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

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 mere 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/CR5 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.