In uence of follicular dendritic cells on HIV dynamics

In patients infected with human immunode¢ciency virus type 1 (HIV-1), a large amount of virus is associated with follicular dendritic cells (FDCs) in lymphoid tissue. To assess the in£uence of FDCs on viral dynamics during antiretroviral therapy, we have developed a mathematical model for treatment of HIV-1 infection that includes FDCs. Here, we use this model to analyse measurements of HIV-1 dynamics in the blood and lymphoid tissue of a representative patient, who was treated with a combination of HIV-1 reverse transcriptase and protease inhibitors. We show that loss of virus from FDCs during therapy can make a much larger contribution to plasma virus than production of virus by infected cells. This result challenges the notion that long-lived infected cells are a signi¢cant source of HIV-1 during drug therapy. Due to release of FDC-associated virus, we ¢nd that it is necessary to revise upward previous estimates of c, the rate at which free virus is cleared, and ̄, the rate at which productively infected cells die. Furthermore, we ¢nd that potentially infectious virus, present before treatment, is released from FDCs during therapy and that the persistence of this virus can be a¡ected by whether therapy includes reverse transcriptase inhibitors.