ANTI-HIV TYPE-1 MEMORY CYTOTOXIC T-LYMPHOCYTE RESPONSES ASSOCIATED WITH CHANGES IN CD4(-CELL NUMBERS IN PROGRESSION OF HIV TYPE-1 INFECTION() T)

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 hom osexual men with incident HIV-1 infection, Study participants were sel ected who exhibited failure of T cell homeostasis, i.e., a downward in flection in CD3(+) T cells that occurs in >75% of persons 1.5 to 2.5 y ears before development of AIDS, and compared with participants who de veloped low CD4(+) T cell counts associated with possible T cell homeo stasis 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 G ag, 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 c ell homeostasis failed. Plasma HIV-1 RNA increased exponentially (1.59 -fold per year) over the 5 years preceding failure of T cell homeostas is, and there was a shift from a non-syncytium-inducing/CR5 coreceptor phenotype of HIV-1 to a syncytium-inducing/CXCR4 phenotype, regardles s of high or increasing levels of anti-HIV-1 CTLm during this time. Th ese observations suggest that decreases in CTLm and increasing virus l oad are independent factors contributing to HIV-1 disease progression.