Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

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Abstract
It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared. A human cell that is infected with the AIDS virus HIV-1 may produce more than new viral particles over its short life span. In patients chronically infected with HIV-1, one can estimate that on average there are much less than free viral particles per productively infected cell. This suggests that the rate at which individual virus particles are cleared from the body must be fast. Most of the virus is long-lived, however, because it is trapped on follicular dendritic cells. We attempt to reconcile these seemingly contradictory observations by estimating the virion clearance rate in various organs, and the virion exchange rates between them, using a mathematical modeling approach. We find that individual virus particles are cleared rapidly from the lymphoid tissue, and that the rate at which virus is exchanged between lymphoid tissue and the blood is slow.