Design an d methods: Expression of CD45RA+ and CD45RO+ on CD4+ lymphocytes was a nalysed by flow cytometry in a prospectively followed cohort of 300 HI V-infected individuals (median follow-up time, 2.90 years; range, 0.02 -4.54 years) and in a group of 102 age-and sex-matched uninfected cont rols. Survival analysis was performed considering AIDS development and death as endpoints. Results: The median CD4+ CD45RA+/CD45RO+ ratio wa s 1.3 (25-75% quartiles, 0.9-2.4) in controls; it was increased to 1.8 (1.1-2.5) in 40 HIV-infected individuals with CD4+ cell counts > 500 x 10(6)/l (P < 0.05); it was similar at 1.4 (0.8-2.0) in 106 HIV-infec ted individuals with CD4+ cell counts of 200-500 x 10(6)/l; and it was decreased to 0.9 (0.5-1.4) in 154 HIV-infected individuals with CD4cell counts < 200 x 10(6)/l (P < 10(-6)). When fitted in a Cox model a djusting for the total number of CD4+ cells and age a lower concentrat ion of CD4+CD45RA+ cells was associated with an increased risk of dyin g. The concentration of CD4+CD45RO+ cells was not significantly associ ated with AIDS or death in age-and CD4+ cell count-adjusted Cox models . Conclusions: This study confirms a selective loss of memory CD4+ cel ls early in HIV infection followed by increased loss of naive CD4+ cel ls in later stages of the infection. The loss,of naive CD4+ cells seem s to be important in the pathogenesis of terminal HIV infection.