Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings
Identifieur interne : 005714 ( Main/Exploration ); précédent : 005713; suivant : 005715Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings
Auteurs : C M Chu [Hong Kong] ; V C C. Cheng [Hong Kong] ; I F N. Hung [Hong Kong] ; M M L. Wong [Hong Kong] ; K H Chan [Hong Kong] ; K S Chan [Hong Kong] ; R Y T. Kao [Hong Kong] ; L L M. Poon [Hong Kong] ; C L P. Wong [Hong Kong] ; Y. Guan [Hong Kong] ; J S M. Peiris [Hong Kong] ; K Y Yuen [Hong Kong]Source :
- Thorax [ 0040-6376 ] ; 2004-03.
English descriptors
- KwdEn :
- Teeft :
- Adverse outcome, Adverse outcome rate, Antiviral, Antiviral activity, Antiviral agents, Antiviral susceptibility testing, Ards, Ards criteria, Baseline characteristics, Better outcome, Causal agent, Chan, Chequerboard assay, Christian hospital, Clinical features, Coronavirus, Cumulative pulse methylprednisolone dose, Cytopathic effect, Distress syndrome, Further analyses, High dose, Historical control group, Historical controls, Hong kong, Immunopathological damage, Inhibitory effect, Initial treatment, Initial treatment subgroup, Intensive care, Inverted curve, Lactate dehydrogenase, Lopinavir, Median time, Methylprednisolone, Microtitre plates, Milder disease course, Multivariate analysis, Nasopharyngeal swabs, Nosocomial infections, Novel coronavirus, Odds ratio, Open study, Previous study, Progressive decrease, Prospective study, Pulse methylprednisolone, Queen mary hospital, Reasonable balance, Replicative phase, Rescue treatment subgroup, Respir crit care, Respiratory syndrome, Ribavirin, Ritonavir, Ritonavir treatment, Same protocol, Sars, Sars coronavirus, Sars patients, Sars study group, Significant difference, Steroid, Stool positivity rate, Subgroup, Syndrome, Time periods, Treatment group, Viral, Viral load, Viral replication.
Abstract
Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.
Url:
- https://api.istex.fr/ark:/67375/NVC-RMJNBTWN-0/fulltext.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746980
DOI: 10.1136/thorax.2003.012658
Affiliations:
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<term>Antiviral activity</term>
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<term>Distress syndrome</term>
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<term>High dose</term>
<term>Historical control group</term>
<term>Historical controls</term>
<term>Hong kong</term>
<term>Immunopathological damage</term>
<term>Inhibitory effect</term>
<term>Initial treatment</term>
<term>Initial treatment subgroup</term>
<term>Intensive care</term>
<term>Inverted curve</term>
<term>Lactate dehydrogenase</term>
<term>Lopinavir</term>
<term>Median time</term>
<term>Methylprednisolone</term>
<term>Microtitre plates</term>
<term>Milder disease course</term>
<term>Multivariate analysis</term>
<term>Nasopharyngeal swabs</term>
<term>Nosocomial infections</term>
<term>Novel coronavirus</term>
<term>Odds ratio</term>
<term>Open study</term>
<term>Previous study</term>
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<term>Prospective study</term>
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<term>Replicative phase</term>
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<front><div type="abstract" xml:lang="en">Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.</div>
</front>
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