Assessment of longitudinal changes in HIV-specific effector activity in subjects undergoing untreated primary HIV infection

Background: Despite the failure of HIV-specific cell-mediated immune responses to clear the virus, these cells play a critical role in the control of viral replication throughout HIV infection. Objective: To characterize the natural evolution of the HIV-specific immune response in HIV primary infection (PI). Methods: Untreated individuals, recruited in HIV PI, were monitored for the evolution of HIV-specific immune responses starting in early HIV disease. Longitudinal analysis of changes in the magnitude and breadth of HIV-specific responses to a panel of MHC class 1-restricted peptides was performed using the quantitative interferon-gamma ELISPOT assay. Results: Although immune responses were detected in all individuals at all times tested, the pattern of the immune responses differed significantly from that seen in subjects treated in PI. Untreated PI subjects exhibited dramatic changes with time in the frequency of individual HIV peptide-specific T-cell responses. In contrast HIV-specific immunity was stable in subjects treated in early PI or decreased in intensity and breadth in individuals treated later in PI. In untreated subjects the overall magnitude of HIV-specific reactivity persisted over at least 12 months whereas the number of peptides recognized declined. Conclusion: Given that a significant relationship existed between the magnitude of the HIV-specific response and viral load, it is likely that these effector cell expansions and contractions are driven by changes in antigen load. (C) 2004 Lippincott Williams Wilkins.