Effect of Drug Efficacy and the Eclipse Phase of the Viral Life Cycle on Estimates of HIV Viral Dynamic Parameters

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Abstract
Summary:Based on a mathematical model, we analyze the dynamics of CD4+ cells, actively, latently, persistently, and defectively infected cells and plasma virus after initiation of antiretroviral therapy in 14 HIV-1-infected asymptomatic patients. By simultaneous fitting of our model to clinical data of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC)-gag RNA, proviral DNA, and CD4+ cell counts, we estimate kinetic parameters to determine the basic reproductive rate (R0) of the virus in different infected cell compartments as a measure of the replicative capacity of the virus in vivo. We find that the basic reproductive rate is larger than 1 before treatment only in actively infected cells (mean R0act ≈ 2.46) indicating that only in this compart ment the virus can maintain an ongoing infection. In latently and persistently infected cells the basic reproductive rate is considerably smaller (R0lat ≈ 0.03 and R0pers ≈ 0.008, respectively) indicating that these compartments contribute little to the total basic reproductive rate and cannot maintain an ongoing infection in absence of actively infected cells. Address correspondence and reprint requests to Sebastian Bonhoeffer, Experimental Ecology and Theoretical Biology, ETH Zurich NW, CH-8092 Zurich, Switzerland; e-mail:[email protected]: umnw.ethz.ch Manuscript received November 29, 2000; accepted March 2, 2001. © 2001 Lippincott Williams & Wilkins, Inc.