title: Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study.
abstract: 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 IFNgamma were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2+, IFNgamma+, or IL-2+IFNgamma+ 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.
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3508 AB, Utrecht, The Netherlands.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Jansen
authors.forename: Iris M
authors.initials: IM
authors.lastname: De Cuyper
authors.forename: Berend
authors.initials: B
authors.lastname: Hooibrink
authors.forename: Akke K
authors.initials: AK
authors.lastname: van der Bij
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D015683:Gene Products, gag / Q000502:physiology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D013997:Time Factors
chemical_list: D015683:Gene Products, gag