Abstract：
BACKGROUND:Patients infected with hepatitis C virus (HCV) who respond to treatment with interferon-alpha plus ribavirin exhibit biphasic or triphasic viral load decreases. While the rapid first phase is indicative of the effectiveness of therapy in blocking viral production (epsilon), the slope of the final phase (lambda), that is, the second phase in biphasic decreases and the third phase in triphasic decreases, depends on the infected cell loss rate (delta). In standard models, lambda is approximately epsilondelta when the viral clearance rate c>delta, as has been previously estimated. METHODS:The relationship among epsilon, delta, lambda and the baseline fraction of HCV-infected hepatocytes (pi) was investigated in a model that included proliferation of hepatocytes. RESULTS:We found that lambda was not proportional to epsilon, but rather obeyed a complex relationship that could lead to dramatic increases in estimates of delta as epsilon increased. In particular, when epsilon<99%, lambda moderately underestimated delta in patients with a small pi, whereas delta might be up to 10-fold larger than lambda in patients with a large pi. Interestingly, when epsilon>99%, delta approximately lambda regardless of pi. CONCLUSIONS:Our results indicated that in patients undergoing therapy who achieved a 2 log(10) reduction in viral load (epsilon<99%), previously estimated delta values might represent only a minimal estimate of the infected cell loss rate. Moreover, combining interferon-alpha with new antiviral agents to achieve epsilon>99% should allow for a more accurate estimate of delta in HCV RNA kinetic studies. This might be important when using viral kinetics to estimate the effect of the immune response on viral elimination and the attainment of sustained virological response.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Dahari H,Shudo E,Cotler SJ,Layden TJ,Perelson ASsubject
Has Abstractpub_date
2009-01-01 00:00:00pages
459-64issue
3eissn
1359-6535issn
2040-2058journal_volume
14pub_type
杂志文章abstract：:Clinical research has indicated that the use of nucleoside reverse transcriptase inhibitor (NRTI) and HIV protease inhibitor (PI) therapy is associated with a risk of long-term toxicity syndromes, and that the aetiopathogenesis of these adverse effects is independent of the antiretroviral effects of these drugs. In re...
journal_title：Antiviral therapy
pub_type： 杂志文章,评审
doi：
更新日期：2001-09-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,随机对照试验
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abstract：BACKGROUND:Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS:A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n ...
journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2008-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,多中心研究
doi：
更新日期：2005-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
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journal_title：Antiviral therapy
pub_type： 杂志文章
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journal_title：Antiviral therapy
pub_type： 杂志文章
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journal_title：Antiviral therapy
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2003-04-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2007-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2006-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 临床试验,杂志文章
doi：
更新日期：2005-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
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更新日期：2020-11-19 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：10.3851/IMP2326
更新日期：2013-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,多中心研究,随机对照试验
doi：
更新日期：2008-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：10.3851/IMP2688
更新日期：2013-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2007-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.3851/IMP2940
更新日期：2015-01-01 00:00:00
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pub_type： 杂志文章,评审
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journal_title：Antiviral therapy
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2004-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：2011-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 临床试验,杂志文章
doi：
更新日期：1996-04-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,meta分析
doi：
更新日期：2004-04-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,评审
doi：
更新日期：2008-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,多中心研究
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更新日期：2018-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,多中心研究,随机对照试验
doi：
更新日期：2006-01-01 00:00:00
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pub_type： 杂志文章,评审
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doi：
更新日期：2000-09-01 00:00:00
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journal_title：Antiviral therapy
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