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 Blood, 15 February 2006, Vol. 107, No. 4, pp. 1427-1433.
Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-07-2907.

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IMMUNOBIOLOGY

Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study

Christine A. Jansen, Iris M. De Cuyper, Berend Hooibrink, Akke K. van der Bij, Debbie van Baarle, and Frank Miedema

From the Department of Clinical Viro-Immunology, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; the Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; the Department of HIV and STI (Sexually Transmitted Infection) Research, Cluster of Infectious Diseases, Municipal Health Service, University of Amsterdam, Amsterdam, The Netherlands; and the Department of Immunology, University Medical Center, Utrecht, The Netherlands.

The causal relationship between HIV-specific CD4+ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4+ T cells were analyzed in long-term asymptomatic individuals (LTA; n = 6) and progressors to AIDS (n = 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4+ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gag-specific CD4+ T cells producing IL-2 or IFN{gamma} were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2+, IFN{gamma}+, or IL-2+IFN{gamma}+ CD4+ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4+ T-cell responses, rather than HIV-specific CD4+ T-cell responses controlling HIV plasma viral load.


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