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

HIV-1-specific cytotoxic T cell (CTL) activity has been suggested to correl ate with protection from progression to AIDS. We have examined the relation ship between HIV-specific CTL activity and maintenance of peripheral blood CD4(+) T lymphocyte counts and control of viral load in 17 long-term surviv ors (LTSs) of HIV-1 infection. Longitudinal analysis indicated that the LTS cohort demonstrated a decreased rate of CD4(+) T cell loss (18 cells/mm(3) /year) compared with typical normal progressors (approximately 60 cells/mm( 3)/year). The majority of the LTSs had detectable, variable, and in some in dividuals, quite high (>10(4) RNA copies/ml) plasma viral load during the s tudy period. In a cross-sectional analysis, HIV-specific CTL activity to HI V Gag, Pol, and Env proteins was detectable in all 17 LTSs. Simultaneous an alysis of HIV-1 Gag-Pol, and Env-specific CTLs and virus load in protease i nhibitor-naive individuals showed a significant inverse correlation between Pol-specific CTL activity and plasma HIV-1 RNA levels (p = 0.001). Further more, using a mixed linear effects model the combined effects of HIV-1 Pol- and Env-specific CTL activity on the viral load were significantly stronge r than the effects of HIV-1 Pol-specific CTL activity alone on predicted vi rus load. These data suggest that the presence of HIV-1-specific CTL activi ty in HIV-1-infected long-term survivors is an important component in the e ffective control of HIV-1 replication.