TY - JOUR

T1 - Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death

T2 - Evidence from a cohort of 347 HIV-infected individuals

AU - Ullum, Henrik

AU - Lepri, Alessandro Cozzi

AU - Victor, Jette

AU - Skinhøj, Peter

AU - Phillips, Andrew N.

AU - Pedersen, Bente Klarlund

PY - 1997/1/1

Y1 - 1997/1/1

N2 - 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. Design and 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 106/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 106/l; and it was decreased to 0.9 (0.5-1.4) in 154 HIV-infected individuals with CD4+ cell counts < 200 x 106/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.

AB - 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. Design and 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 106/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 106/l; and it was decreased to 0.9 (0.5-1.4) in 154 HIV-infected individuals with CD4+ cell counts < 200 x 106/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.

KW - CD4

KW - Disease progression

KW - Flow cytometry

UR - http://www.scopus.com/inward/record.url?scp=9844236467&partnerID=8YFLogxK

U2 - 10.1097/00002030-199712000-00012

DO - 10.1097/00002030-199712000-00012

M3 - Journal article

C2 - 9342070

AN - SCOPUS:9844236467

VL - 11

SP - 1479

EP - 1485

JO - AIDS

JF - AIDS

SN - 1350-2840

IS - 12

ER -