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participating institutions:
Johns Hopkins University AIDS Service, New York State DOH AIDS Institute, The CORE Center, Cook County Hospital



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Impaired replication of protease inhibitor-resistant HIV-1 in human thymus [Stoddart CA et al. Nature Medicine 2001; 7: 712]:Prior studies have shown that some patients with virologic failure have persistent production of new CD4 cells, and a prior study showed that PI-resistant strains of HIV retain virulence for peripheral CD4 cells. This led to the hypothesis that these resistant strains have reduced replication capacity in the thymus. This report addresses the question by comparing the replication of wild-type versus PI-resistant HIV strains in peripheral blood mononuclear cells, thymic cultures, and human thymus implants in SCID-hu Thy/Liv mice. In thi study both types of strains replicated well in PBMC, but the PI-resistant strains had a marked reduction in replicative capacity in thymocytes. The authors conclude that this reduced replicative capacity in HIV in the thymus facilitates preservation of the CD4 cell counts in some patients who fail PI-based regimens.
Comment: This is a potentially important observation in terms of strategies for managing HIV. The attention has previously been on the paradoxical benefit of regimens with PIs which now seems explained. The application to NNRTI-based regimens is unknown.
posted 6/14/2001





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