Natural immunity and HIV disease progression

Objective: To investigate the clinical implications of impaired levels of t he natural immunity mediated by natural killer (NK) cells and lymphokine ac tivated 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. Pati ents had active HIV infection at the time of enrolment in the study and hav e been follow-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 enrolm ent. 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 lymphoc yte count and plasma HIV RNA at enrolment, low LAK cell activity was signif icantly associated with higher risk of progression to a CD4 T lymphocyte co unt < 100 x 106 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 responsiven ess to interferon-alpha tended to be at higher risk of death (crude P = 0.0 4; adjusted P = 0.13) whereas unstimulated NK cell activity and the concent ration 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 pathogen esis of HIV infection. (C) 1999 Lippincott Williams & Wilkins.