Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load.
Identifieur interne : 000358 ( Main/Exploration ); précédent : 000357; suivant : 000359Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load.
Auteurs : Antonio Gonçalves [France] ; Julie Bertrand [France] ; Ruian Ke [États-Unis] ; Emmanuelle Comets [France] ; Xavier De Lamballerie [France] ; Denis Malvy [France] ; Andrés Pizzorno [France] ; Olivier Terrier [France] ; Manuel Rosa Calatrava [France] ; France Mentré [France] ; Patrick Smith [États-Unis] ; Alan S. Perelson [États-Unis] ; Jérémie Guedj [France]Source :
- CPT: pharmacometrics & systems pharmacology [ 2163-8306 ] ; 2020.
Abstract
We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.
DOI: 10.1002/psp4.12543
PubMed: 32558354
PubMed Central: PMC7323384
Affiliations:
- France, États-Unis
- Aquitaine, Auvergne-Rhône-Alpes, New Jersey, Nouveau-Mexique, Nouvelle-Aquitaine, Provence-Alpes-Côte d'Azur, Rhône-Alpes, Île-de-France
- Bordeaux, Lyon, Marseille, Paris
- Université de Bordeaux
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Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa Calatrava">Manuel Rosa Calatrava</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Mentre, France" sort="Mentre, France" uniqKey="Mentre F" first="France" last="Mentré">France Mentré</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Smith, Patrick" sort="Smith, Patrick" uniqKey="Smith P" first="Patrick" last="Smith">Patrick Smith</name><affiliation wicri:level="2"><nlm:affiliation>Certara, Integrated Drug Development, Princeton, New Jersey, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Certara, Integrated Drug Development, Princeton, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Perelson, Alan S" sort="Perelson, Alan S" uniqKey="Perelson A" first="Alan S" last="Perelson">Alan S. 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wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bertrand, Julie" sort="Bertrand, Julie" uniqKey="Bertrand J" first="Julie" last="Bertrand">Julie Bertrand</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ke, Ruian" sort="Ke, Ruian" uniqKey="Ke R" first="Ruian" last="Ke">Ruian Ke</name><affiliation wicri:level="2"><nlm:affiliation>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico</wicri:regionArea><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Comets, Emmanuelle" sort="Comets, Emmanuelle" uniqKey="Comets E" first="Emmanuelle" last="Comets">Emmanuelle Comets</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name><affiliation wicri:level="3"><nlm:affiliation>Institut Hospitalo-Universitaire Méditerranée Infection, UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille University - IRD 190 - Inserm 1207 - EHESP), Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Hospitalo-Universitaire Méditerranée Infection, UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille University - IRD 190 - Inserm 1207 - EHESP), Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Malvy, Denis" sort="Malvy, Denis" uniqKey="Malvy D" first="Denis" last="Malvy">Denis Malvy</name><affiliation wicri:level="4"><nlm:affiliation>Inserm, UMR 1219, Université de Bordeaux, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 1219, Université de Bordeaux, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire de Bordeaux, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andrés" last="Pizzorno">Andrés Pizzorno</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa Calatrava">Manuel Rosa Calatrava</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Mentre, France" sort="Mentre, France" uniqKey="Mentre F" first="France" last="Mentré">France Mentré</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Smith, Patrick" sort="Smith, Patrick" uniqKey="Smith P" first="Patrick" last="Smith">Patrick Smith</name><affiliation wicri:level="2"><nlm:affiliation>Certara, Integrated Drug Development, Princeton, New Jersey, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Certara, Integrated Drug Development, Princeton, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Perelson, Alan S" sort="Perelson, Alan S" uniqKey="Perelson A" first="Alan S" last="Perelson">Alan S. Perelson</name><affiliation wicri:level="2"><nlm:affiliation>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico</wicri:regionArea><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Guedj, Jeremie" sort="Guedj, Jeremie" uniqKey="Guedj J" first="Jérémie" last="Guedj">Jérémie Guedj</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, INSERM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, INSERM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">CPT: pharmacometrics & systems pharmacology</title><idno type="eISSN">2163-8306</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32558354</PMID><DateRevised><Year>2020</Year><Month>08</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2163-8306</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Jun</Month><Day>18</Day></PubDate></JournalIssue><Title>CPT: pharmacometrics & systems pharmacology</Title><ISOAbbreviation>CPT Pharmacometrics Syst Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1002/psp4.12543</ELocationID><Abstract><AbstractText>We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.</AbstractText><CopyrightInformation>© 2020 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gonçalves</LastName><ForeName>Antonio</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Université de Paris, IAME, INSERM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bertrand</LastName><ForeName>Julie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Université de Paris, IAME, INSERM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ke</LastName><ForeName>Ruian</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Comets</LastName><ForeName>Emmanuelle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Université de Paris, IAME, INSERM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Lamballerie</LastName><ForeName>Xavier</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Institut Hospitalo-Universitaire Méditerranée Infection, UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille University - IRD 190 - Inserm 1207 - EHESP), Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malvy</LastName><ForeName>Denis</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Inserm, UMR 1219, Université de Bordeaux, Bordeaux, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pizzorno</LastName><ForeName>Andrés</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Terrier</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rosa Calatrava</LastName><ForeName>Manuel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mentré</LastName><ForeName>France</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université de Paris, IAME, INSERM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Certara, Integrated Drug Development, Princeton, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perelson</LastName><ForeName>Alan S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guedj</LastName><ForeName>Jérémie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Université de Paris, IAME, INSERM, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>89233218CNA000001</GrantID><Agency>Roche</Agency><Country></Country></Grant><Grant><GrantID>ANR-20-COVI-0018</GrantID><Agency>national Research Agency (ANR) through the ANR-Flash calls for COVID-19</Agency><Country></Country></Grant><Grant><Agency>US Department of Energy</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>06</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>CPT Pharmacometrics Syst Pharmacol</MedlineTA><NlmUniqueID>101580011</NlmUniqueID><ISSNLinking>2163-8306</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="UpdateOf"><RefSource>medRxiv. 2020 Apr 07;:</RefSource><PMID Version="1">32511641</PMID></CommentsCorrections></CommentsCorrectionsList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>05</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>06</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>6</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>6</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>6</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32558354</ArticleId><ArticleId IdType="doi">10.1002/psp4.12543</ArticleId><ArticleId IdType="pmc">PMC7323384</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Cao, B. et al. 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Perelson</name><name sortKey="Smith, Patrick" sort="Smith, Patrick" uniqKey="Smith P" first="Patrick" last="Smith">Patrick Smith</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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