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Session 69 Poster Session Immunopathogenesis Issues Addressed by Therapeutic Interventions Session Time: 4:30-6:30 pm Room 4E-F

495-M. Viral- and HIV-Specific CTL Dynamics during Intermittent Antiretroviral Therapy in Chronically HIV-Infected Patients A. Oxenius1, A. McLean1, M. Fischer2, R. Hafner2, C. Schneider2, H. Joller2, D. Price1, S. Dawson1, B. Hirschel3, R. Phillips1, R. Weber2, and H. Gunthard*2 for the Swiss HIV Cohort Study 1Oxford Univ., UK and Univ. Hosp 2Zürich and 3Geneva, Switzerland Background: We wanted to evaluate whether repeated structured treatment interruptions can lower viral setpoints and whether such changes can be predicted by viral- and HIV-specific CTL dynamics. Methods: 13 chronically HIV-infected patients enrolled in the Swiss Spanish Intermittent Therapy Trial, participated in a substudy with frequent blood sampling. (Entry criteria: 1st potent antiretroviral treatment [ART], HIV plasma RNA < 50 copies/mL > 6 month, CD4 count > 300 /mL). Study design: 4 cycles of a 2-week ART-interruption (STI) followed by 8-10 weeks of retreatment. After week 40, ART was stopped > 3 month. Plasma viral load (VL) testing was done on day per cycle, and HIV-specific CTL responses by gamma-interferon ELISPOT assays were performed on day 0,8,14,22,28,56,70 per cycle. After week 40, HIV RNA and CTL were measured weekly or every 1-2 weeks thereafter. Present analysis is based on complete VL and CTL data for 64 weeks. Results: 10 of 13 patients revealed a reduction in plateau VL after STI (mean 0.7 log) and 3 showed an increase (mean 0.5 log) (p=0.045). Up rates during viral rebound decreased as rounds increased (p=0.039) but down rates after re-initiation of ART after each STI did not change significantly. Viral dynamics predicted VL plateau after treatment stop post week 40. The average chronic basic reproductive number (cR0) was highly predictive of VL plateau. In a model relating cR0 to plateau viral load, terms describing factors that decrease viral load to below that expected from STI dynamics were significant (p=0.034). Over the 4 STI cycles total spot forming cells (SFC) increased by an average of 500 SFC per round (p=0.026) and the number of responses increased by one every other round (p=0.002). Yet, changes in SFC did not correlate with changes in VL plateau. Conclusions: Viral dynamics during STIs were predictive of plateau viral load reached post STI. However, changes in plateau VL were not explained by changes in HIV-specific CTL responses, suggesting that factors other than CTL may be responsible for reductions in viral setpoints observed after 4 rounds of STIs.

©2002 9th Conference on Retroviruses and Opportunistic Infections