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Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.

ABSTRACT: The standard of care for HCV genotype 1 is a protease inhibitor (telaprevir or boceprevir) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV). A lead-in phase of PEG-IFN/RBV therapy before addition of the protease inhibitor has been used, with the aim of improving response rates by reducing the development of protease inhibitor resistance. However, whether such a strategy can bring benefit to patients is unclear.A viral dynamic model was used to compare in silico HCV dynamics in patients treated with a period of PEG-IFN/RBV lead-in therapy followed by the addition of a protease inhibitor versus immediate triple therapy without lead-in.The model predicts that both regimens result in a similar end-of-treatment viral load change (viral decline or breakthrough). Thus, the current lead-in strategy may not decrease the rate of viral breakthrough/relapse or increase the rate of sustained virological response. This agrees with available data from clinical trials of several HCV protease inhibitors, such as telaprevir, boceprevir and faldaprevir.These results suggest that current PEG-IFN/RBV lead-in strategies may not improve treatment outcomes. However, viral kinetics during a period of PEG-IFN/RBV therapy, combined with other factors, such as the IL28B polymorphism and baseline viral load, can identify IFN-sensitive patients and help develop response-guided therapies.

SUBMITTER: Rong L

PROVIDER: S-EPMC4101064 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.

Rong Libin L Guedj Jeremie J Dahari Harel H Perelson Alan S AS

Antiviral therapy 20140116 5

<h4>Background</h4>The standard of care for HCV genotype 1 is a protease inhibitor (telaprevir or boceprevir) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV). A lead-in phase of PEG-IFN/RBV therapy before addition of the protease inhibitor has been used, with the aim of improving response rates by reducing the development of protease inhibitor resistance. However, whether such a strategy can bring benefit to patients is unclear.<h4>Methods</h4>A viral dynamic model was used to c ...[more]

PMID: 24434478

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Project description:ObjectivesTo investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India.DesignMathematical modelling.SettingsIndian epidemic of COVID-19 and vulnerable population.Data sourcesCountry-specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain.ModelAn age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed.InterventionsComparison of different vaccine strategies by targeting priority groups such as keyworkers including healthcare professionals, individuals with comorbidities (24-60 years old) and all above 60.Main outcome measuresIncidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented.ResultsThe priority groups together account for about 18% of India's population. An infection-preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (UI) 16.7-25.4) and cumulative mortality by 29.7% (95% CrI 25.8-33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4-13.0) and cumulative mortality by 32.9% (95% CrI 28.6-37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are >60 and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely populated rural areas, those with comorbidities should be prioritised after keyworkers.ConclusionsAn appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogeneity. 'Smart vaccination', based on public health considerations, rather than mass vaccination, appears prudent.

Dataset Information

Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.

Publications

Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.

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