539-M. Effector/Memory CD8 T-Cell Dynamics in HIV-Infected Patients during HAART Discontinuation and Resumption

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

539-M.

Effector/Memory CD8 T-Cell Dynamics in HIV-Infected Patients during HAART Discontinuation and Resumption
G. D'Offizi*, M. Amicosante, C. Montesano, C. Gioia, S. Topino, C. Agrati, L. Pucillo, P. Narciso, and F. Poccia
Natl. Inst. for Infectious Diseases, L. Spallanzani, Rome, Italy

Background: Since supervised treatment interruption (STI) can stimulate specific anti-HIV immune response, we evaluated the CD8 T-cell specific anti-HIV immunity (anti-GAG immune response) and the CD8 T-cell effector/memory phenotypes during a cycle of treatment interruption.
Methods: We enrolled 37 patients with effective immune reconstitution under HAART (CD4 cell count >500 cells/mm³ and HIV viral load < 50 copies/mL) who suspended antiretroviral therapy because of the occurrence of side effects. A group of 25 patients completed a cycle of interruption/resumption of HAART with a median time of suspension of 57 days (range, 34-210). In the same manner, we performed a study of anti-HIV-specific response by evaluating IFN-gamma production in CD8+ T cells stimulated with selected immunodominant GAG-peptides.
Results: As expected, we observed a typical viral rebound following interruption with a return to the original viral set-point. Similarly, an increase of CD8+cell and a parallel decrease of CD4+ cell counts were observed. CD8 subsets showed, during the suspension of HAART, a significant increase of CCR7+/CD45RA- (central memory) and CCR7-/CD45RA- (effector memory). After the HAART reintroduction, all the subsets returned to baseline values. The absolute number of CD8 T-cell producing IFN-gamma in response to GAG-peptides showed an impressive increase after 1 month from HAART suspension, returning to baseline values before resumption of antiviral therapy. Interestingly, a significant increase of anti-HIV-specific response was also observed 1 month after the reintroduction of HAART.
Conclusions: In conclusion, a supervised treatment interruption/resumption does not seem to alter the kinetic of viral dynamic and the process of immune reconstitution following HAART. An unexpected stimulus of anti-HIV-specific activity was observed with the reintroduction of HAART.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections