Gag-Specific Cytotoxic Responses to HIV Type 1 Are Associated with a Decreased Risk of Progression to AIDS-Related Complex or AIDS

Abstract

The duration of human immunodeficiency virus (HIV-1) infection prior to the development of AIDS is variable, and for most patients the exact time of infection is not known. A group of 38 HIV-1-infected subjects was tested while asymptomatic for comparative cytotoxic lymphocyte responses to the Gag and envelope antigens of HIV-1. Twenty of the 38 patients had no detectable primary cytotoxic T lymphocyte (CTL) response to Gag, and this was associated with a relative risk of 1.89 for progression to ARC or AIDS during the subsequent 3 to 40 months of observation when compared with patients who had Gag-specific CTL activity at the beginning of the observation period. In contrast, no significant association was observed between envelope-specific cytotoxic activity and disease progression. Other patient characteristics, including CD4+ T lymphocyte counts and antibody levels to the p24gag protein, measured at the start of observation, did not correlate with disease progression during the observation period. This suggests that the anti-Gag CTL response may be protective during HIV-1 infection.

Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS.

“…Our data which indicate that Rev-and Tat-specific CTL are involved in protection from rapid disease progression are in line with earlier suggestions that CTL responses against conserved and early proteins of HIV-1 would be protective (Johnson & Walker, 1994 ;Riviere et al, 1994Riviere et al, , 1995Harrer et al, 1996 ;Van Baalen et al, 1996). Recent data obtained from studies in SIV mac -infected macaques (Hulskotte et al, 1995) indicate that in these animals also, Rev-specific CTL responses inversely correlate with disease progression (A. M. Geretti, unpublished).…”

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

“…Data also exist that show a correlation between CTL responses targeting Gag with proviral DNA, but not plasma viral RNA (24). Other studies have observed an inverse correlation between viremia and the breadth and magnitude of p24 Gag-specific CTL responses (20,(25)(26)(27). These observations alone provide strong evidence that MHC class I presentation of Gag epitopes will be essential for the effectiveness of HIV-1 vaccines and concur with the data found from macaque studies.…”

Absence of Immunodominant Anti-Gag p17 (SL9) Responses among Gag CTL-Positive, HIV-Uninfected Vaccine Recipients Expressing the HLA-A*0201 Allele

“…In both HIV-infected patients as well as SIV models, the occurrence of escape mutants is detectable within the first few months of infection, suggesting that CTLs exert considerable selective pressure on the replicating virus population (13,14). Second, the decline of CTL responses has been temporally related with the onset of overt disease in humans as well as in macaques (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Lastly, CTL activities have been detected in a subset of highly exposed uninfected individuals, and possibly correlated with transient immunoprotection (25)(26)(27)(28).…”