Human Immunodeficiency Virus Type 1-specific Cytotoxic T Lymphocyte Activity Is Inversely Correlated With HIV Type 1 Viral Load in HIV Type 1-infected Long-Term Survivors

AIDS Res Hum Retroviruses. 1999 Sep 1;15(13):1219-28. doi: 10.1089/088922299310313.

Abstract

HIV-1-specific cytotoxic T cell (CTL) activity has been suggested to correlate with protection from progression to AIDS. We have examined the relationship between HIV-specific CTL activity and maintenance of peripheral blood CD4+ T lymphocyte counts and control of viral load in 17 long-term survivors (LTSs) of HIV-1 infection. Longitudinal analysis indicated that the LTS cohort demonstrated a decreased rate of CD4+ T cell loss (18 cells/mm3/year) compared with typical normal progressors (approximately 60 cells/mm3/year). The majority of the LTSs had detectable, variable, and in some individuals, quite high (>10(4) RNA copies/ml) plasma viral load during the study period. In a cross-sectional analysis, HIV-specific CTL activity to HIV Gag, Pol, and Env proteins was detectable in all 17 LTSs. Simultaneous analysis of HIV-1 Gag-Pol, and Env-specific CTLs and virus load in protease inhibitor-naive individuals showed a significant inverse correlation between Pol-specific CTL activity and plasma HIV-1 RNA levels (p = 0.001). Furthermore, using a mixed linear effects model the combined effects of HIV-1 Pol- and Env-specific CTL activity on the viral load were significantly stronger than the effects of HIV-1 Pol-specific CTL activity alone on predicted virus load. These data suggest that the presence of HIV-1-specific CTL activity in HIV-1-infected long-term survivors is an important component in the effective control of HIV-1 replication.

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
  • Cross-Sectional Studies
  • Cytotoxicity Tests, Immunologic
  • Gene Products, pol / genetics
  • Gene Products, pol / metabolism
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV Long-Term Survivors*
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Longitudinal Studies
  • Male
  • Receptors, CCR5 / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Load

Substances

  • Gene Products, pol
  • Histocompatibility Antigens Class I
  • Receptors, CCR5