15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1001)

N Vrisekoop, A B de Boer, S A Otto, J A M Borghans, K Tesselaar, F Miedema
Sanquin Research Landsteiner Lab and Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

BACKGROUND: Although CD4 helper T cells are thought to play an important role in orchestrating the immune response against HIV, they might also provide a fertile milieu for viral replication and evolution due to their unique ability to be activated and infected by the same pathogen.

METHODS: Sequence analysis and phylogenetic reconstructions were performed on replication-competent virus induced by HIV antigens and on proviral DNA from purified virus-specific cells. Both HAART-controlled and viremic subjects were studied.

RESULTS: HIV-specific CD4 cells contain a diverse collection of viral variants that are distinct from the species found in the general pool of CD4 T cells. The virus present in HIV-specific CD4 T cells continues to evolve even in patients who initiated effective antiretroviral treatment shortly after infection. Mathematical modeling based on these findings suggests that boosting HIV-specific CD4 T cell frequency by vaccination or structured treatment interruption could actually increase viral load and decrease functional help.

CONCLUSIONS: Although drug treatment slows the evolutionary clock, it does not stop it. The ability of HIV-specific CD4 T cells to serve as a distinct reservoir for HIV growth and evolution suggests that therapies aimed solely at augmenting HIV-specific CD4 T cell responses should be undertaken with caution.

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MoOrA1001

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