7th Conference - Abstract 209

The HIV-1-Specific CD8+ T Cell Response in Primary HIV-1 Infection

D. F. NIXON*¹, J. HU¹, J. GOLDWITZ¹, R. CHANDWANI¹, G. M. ORTIZ¹, M. LARSSON², N. BHARDWAJ², A. HURLEY¹, D. D. HO¹, and M. MARKOWITZ¹. ¹Aaron Diamond AIDS Res. Ctr., NY and ²The Rockefeller Univ., NY

After initial infection with HIV-1 there is a burst of viral replication followed by containment of plasma viremia to a lower set point level. Once this set point is reached there is an inverse correlation between the strength of HIV-1-specific CTL response and plasma load of viral RNA. As the magnitude and breadth of the HIV-1-specific CTL response at set point is related to the events in primary HIV- infection (PHI), further understanding of the magnitude and specificity of this early HIV-1-specific cellular immune response is important. We have measured the strength and breadth of HIV-1-specific CD8+ T cell responses in 38 primary HIV-1 infection (PHI) subjects in a cross-sectional study, using an enzyme linked immunoassay (ELISPOT) which measures the number of CD8+ T cells secreting IFN-g after antigenic stimulation. CD8+ HIV-1-specific responses to Env, Gag, Pol and Nef antigens were quantified on a single cryopreserved peripheral blood mononuclear cell (PBMC) sample for each subject. Plasma load of viral RNA was determined using bDNA or RT-PCR assay. CD4+ and CD8+ T cell counts were determined by routine laboratory methods. The range of days from first symptomatic illness was 12 to 121 for these PHI subjects, with a median of 38 days. We observed an inverse correlation between viral load and CD4+ T cell count, and a higher viral load in those subjects whose samples were closest to first reported symptoms. We observed a positive correlation between the strength of the HIV-1-GAG-specific CD8+ T cell response and CD4+ count (r=0.335, p=0.046). The higher the CD4+ T cell count, the greater the number of antigens recognized. The hierarchy of strength of responses was Env>Gag>Pol>Nef. There was no correlation between viral load and magnitude of total CD8+ T cell response (r=0.137, p=0.447). In conclusion, we have observed a dominance of Env-specific CD8+ T cell responses in primary HIV-1 infection, and the magnitude of the HIV-1-GAG-CD8+ T cell response is related to CD4+ count.

Key Words: CTL, HIV, Primary