Release of virus from lymphoid tissue affects human immunodeficiency virustype 1 and hepatitis C virus kinetics in the blood

Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepat itis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. W e extend previous models by also considering the large pool of virus locali zed in the lymphoid tissue (LT) compartment. The results indicate that the fastest time scale of HIV-1 plasma load decay during therapy probably refle cts the clearance rate of LT virus and not, as previously supposed, the cle arance rate of virus in plasma. This resolves the discrepancy between the c learance rate estimates during therapy and those based on plasma apheresis experiments. In the extended models plasma apheresis measurements are indee d expected to reflect the plasma decay rate. We can reconcile all current H IV-1 estimates with this model when, on average, the clearance rate of viru s in plasma is approximately 20 day(-1), that of LT virus is approximately 3 day(-1), and the death rate of virus-producing cells is approximately 0.5 day(-1). The fast clearance in the LT compartment increases current estima tes for total daily virus production. Because HCV is produced in the liver, we let virus be produced into the blood compartment of our model. The resu lts suggest that extending current HCV models with an LT compartment is not likely to affect current estimates for kinetic parameters and virus produc tion. Estimates for treatment efficacy might be affected, however.