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

487-M. Discordant Responses during Antiretroviral Therapy: Role for Immune Activation and T-Cell Redistribution M. Hazenberg*1, S. Otto1, D. van Baarle1, S. Kostense1, F. Wit2, J. Lange2, D. Hamann1, and F. Miedema1 1CLB/Sanquin and Landsteiner Lab. of the Academic Med. Ctr., Univ. of Amsterdam and 2 Univ. of Amsterdam, The Netherlands Background: Virus rebound during treatment with highly active anti-retroviral therapy (HAART) is usually associated with deterioration of the immune system, yet some patients maintain or improve CD4+ T-cell numbers despite virologic failure to HAART. We aimed to study the role of T cell activation in this process. Methods: Detailed longitudinal analysis of naïve, memory and effector CD4+ and CD8+ T-cell numbers and Ki-67 expression in 4 HIV-1-infected individuals during untreated HIV-1 infection, with successful HAART and during subsequent virologic failure. In parallel, HIV-1-specific CD8+ T cells were identified using tetramer staining in 2 of these patients. Results: A decline in peripheral blood CD4+ T-cell numbers was observed in those patients who had a substantial immunologic responses to rebounding virus, as reflected by high levels of immune activation and expansion of HIV-1 specific CD8+ T cells. In contrast, maintenance of CD4+ T cell numbers despite virologic failure of HAART was associated with low levels of immune activation in response to rebounding virus. Immune activation during virologic failure corresponded with baseline immune activation status. Conclusions: Changes in CD4+ T-cell numbers during virologic failure may depend on the level of immune activation that is elicited. Low reactivity to rebounding virus may preserve normal T-lymphocyte distribution over blood and tissues and thereby stable peripheral blood T-cell numbers in patients responding discordantly to HAART are seen.

©2002 9th Conference on Retroviruses and Opportunistic Infections