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Journal of Virology, March 2001, p. 2597-2603, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2597-2603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood

Viktor Müller,1,* Athanasius F. M. Marée,2 and Rob J. De Boer2

Collegium Budapest, Institute for Advanced Study, 1014 Budapest, Hungary,1 and Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands2

Received 19 July 2000/Accepted 20 December 2000

Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. We extend previous models by also considering the large pool of virus localized in the lymphoid tissue (LT) compartment. The results indicate that the fastest time scale of HIV-1 plasma load decay during therapy probably reflects the clearance rate of LT virus and not, as previously supposed, the clearance rate of virus in plasma. This resolves the discrepancy between the clearance rate estimates during therapy and those based on plasma apheresis experiments. In the extended models plasma apheresis measurements are indeed expected to reflect the plasma decay rate. We can reconcile all current HIV-1 estimates with this model when, on average, the clearance rate of virus 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 estimates 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 results suggest that extending current HCV models with an LT compartment is not likely to affect current estimates for kinetic parameters and virus production. Estimates for treatment efficacy might be affected, however.

* Corresponding author. Mailing address: Collegium Budapest, Institute for Advanced Study, Szentháromság u. 2, 1014 Budapest, Hungary. Phone: 36 1 224 8306. Fax: 36 1 224 8310. E-mail: muller_v{at}ludens.elte.hu.

Journal of Virology, March 2001, p. 2597-2603, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2597-2603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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