William S. Hlavacek, Carla Wofsy, Nikolaos I. Stilianakis, Daan W. Notermans, Sven A. Danner, and Alan S. Perelson

The follicular dendritic cell (FDC) network is a major site of HIV-1 accumulation in infected patients. We have used mathematical models for HIV-1 dynamics, which combine earlier models for viral and cellular dynamics with a physicochemical model for the reversible multivalent binding of virions to receptors on FDC, to analyze blood and lymphoid tissue data. We consider two questions. How long does virus persist on FDC? And to what extent does FDC-associated virus influence the dynamics of viral decay during treatment? We find that (1) a small fraction of virus may remain on FDC indefinitely, (2) potentially infectious virus is released from FDC continuously during treatment, (3) release of virus from FDC influences the entire time course of viral decay and requires us to revise upward previous model-based estimates of the rate constants for death of productively infected cells and clearance of virus, and (4) drug regimens that contain only protease inhibitors may be more effective at reducing the load of infectious virus than combinations of protease and reverse transcriptase inhibitors. These results suggest that the interaction of HIV-1 with FDC may be an important target for therapeutic intervention.