TY - JOUR
T1 - Anti-HIV type 1 memory cytotoxic T lymphocyte responses associated with changes in CD4+ T cell numbers in progression of HIV type 1 infection
AU - Rinaldo, Jr
AU - Gupta, P.
AU - Huang, X. L.
AU - Fan, Z.
AU - Mullins, J. I.
AU - Gange, S.
AU - Farzadegan, H.
AU - Shankarappa, R.
AU - Munoz, A.
AU - Margolick, J. B.
PY - 1998/11/1
Y1 - 1998/11/1
N2 - 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-syncytiuminducing/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.
AB - 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-syncytiuminducing/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.
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U2 - 10.1089/aid.1998.14.1423
DO - 10.1089/aid.1998.14.1423
M3 - Article
C2 - 9824320
AN - SCOPUS:19244378154
VL - 14
SP - 1423
EP - 1433
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 16
ER -