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Viral Dynamics (viral + dynamics)

Distribution by Scientific Domains

Medical Sciences	70%

Selected Abstracts

Joint Inference on HIV Viral Dynamics and Immune Suppression in Presence of Measurement Errors

BIOMETRICS, Issue 2 2010
L. Wu
Summary:, In an attempt to provide a tool to assess antiretroviral therapy and to monitor disease progression, this article studies association of human immunodeficiency virus (HIV) viral suppression and immune restoration. The data from a recent acquired immune deficiency syndrome (AIDS) study are used for illustration. We jointly model HIV viral dynamics and time to decrease in CD4/CD8 ratio in the presence of CD4 process with measurement errors, and estimate the model parameters simultaneously via a method based on a Laplace approximation and the commonly used Monte Carlo EM algorithm. The approaches and many of the points presented apply generally. [source]

A Comparison Study of Models and Fitting Procedures for Biphasic Viral Dynamics in HIV-1 Infected Patients Treated with Antiviral Therapies

BIOMETRICS, Issue 1 2000
A. Adam Ding
Summary. The study of HIV dynamics is one of the most important developments in recent AIDS research. It has led to a new understanding of the pathogenesis of HIV infection. But, although important findings in HIV dynamics have been published in prestigious scientific journals in the last 5 years, the model-fitting procedures used in these publications have not been studied in any detail. In this paper, we evaluate the performance of four model-fitting procedures proposed and used in biphasic HIV dynamic data analysis via extensive Monte Carlo simulations. We propose some guidelines for practitioners to select an appropriate method for their own data analysis. Real data examples from an AIDS clinical trial are provided as illustrations. [source]

Viral dynamics and response differences in HCV-infected African American and white patients treated with IFN and ribavirin

HEPATOLOGY, Issue 6 2003
Jennifer E. Layden-Almer
Studies have suggested that African American patients infected with hepatitis C virus (HCV) do not respond as well to treatment with interferon (IFN) as white patients. Here we analyzed the difference in the viral kinetic response between genotype 1 HCV-infected African American patients (n = 19) and white patients (n = 16). Patients were treated with 10 mIU IFN-,2b daily with or without ribavirin for 1 month followed by 3 mIU IFN-,2b 3 times a week with ribavirin. The kinetic parameters (,, treatment effectiveness at inhibiting virion production; ,, loss rate of virus-producing cells; c, clearance rate of free virions; ,, delay until viral decline starts) were estimated from the viral load decay profiles using a previously described mathematical model. Differences in early kinetic parameters and viral negativity frequencies at weeks 4, 12, and 48 were compared. Ribavirin did not appear to enhance any of the viral kinetic parameters, although this may have been due to the high dose of IFN used. African American patients exhibited significantly (P = .005) lower drug effectiveness (88.6% vs. 98.2%) compared with white patients, accounting for a 0.8 log lower HCV RNA decrease in the first 24 hours of treatment. Significant differences (P = .006) were also noted for ,. There was no correlation between any of the viral kinetic parameters and either age, body mass index (BMI), or genotype 1 subtype. No patient achieved viral negativity at weeks 4, 12, or 48 without an , greater than 90%. The mean viral decline and viral negativity rates were statistically different between the two races; however, when controlling for treatment effectiveness, these differences were no longer apparent. In conclusion, the failure of IFN response in African American patients infected with genotype 1 HCV is in part due to an impaired ability to inhibit viral production. [source]

Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells,

HEPATOLOGY, Issue 3 2010
Avidan U. Neumann
Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B. The antibody HBV-17 recognizes a conformational epitope, whereas antibody HBV-19 recognizes a linear epitope on the HBsAg. The kinetic profiles of the decline of serum HBV DNA and HBsAg revealed partial blocking of virion release from infected cells as a new antiviral mechanism, in addition to acceleration of HBV clearance from the circulation. We then replicated this approach in vitro, using cells secreting HBsAg, and compared the prediction of the mathematical modeling obtained from the in vivo kinetics. In vitro, HepeX-B treatment of HBsAg-producing cells showed cellular uptake of antibodies, resulting in intracellular accumulation of viral particles. Blocking of HBsAg secretion also continued after HepeX-B was removed from the cell culture supernatants. Conclusion: These results identify a novel antiviral mechanism of antibodies to HBsAg (anti-HBs) involving prolonged blocking of the HBV and HBsAg subviral particles release from infected cells. This may have implications in designing new therapies for patients with chronic HBV infection and may also be relevant in other viral infections. (HEPATOLOGY 2010;) [source]

Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus,

HEPATOLOGY, Issue 3 2009
Hussein Hassan Aly
We developed an in vitro system that can be used for the study of the life cycle of a wide variety of blood-borne hepatitis C viruses (HCV) from various patients using a three-dimensional hollow fiber culture system and an immortalized primary human hepatocyte (HuS-E/2) cell line. Unlike the conventional two-dimensional culture, this system not only enhanced the infectivity of blood-borne HCV but also supported its long-term proliferation and the production of infectious virus particles. Both sucrose gradient fractionation and electron microscopy examination showed that the produced virus-like particles are within a similar fraction and size range to those previously reported. Infection with different HCV strains showed strain-dependent different patterns of HCV proliferation and particle production. Fluctuation of virus proliferation and particle production was found during prolonged culture and was found to be associated with change in the major replicating virus strain. Induction of cellular apoptosis was only found when strains of HCV-2a genotype were used for infection. Interferon-alpha stimulation also varied among different strains of HCV-1b genotypes tested in this study. Conclusion: These results suggest that this in vitro infection system can reproduce strain-dependent events reflecting viral dynamics and virus-cell interactions at the early phase of blood-borne HCV infection, and that this system can allow the development of new anti-HCV strategies specific to various HCV strains. (HEPATOLOGY 2009.) [source]

Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia,

HEPATOLOGY, Issue 4 2008
Maura Dandri
Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus. (HEPATOLOGY 2008.) [source]

The half-life of hepatitis B virions,

HEPATOLOGY, Issue 5 2006
John M. Murray
The virion half-life of hepatitis B virus (HBV) is currently estimated at approximately 1 day. This estimate has been obtained from drug perturbation experiments with reverse transcriptase inhibitors. However, the analyses of those experiments have not considered the export of virions produced from preformed mature DNA-containing HBV capsids in infected cells. Data from 3 acutely infected chimpanzees indicates that there is approximately 10-fold more total intracellular HBV DNA than HBV DNA in blood, and therefore the half-life of virions for chimpanzees during acute infection is 10-fold shorter at 3.8 hours than the half-life associated with export of total intracellular HBV DNA. Mathematical model simulations duplicating the viral dynamics observed in drug perturbation experiments suggest a half-life of at most 4.4 hours for HBV virions in chronically infected humans, significantly shorter than current estimates, but consistent with the half-lives of virions for hepatitis C virus and HIV. This faster turnover of HBV in blood indicates a correspondingly higher replication rate and risk of mutation against hepatitis B antiviral therapy. In conclusion, we find the half-life of HBV virions is approximately 4 hours, significantly shorter than current estimates of 1 day. This new value is consistent with virion half-life estimates for HIV and hepatitis C virus. (HEPATOLOGY 2006;44:1117,1121.) [source]

Predicting the response to 48-week combination therapy with peginterferon ,-2b plus ribavirin from the estimated HCV RNA load index after negative serum change in genotype 1b hepatitis C patients

HEPATOLOGY RESEARCH, Issue 6 2009
Keiji Tsuji
Aim:, We estimated viral dynamics after serum hepatitis C virus (HCV) RNA became negative and assessed the relation between the estimated viral load at the end of treatment (EVE) index and the response to the combination therapy with peginterferon ,-2b plus ribavirin. Methods:, Patients with chronic HCV, genotype 1b, and a high viral load were treated with this combination therapy for 48 weeks, and serum HCV RNA was measured frequently during the treatment period. In the patients showing an end-of-treatment response (ETR), the viral load profile from the start of treatment until serum HCV RNA became negative was expressed by an approximate curve. Then the EVE index was calculated by using the expression obtained from the curve, and differences between the sustained virologic response (SVR) and relapse groups were investigated. Results: The SVR rate increased as the EVE index became lower, and the EVE index was significantly lower in the SVR group than in the relapse group. The SVR rate was higher for those in whom the EVE index was below the cut-off point. Conclusion:, Prediction of SVR and relapse from the EVE index is more useful than prediction from viral dynamics at the time when HCV RNA becomes negative or when HCV RNA shows a decrease of 2-log or more. [source]