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Session 72 Poster Session Treatment Interruption Session Time: 4:30-6:30 pm Room 4E-F

538-M. HIV-Specific CTL Responses do not Prevent Early Viral Rebound and Immunological Deterioration after STI in Chronic HIV Infection J. van Lunzen*1, N. Frahm1, J. Schmitz3, M. Kuroda3, B. Walker2, H. J. Stellbrink1, and M. Altfeld2 1Univ. Hosp. Eppendorf, Hamburg, Germany; 2Partners AIDS Res. Ctr., Massachusetts General Hosp., Boston; and 3Beth Israel Deaconess Med. Ctr., Boston, MA Background: It is questionable whether viral replication can be controlled by STI-induced CTL responses in chronic HIV infection. Our objective was to corellate CTL responses with viral replication after STI in patients with chronic HIV infection and sustained suppression of viremia. Methods: Preselected patients (n=15) underwent STI if they met the following criteria: sustained suppression of viremia (<25 copies/mL for 12-23 months) in peripheral blood (PB) and CSF; no or minimal residual viral replication in lymph nodes (LN); and a CD4/CD8 ratio >1,0 during HAART. Viral replication kinetics and immunological parameters of T-cell activation (CD69, CD25, CD38, HLA-DR, Ki67) were assessed at frequent intervals. The frequency of HIV-specific cytotoxic T cells (CTL) was studied by ELISPOT, intracellular cytokine staining (ICS), and tetramer staining. Results: All patients experienced a viral rebound to pre-therapy levels (median 4 weeks) after STI which was associated with pronounced T-cell activation and a re-inversion of the CD4/CD8 ratio due to increased CD8+ T-cell proliferation. T-cell turnover increased after STI and the frequency of CTL followed the same kinetics as the viral load increase without altering the virological set point level. The number of recognized epitopes did not change significantly over time but CTL responses to individual epitopes were preserved in LN which appeared later in PB during STI. Overall the magnitude of CTL responses was more pronounced in LN compared with PB. An identical pattern of CTL responses was observed using ELISPOT, ICS, and tetramer staining. The response of CD4+ T cells was more heterogenous with a lack of responsiveness in representative cases at peak of viremia. The reintroduction of HAART in 10 cases resulted in a rapid control of viral replication which was associated with a marked decrease of CTL frequency in PB. Conclusions: In chronic HIV infection, STI leads to a viral rebound which is associated with T-cell activation and proliferation despite the presence of HIV-specific CTL, predominantly located in LN. These data suggest that the quality and magnitude of CTL responses remain unaffected by HAART and subsequent STI in chronic HIV infection.

©2002 9th Conference on Retroviruses and Opportunistic Infections