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Persistent immune activation in HIV-1 infection is associated with progression to AIDS
Mette D Hazenberg1, Sigrid A Otto, Birgit H B van Benthem
1Department of Clinical Viro-Immunology, Sanquin Research at CLB, Tropical Medicine and AIDS, Amsterdam, The Netherlands.
Background:
HIV-1 infection is characterized by chronic generalized CD8 and CD4 T cell hyperactivation, the biological effect of which is not understood.
Objective:
To study the relation between chronic immune activation and CD4 T cell depletion in HIV-1 infection.
Design:
Prospective cohort study among participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who have a known seroconversion date (n = 102).
Methods:
CD4 and CD8 T cell activation marker expression was analysed by FACScan before and after seroconversion (1 and 5 years after seroconversion); T cell proliferation and T cell numbers were also measured. Cox proportional hazard analyses were used to study the predictive value of these parameters for progression to AIDS.
Results:
Preseroconversion low CD4 T cell numbers or elevated levels of CD4 T cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion. Progression to AIDS was associated with loss of both CD4 and CD8 naive T cells. The predictive value of CD8 T cell activation was confirmed and, in addition, in the course of infection low CD4 T cell counts and increasing proportions of dividing CD4 T cells, dividing CD8 T cells or elevated CD4 T cell activation marker expression became independent predictors of progression to AIDS.
Conclusions:
Increased T cell activation has predictive value for HIV-1 disease progression even before seroconversion. These data support the hypothesis that persistent hyperactivation of the immune system may lead to erosion of the naive T cell pool and CD4 T cell depletion.