Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death: evidence from a cohort of 347 HIV-infected individuals.
OBJECTIVE
To examine changes in the distribution of CD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) lymphocytes in various stages of HIV infection and the effect of these changes on disease progression.


METHODS
Expression of CD45RA+ and CD45RO+ on CD4+ lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 300 HIV-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 controls. Survival analysis was performed considering AIDS development and death as endpoints.


RESULTS
The median CD4+CD45RA+/CD45RO+ ratio was 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-infected 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 CD4+ cell counts < 200 x 10(6)/l (P < 10[-6]). When fitted in a Cox model adjusting for the total number of CD4+ cells and age a lower concentration of CD4+CD45RA+ cells was associated with an increased risk of dying. The concentration of CD4+CD45RO+ cells was not significantly associated with AIDS or death in age- and CD4+ cell count-adjusted Cox models.


CONCLUSIONS
This study confirms a selective loss of memory CD4+ cells early in HIV infection followed by increased loss of naive CD4+ cells in later stages of the infection. The loss of naive CD4+ cells seems to be important in the pathogenesis of terminal HIV infection.
Ullum
H
H
Department of Infectious Diseases, Rhima Centre, Rigshospitalet, Copenhagen, Denmark.
Lepri
A C
AC
Victor
J
J
Skinhøj
P
P
Phillips
A N
AN
Pedersen
B K
BK
D015704:CD4 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D011379:Prognosis; D012307:Risk Factors
D015704:CD4 Antigens; D017493:Leukocyte Common Antigens