title: Anti-HIV type 1 memory cytotoxic T lymphocyte responses associated with changes in CD4+ T cell numbers in progression of HIV type 1 infection.
abstract: We investigated memory cytotoxic T lymphocyte (CTLm) responses to HIV-1 as a determinant of HIV-1 disease progression, in relation to plasma HIV-1 load and T lymphocyte numbers in a longitudinal study of 14 homosexual men with incident HIV-1 infection. Study participants were selected who exhibited failure of T cell homeostasis, i.e., a downward inflection in CD3+ T cells that occurs in >75% of persons 1.5 to 2.5 years before development of AIDS, and compared with participants who developed low CD4+ T cell counts associated with possible T cell homeostasis failure, a subject who progressed rapidly to AIDS without well-defined T cell inflection, and subjects who had long-term preservation of T cell homeostasis (nonprogressors). High CTLm responses against Gag, but not Pol or Env, soon after seroconversion were associated with a slower loss of CD4+ T cells 1-4 years after seroconversion. Anti-Env CTLm responses decreased in most subjects around the time that T cell homeostasis failed. Plasma HIV-1 RNA increased exponentially (1.59-fold per year) over the 5 years preceding failure of T cell homeostasis, and there was a shift from a non-syncytium-inducing/CCR5 coreceptor phenotype of HIV-1 to a syncytium-inducing/CXCR4 phenotype, regardless of high or increasing levels of anti-HIV-1 CTLm during this time. These observations suggest that decreases in CTLm and increasing virus load are independent factors contributing to HIV-1 disease progression.
authors.affiliation: University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: P
authors.initials: P
authors.lastname: Gupta
authors.forename: X L
authors.initials: XL
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.forename: J I
authors.initials: JI
authors.lastname: Mullins
authors.forename: S
authors.initials: S
authors.lastname: Gange
authors.forename: H
authors.initials: H
authors.lastname: Farzadegan
authors.forename: R
authors.initials: R
authors.lastname: Shankarappa
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
authors.forename: J B
authors.initials: JB
authors.lastname: Margolick
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000503:physiopathology / Q000821:virology