TY - JOUR

T1 - Natural immunity and HIV disease progression

AU - Ullum, H

AU - Cozzi-Lepri, A

AU - Aladdin, H

AU - Katzenstein, T

AU - Victor, J

AU - Phillips, A N

AU - Gerstoft, J

AU - Skinhøj, P

AU - Klarlund Pedersen, B

PY - 1999/4/1

Y1 - 1999/4/1

N2 - OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1.DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years.METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death.RESULTS: In unadjusted analysis and after adjustment for age, CD4 T lymphocyte count and plasma HIV RNA at enrolment, low LAK cell activity was significantly associated with higher risk of progression to a CD4 T lymphocyte count < 100 x 10(6) cells/l (crude P = 0.001; adjusted P = 0.04) and to death (crude P = 0.0002; adjusted P = 0.02). Patients with low NK cell responsiveness to interferon-alpha tended to be at higher risk of death (crude P = 0.04; adjusted P = 0.13) whereas unstimulated NK cell activity and the concentration of NK cells were of no prognostic value for patients in this cohort.CONCLUSIONS: The present study suggests that low LAK cell activity and low NK cell responsiveness to interferon-alpha may be important in the pathogenesis of HIV infection.

AB - OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1.DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years.METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death.RESULTS: In unadjusted analysis and after adjustment for age, CD4 T lymphocyte count and plasma HIV RNA at enrolment, low LAK cell activity was significantly associated with higher risk of progression to a CD4 T lymphocyte count < 100 x 10(6) cells/l (crude P = 0.001; adjusted P = 0.04) and to death (crude P = 0.0002; adjusted P = 0.02). Patients with low NK cell responsiveness to interferon-alpha tended to be at higher risk of death (crude P = 0.04; adjusted P = 0.13) whereas unstimulated NK cell activity and the concentration of NK cells were of no prognostic value for patients in this cohort.CONCLUSIONS: The present study suggests that low LAK cell activity and low NK cell responsiveness to interferon-alpha may be important in the pathogenesis of HIV infection.

KW - CD4 Lymphocyte Count

KW - Disease Progression

KW - HIV Infections

KW - HIV-1

KW - Humans

KW - Immunity, Innate

KW - Killer Cells, Lymphokine-Activated

KW - Killer Cells, Natural

KW - Viral Load

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 10203380

VL - 13

SP - 557

EP - 563

JO - AIDS

JF - AIDS

SN - 1350-2840

IS - 5

ER -