Anti-HIV type 1 memory cytotoxic T lymphocyte responses associated with changes in CD4+ T cell numbers in progression of HIV type 1 infection

AIDS Res Hum Retroviruses. 1998 Nov 1;14(16):1423-33. doi: 10.1089/aid.1998.14.1423.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Disease Progression
  • HIV Infections / immunology*
  • HIV Infections / physiopathology
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Homeostasis
  • Humans
  • Immunologic Memory*
  • Longitudinal Studies
  • Male
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Viral Load
  • Viremia / immunology
  • Viremia / physiopathology
  • Viremia / virology