353 HAART Alters the Natural Evolution of the Pattern of HIV-specific Immune Responses in Subjects Starting HAART in Primary HIV Infection G. Alter*1, G. Hatzakis1, C. M. Tsoukas1, D. Rouleau2, R. P. LeBlanc1, J.-G. Baril3, H. Dion4, E. Lefebvre4, R. Thomas4, P. Côté3, J.-P. Routy1, R.-P. Sékaly5, N. F. Bernard1 1McGill Univ Hlth Ctr, Montreal, Canada; 2Ctr Hosp de l’Univ de Montreal, Canada; 3Clin Med du Quartier Latin, Montreal, Canada; 4Clin l’Actuel, Montreal, Canada; and 5Univ of Montreal, Canada
Background: HIV-specific CD8+ T-cell responses that appear early in HIV primary infection (PI) are believed to play a role in controlling viral replication, although they fail to clear virus. Host-virus interactions early in HIV infection are thought to impact on subsequent HIV course of disease.
Hypothesis: HAART alters the natural evolution of HIV-specific immune responses.
Methods: The study population included 10 subjects in PI who refused HAART. Entry into this study began 41-230 days from the estimated date of infection. For comparison, we studied subjects who started HAART before seroconversion (n = 6), in early infection (n = 11), later in the first year of infection (n = 5), and in the chronic phase of infection (n = 6). All treated subjects suppressed viremia to below 50 copies/ml of plasma. HIV-specific immune responses were assessed in longitudinal samples collected from these individuals by Interferon-gamma (IFN-gammag) ELISpot assay using, as stimuli, panels of 8-21 HLA class I restricted HIV peptides. Comparisons were made between values at baseline vs 1 yr. The one-tailed Fisher P-exact test and the Wilcoxon matched pairs test were used to assess differences in the breadth and magnitude of HIV-specific responses, respectively.
Results: All those who started HAART pre-seroconversion and 5/11 (45%) who began treatment in early PI maintained the breadth and magnitude of their HIV-specific effector activity throughout follow up (p = N.S. baseline vs 1 yr). All other subjects who began treatment in PI or in the chronic phase of infection exhibited a narrowing in the breadth and a decline in the frequency of HIV-specific effector activity (p < 0.05). Untreated subjects who followed, starting in PI, maintained both the breadth and magnitude of their HIV-specific response (p = N.S.). While treated subjects with stable responses also maintained the hierarchy of HIV peptide recognition, untreated subjects exhibited expansions and contractions with time in the frequency of cells responding to individual peptides. Only 22% of peptides were consistently recognized by untreated subjects at all times, whereas 68% of peptides tested were persistently recognized in the treated patients at all time points (p = 0.047).
Conclusion: Introducing HAART dramatically alters the pattern of immune responses to HIV. In untreated PI, host-virus interactions and adaptations are likely contributing to changes over time in the frequency of cells recognizing individual HIV peptides.
