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131 HIV-Specific Effector Activity in Patients at Different Stages of Primary HIV Infection
G. Alter*, N. F. Bernard, A. Merchant, C. M. Tsoukas, D. Rouleau, R. LeBlanc, P. Côté, J.-G. Baril, R. Thomas, V.-K. Nguyen, R. Sékaly, and J.-P. Routy
McGill Univ. Hlth. Ctr., Montreal, QC, Canada
Background: HIV-specific CD8+ T-cell responses appear early in HIV infection playing a role in controlling viral replication, yet they do not completely suppress viremia. Others have reported that early responses in primary infection are weaker compared with those at later stages of disease and have proposed that this may contribute to the establishment of a progressive infection.
Objective: We used the IFN-g Elispot assay to assess the magnitude and breadth of the HIV-specific CD8 T-cell effector function in a cross-section of HAART-naïve subjects in the first year of PI in comparison with chronic subjects.
Methods: Seventeen subjects within 4 months of exposure to HIV resulting in seroconversion, 11 subjects later in the first year of infection, and 20 chronically infected subjects were screened for HIV-specific effector activity. PBMCs were stimulated with a panel of 5(21 HIV peptides in an HLA class I-restricted fashion.
Results: HIV-specific responses to at least 1 peptide were detected in 94% of subjects in early PI, in all subjects in late PI, and in 90% of those in chronic infection. Of HIV peptides tested, 61 and 74% induced above background levels of IFN-gamma in early and late PI, respectively. Both PI groups had a broader response than did the chronic subjects. A significant correlation was observed between the magnitude and breadth of HIV-specific effector responses and time elapsed from exposure. Maximal breath of the HIV gene product reactivity was achieved within 2 months of exposure for responses directed at Nef and between 2 and 4 months of exposure for responses directed at Env, Gag, and reverse transcriptase (RT). No waning of the breadth of the HIV-specific response was detected in the first year of infection in this untreated cross-sectional sample. The breadth of the response directed at Gag, RT, and Nef was significantly reduced in the chronic phase of HIV infection.
Conclusions: We showed that the magnitude and breadth of the response is lower the shorter the time elapsed from exposure leading to infection. Maximal breadth of response directed at the regulatory protein Nef appeared before that directed at structural HIV proteins.
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