title: 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.
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.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, 27599, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Betts
authors.forename: J F
authors.initials: JF
authors.lastname: Krowka
authors.forename: T B
authors.initials: TB
authors.lastname: Kepler
authors.forename: M
authors.initials: M
authors.lastname: Davidian
authors.forename: C
authors.initials: C
authors.lastname: Christopherson
authors.forename: S
authors.initials: S
authors.lastname: Kwok
authors.forename: L
authors.initials: L
authors.lastname: Louie
authors.forename: J
authors.initials: J
authors.lastname: Eron
authors.forename: H
authors.initials: H
authors.lastname: Sheppard
authors.forename: J A
authors.initials: JA
authors.lastname: Frelinger
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D003601:Cytotoxicity Tests, Immunologic; D015684:Gene Products, pol / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
chemical_list: D015684:Gene Products, pol; D015395:Histocompatibility Antigens Class I; D019713:Receptors, CCR5