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Article: Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings

TitleRole of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings
Authors
Issue Date2004
PublisherB M J Publishing Group. The Journal's web site is located at http://thorax.bmjjournals.com/
Citation
Thorax, 2004, v. 59 n. 3, p. 252-256 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/43139
ISSN
2015 Impact Factor: 8.121
2015 SCImago Journal Rankings: 3.650
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChu, CMen_HK
dc.contributor.authorCheng, VCCen_HK
dc.contributor.authorHung, IFNen_HK
dc.contributor.authorWong, MMLen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorChan, KSen_HK
dc.contributor.authorKao, RYTen_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorWong, CLPen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2007-03-23T04:39:45Z-
dc.date.available2007-03-23T04:39:45Z-
dc.date.issued2004en_HK
dc.identifier.citationThorax, 2004, v. 59 n. 3, p. 252-256en_HK
dc.identifier.issn0040-6376en_HK
dc.identifier.urihttp://hdl.handle.net/10722/43139-
dc.description.abstractBackground: 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.en_HK
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dc.languageengen_HK
dc.publisherB M J Publishing Group. The Journal's web site is located at http://thorax.bmjjournals.com/en_HK
dc.relation.ispartofThoraxen_HK
dc.rightsThorax. Copyright © B M J Publishing Group.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshSevere acute respiratory syndrome - drug therapy - virologyen_HK
dc.subject.meshHiv protease inhibitors - therapeutic useen_HK
dc.subject.meshPyrimidinones - therapeutic useen_HK
dc.subject.meshRitonavir - therapeutic useen_HK
dc.subject.meshCross infection - complicationsen_HK
dc.titleRole of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findingsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0040-6376&volume=59&issue=3&spage=252&epage=256&date=2004&atitle=Role+of+lopinavir/ritonavir+in+the+treatment+of+SARS:+initial+virological+and+clinical+findingsen_HK
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hken_HK
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hken_HK
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityHung, IFN=rp00508en_HK
dc.identifier.authorityKao, RYT=rp00481en_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/thorax.2003.012658en_HK
dc.identifier.pmid14985565en_HK
dc.identifier.pmcidPMC1746980-
dc.identifier.scopuseid_2-s2.0-12144290587en_HK
dc.identifier.hkuros87739-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-12144290587&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue3en_HK
dc.identifier.spage252en_HK
dc.identifier.epage256en_HK
dc.identifier.isiWOS:000189217200016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChu, CM=7404345558en_HK
dc.identifier.scopusauthoridCheng, VCC=23670479400en_HK
dc.identifier.scopusauthoridHung, IFN=7006103457en_HK
dc.identifier.scopusauthoridWong, MML=9278575000en_HK
dc.identifier.scopusauthoridChan, KH=35338760600en_HK
dc.identifier.scopusauthoridChan, KS=7406031627en_HK
dc.identifier.scopusauthoridKao, RYT=7101675499en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridWong, CLP=16505759800en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK

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