Natural immunity and HIV disease progression.
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.


METHODS
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.
Ullum
H
H
Department of Infectious Diseases, Rhima Centre, Rigshospitalet, Copenhagen, Denmark.
Cozzi Lepri
A
A
Aladdin
H
H
Katzenstein
T
T
Victor
J
J
Phillips
A N
AN
Gerstoft
J
J
Skinhøj
P
P
Klarlund Pedersen
B
B
D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D019562:Viral Load