Session 44Poster Presentations Lymphocyte Dynamics Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall D
336 Persistent Immune Activation in HIV-1 Infection is Associated with Naive T-cell Depletion and Progression to AIDS M. Hazenberg*1, S. Otto1, B. van Benthem2, M. Roos1, R. Coutinho2, J. Lange3, D. Hamann1, M. Prins2, F. Miedema1 1Sanquin Res at CLB and Academic Med Ctr, Amsterdam, The Netherlands; 2Municipal Hlth Svc, Amsterdam, The Netherlands; and 3Academic Med Ctr, Amsterdam, The Netherlands
Background: HIV-1 infection is characterized by chronic, generalized hyperactivation of the immune system. It was previously shown that increased CD8+ T-cell activation has predictive value for disease progression, but the biological effect of hyperactivation on the immune system in HIV-1 infection is not understood.
Methods: We have studied the relation between HIV-1 induced chronic immune activation and T-cell depletion in a prospective cohort study, consisting of participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS (n = 102). In these patients, who have a known seroconversion date, we measured the level of immune activation and T-cell division at several time-points following infection and, importantly, pre-seroconversion, using CD38, HA-DR, CD70 and Ki67 monoclonal antibodies.
Results: Progression to AIDS was associated with loss of both CD4+ and CD8+ naive T-cells. We confirmed the prognostic value of low CD4+ T-cell numbers, increased HIV-1 plasma RNA, and increased activation marker expression on CD8+ T-cells for development of AIDS. Using Cox' proportional hazards analyses, and correcting for these known prognostic markers, we showed that in the course of infection, increasing proportions of dividing CD4+ and CD8+ T-cells and elevated T-cell activation marker expression on CD4+ T-cells became independent predictors of progression to AIDS. These data suggest that continuous recruitment of T-cells to the pool of rapidly proliferating and dying T-cells may cause gradual depletion of quiescent naive T-cells. Indeed, pre-seroconversion low CD4+ T-cell numbers and elevated levels of CD4+ T-cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion.
Conclusions: HIV-1 may lead to accelerated depletion of the naive T-cell pool that was already small in some patients before infection.
