Journal ArticleDOI
Influence of delayed viral production on viral dynamics in HIV-1 infected patients.
John E. Mittler,Bernhard Sulzer,Avidan U. Neumann,Avidan U. Neumann,Avidan U. Neumann,Alan S. Perelson +5 more
Reads0
Chats0
TLDR
It is demonstrated that it is possible to incorporate distributed intracellular delays into existing models for HIV dynamics and to use these refined models to estimate the half-life of free virus from data on the decline in HIV-1 RNA following treatment.Abstract:
We present and analyze a model for the interaction of human immunodeficiency virus type 1 (HIV-1) with target cells that includes a time delay between initial infection and the formation of productively infected cells. Assuming that the variation among cells with respect to this 'intracellular' delay can be approximated by a gamma distribution, a high flexible distribution that can mimic a variety of biologically plausible delays, we provide analytical solutions for the expected decline in plasma virus concentration after the initiation of antiretroviral therapy with one or more protease inhibitors. We then use the model to investigate whether the parameters that characterize viral dynamics can be identified from biological data. Using non-linear least-squares regression to fit the model to simulated data in which the delays conform to a gamma distribution, we show that good estimates for free viral clearance rates, infected cell death rates, and parameters characterizing the gamma distribution can be obtained. For simulated data sets in which the delays were generated using other biologically plausible distributions, reasonably good estimates for viral clearance rates, infected cell death rates, and mean delay times can be obtained using the gamma-delay model. For simulated data sets that include added simulated noise, viral clearance rate estimates are not as reliable. If the mean intracellular delay is known, however, we show that reasonable estimates for the viral clearance rate can be obtained by taking the harmonic mean of viral clearance rate estimates from a group of patients. These results demonstrate that it is possible to incorporate distributed intracellular delays into existing models for HIV dynamics and to use these refined models to estimate the half-life of free virus from data on the decline in HIV-1 RNA following treatment.read more
Citations
More filters
Journal ArticleDOI
Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques
Xia Jin,Daniel E. Bauer,Sarah Tuttleton,Sharon R Lewin,Agegnehu Gettie,James Blanchard,Craig E. Irwin,Jeffrey T. Safrit,John E. Mittler,Leor S. Weinberger,Leondios G. Kostrikis,Linqi Zhang,Alan S. Perelson,David D. Ho +13 more
TL;DR: It is demonstrated that CD8 cells play a crucial role in suppressing SIV replication in vivo and are examined using an anti-CD8 monoclonal antibody, OKT8F.
Journal ArticleDOI
Modelling viral and immune system dynamics
TL;DR: The use of mathematical modelling to interpret experimental results has made a significant contribution to the understanding of human immunodeficiency virus 1 and other viruses, such as hepatitis B virus and hepatitis C virus, that cause chronic infection.
Journal ArticleDOI
A delay-differential equation model of HIV infection of CD4(+) T-cells.
Rebecca V. Culshaw,Shigui Ruan +1 more
TL;DR: A discrete time delay is introduced to the model to describe the time between infection of a CD4(+) T-cell and the emission of viral particles on a cellular level and criteria are given to ensure that the infected equilibrium is asymptotically stable for all delay.
Journal ArticleDOI
Appropriate Models for the Management of Infectious Diseases
TL;DR: Analytical methods are used to show that ignoring the latent period or making the common assumption of exponentially distributed latent and infectious periods always results in underestimating the basic reproductive ratio of an infection from outbreak data.
Journal ArticleDOI
Mathematical analysis of delay differential equation models of HIV-1 infection
TL;DR: It is shown that when the drug efficacy is less than perfect the estimated value of the loss rate of productively infected T cells, delta, is increased when data is fit with delay models compared to the values estimated with a non-delay model.
References
More filters
Journal ArticleDOI
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection
TL;DR: Treatment of infected patients with ABT-538 causes plasma HIV-1 levels to decrease exponentially and CD4 lymphocyte counts to rise substantially, indicating that replication of HIV- 1 in vivo is continuous and highly productive, driving the rapid turnover ofCD4 lymphocytes.
Journal ArticleDOI
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
TL;DR: A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease, providing not only a kinetic picture ofAIDS pathogenesis, but also theoretical principles to guide the development of treatment strategies.
Journal ArticleDOI
Viral dynamics in human immunodeficiency virus type 1 infection
Xiping Wei,Sajal Ghosh,Maria E. Taylor,Victoria A. Johnson,Emilio A. Emini,Deutsch Paul J,Jeffrey D. Lifson,Sebastian Bonhoeffer,Martin A. Nowak,Beatrice H. Hahn,Michael S. Saag,George M. Shaw +11 more
TL;DR: Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurs after fourteen days, indicating that HIV-1 viraemia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection and replication and rapid cell turnover.
Journal ArticleDOI
HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy
TL;DR: Results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual.