ANTI-HIV TYPE-1 CYTOTOXIC T-LYMPHOCYTE EFFECTOR ACTIVITY AND DISEASE PROGRESSION IN THE FIRST 8 YEARS OF HIV TYPE-1 INFECTION OF HOMOSEXUAL MEN

Cytotoxic T lymphocytes (CTL) may play an important role in host defense against HIV-1 infection, In this study, we examined the responses of circulating effector CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of whom were asymptomatic and had documented time since seroconversion of <8 years, CTLe responses to at least one of the four HIV-1 gene products were detected in 83% of the subjects, The magnitude and prevalence of the anti-Tat responses were significantly less than the responses to Gag, pol, and Env. Cell depletion studies indicated that the lytic activity against the HIV-1 structural proteins was mediated by CD8(+) T cells, although 30% of Env-specific lysis was mediated by CD16(+) natural killer cells, Anti-HIV-1 CTLe responses against Gag and Pol were significantly less in subjects infected for over 6 years as compared to those infected for shorter periods of time, We found no correlation, however, between anti-HIV-1 CTLe responses and either CD4(+) or CD8(+) T cell counts, rates of CD4(+) T cell loss, HIV-1 infectious viral load, use of antiviral medications, or subsequent progression to AIDS, Our results indicate that anti-HIV-1 CTLe activity is relatively stable in asymptomatic subjects infected <6 years, and is not an early marker for risk of disease progression.