Safety of hydroxychloroquine and darunavir or lopinavir in COVID-19 infection.
Identifieur interne : 000791 ( Main/Corpus ); précédent : 000790; suivant : 000792Safety of hydroxychloroquine and darunavir or lopinavir in COVID-19 infection.
Auteurs : Etienne Meriglier ; Claire Rivoisy ; Mojgan Hessamfar ; Noelle Bernard ; Ines Aureau ; Joelle Lapoirie ; Anne Contis ; Frédéric Sacher ; Benjamin Sacristan ; Marin Lahouati ; Stéphane Pedeboscq ; Marie-Anne Vandenhende ; Stéphane Bouchet ; Fabrice BonnetSource :
- The Journal of antimicrobial chemotherapy [ 1460-2091 ] ; 2021.
English descriptors
- KwdEn :
- Antiviral Agents (administration & dosage), Antiviral Agents (adverse effects), Antiviral Agents (blood), Antiviral Agents (therapeutic use), COVID-19 (drug therapy), COVID-19 (epidemiology), Cohort Studies (MeSH), Darunavir (administration & dosage), Darunavir (adverse effects), Darunavir (blood), Darunavir (therapeutic use), Drug Therapy, Combination (MeSH), Electrocardiography (MeSH), France (MeSH), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (adverse effects), Hydroxychloroquine (blood), Hydroxychloroquine (therapeutic use), Long QT Syndrome (chemically induced), Long QT Syndrome (epidemiology), Lopinavir (administration & dosage), Lopinavir (adverse effects), Lopinavir (blood), Lopinavir (therapeutic use), SARS-CoV-2 (MeSH), Severity of Illness Index (MeSH), Treatment Outcome (MeSH).
- MESH :
- chemical , administration & dosage : Antiviral Agents, Darunavir, Hydroxychloroquine, Lopinavir.
- chemical , adverse effects : Antiviral Agents, Darunavir, Hydroxychloroquine, Lopinavir.
- chemical , blood : Antiviral Agents, Darunavir, Hydroxychloroquine, Lopinavir.
- chemical , therapeutic use : Antiviral Agents, Darunavir, Hydroxychloroquine, Lopinavir.
- geographic : France.
- chemically induced : Long QT Syndrome.
- drug therapy : COVID-19.
- epidemiology : COVID-19, Long QT Syndrome.
- Cohort Studies, Drug Therapy, Combination, Electrocardiography, Humans, SARS-CoV-2, Severity of Illness Index, Treatment Outcome.
Abstract
BACKGROUND
Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection.
OBJECTIVES
To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir.
METHODS
This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines.
RESULTS
Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration.
CONCLUSIONS
Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.
DOI: 10.1093/jac/dkaa441
PubMed: 33221868
PubMed Central: PMC7717306
Links to Exploration step
pubmed:33221868Le document en format XML
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<author><name sortKey="Meriglier, Etienne" sort="Meriglier, Etienne" uniqKey="Meriglier E" first="Etienne" last="Meriglier">Etienne Meriglier</name>
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</affiliation>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
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<author><name sortKey="Rivoisy, Claire" sort="Rivoisy, Claire" uniqKey="Rivoisy C" first="Claire" last="Rivoisy">Claire Rivoisy</name>
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<author><name sortKey="Lapoirie, Joelle" sort="Lapoirie, Joelle" uniqKey="Lapoirie J" first="Joelle" last="Lapoirie">Joelle Lapoirie</name>
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<author><name sortKey="Contis, Anne" sort="Contis, Anne" uniqKey="Contis A" first="Anne" last="Contis">Anne Contis</name>
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<author><name sortKey="Sacher, Frederic" sort="Sacher, Frederic" uniqKey="Sacher F" first="Frédéric" last="Sacher">Frédéric Sacher</name>
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<affiliation><nlm:affiliation>IHU LIRYC, Université de Bordeaux, CHU de Bordeaux, Service de cardiologie, Hôpital Haut-Lévêque, F-33000 Bordeaux, France.</nlm:affiliation>
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<author><name sortKey="Sacristan, Benjamin" sort="Sacristan, Benjamin" uniqKey="Sacristan B" first="Benjamin" last="Sacristan">Benjamin Sacristan</name>
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<author><name sortKey="Pedeboscq, Stephane" sort="Pedeboscq, Stephane" uniqKey="Pedeboscq S" first="Stéphane" last="Pedeboscq">Stéphane Pedeboscq</name>
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<author><name sortKey="Vandenhende, Marie Anne" sort="Vandenhende, Marie Anne" uniqKey="Vandenhende M" first="Marie-Anne" last="Vandenhende">Marie-Anne Vandenhende</name>
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</affiliation>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
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<author><name sortKey="Bouchet, Stephane" sort="Bouchet, Stephane" uniqKey="Bouchet S" first="Stéphane" last="Bouchet">Stéphane Bouchet</name>
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<author><name sortKey="Bonnet, Fabrice" sort="Bonnet, Fabrice" uniqKey="Bonnet F" first="Fabrice" last="Bonnet">Fabrice Bonnet</name>
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<author><name sortKey="Hessamfar, Mojgan" sort="Hessamfar, Mojgan" uniqKey="Hessamfar M" first="Mojgan" last="Hessamfar">Mojgan Hessamfar</name>
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<author><name sortKey="Lapoirie, Joelle" sort="Lapoirie, Joelle" uniqKey="Lapoirie J" first="Joelle" last="Lapoirie">Joelle Lapoirie</name>
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</affiliation>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Contis, Anne" sort="Contis, Anne" uniqKey="Contis A" first="Anne" last="Contis">Anne Contis</name>
<affiliation><nlm:affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sacher, Frederic" sort="Sacher, Frederic" uniqKey="Sacher F" first="Frédéric" last="Sacher">Frédéric Sacher</name>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>IHU LIRYC, Université de Bordeaux, CHU de Bordeaux, Service de cardiologie, Hôpital Haut-Lévêque, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sacristan, Benjamin" sort="Sacristan, Benjamin" uniqKey="Sacristan B" first="Benjamin" last="Sacristan">Benjamin Sacristan</name>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lahouati, Marin" sort="Lahouati, Marin" uniqKey="Lahouati M" first="Marin" last="Lahouati">Marin Lahouati</name>
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</affiliation>
</author>
<author><name sortKey="Pedeboscq, Stephane" sort="Pedeboscq, Stephane" uniqKey="Pedeboscq S" first="Stéphane" last="Pedeboscq">Stéphane Pedeboscq</name>
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</affiliation>
</author>
<author><name sortKey="Vandenhende, Marie Anne" sort="Vandenhende, Marie Anne" uniqKey="Vandenhende M" first="Marie-Anne" last="Vandenhende">Marie-Anne Vandenhende</name>
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</affiliation>
<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Bouchet, Stephane" sort="Bouchet, Stephane" uniqKey="Bouchet S" first="Stéphane" last="Bouchet">Stéphane Bouchet</name>
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</affiliation>
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<author><name sortKey="Bonnet, Fabrice" sort="Bonnet, Fabrice" uniqKey="Bonnet F" first="Fabrice" last="Bonnet">Fabrice Bonnet</name>
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<affiliation><nlm:affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</nlm:affiliation>
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<series><title level="j">The Journal of antimicrobial chemotherapy</title>
<idno type="eISSN">1460-2091</idno>
<imprint><date when="2021" type="published">2021</date>
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<term>Antiviral Agents (adverse effects)</term>
<term>Antiviral Agents (blood)</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>COVID-19 (drug therapy)</term>
<term>COVID-19 (epidemiology)</term>
<term>Cohort Studies (MeSH)</term>
<term>Darunavir (administration & dosage)</term>
<term>Darunavir (adverse effects)</term>
<term>Darunavir (blood)</term>
<term>Darunavir (therapeutic use)</term>
<term>Drug Therapy, Combination (MeSH)</term>
<term>Electrocardiography (MeSH)</term>
<term>France (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (administration & dosage)</term>
<term>Hydroxychloroquine (adverse effects)</term>
<term>Hydroxychloroquine (blood)</term>
<term>Hydroxychloroquine (therapeutic use)</term>
<term>Long QT Syndrome (chemically induced)</term>
<term>Long QT Syndrome (epidemiology)</term>
<term>Lopinavir (administration & dosage)</term>
<term>Lopinavir (adverse effects)</term>
<term>Lopinavir (blood)</term>
<term>Lopinavir (therapeutic use)</term>
<term>SARS-CoV-2 (MeSH)</term>
<term>Severity of Illness Index (MeSH)</term>
<term>Treatment Outcome (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiviral Agents</term>
<term>Darunavir</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiviral Agents</term>
<term>Darunavir</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antiviral Agents</term>
<term>Darunavir</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term>
<term>Darunavir</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
</keywords>
<keywords scheme="MESH" type="geographic" xml:lang="en"><term>France</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Long QT Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term>
<term>Long QT Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cohort Studies</term>
<term>Drug Therapy, Combination</term>
<term>Electrocardiography</term>
<term>Humans</term>
<term>SARS-CoV-2</term>
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<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<p>Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>OBJECTIVES</b>
</p>
<p>To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b>
</p>
<p>Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33221868</PMID>
<DateCompleted><Year>2021</Year>
<Month>02</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised><Year>2021</Year>
<Month>02</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1460-2091</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>76</Volume>
<Issue>2</Issue>
<PubDate><Year>2021</Year>
<Month>01</Month>
<Day>19</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of antimicrobial chemotherapy</Title>
<ISOAbbreviation>J Antimicrob Chemother</ISOAbbreviation>
</Journal>
<ArticleTitle>Safety of hydroxychloroquine and darunavir or lopinavir in COVID-19 infection.</ArticleTitle>
<Pagination><MedlinePgn>482-486</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/jac/dkaa441</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection.</AbstractText>
<AbstractText Label="OBJECTIVES">To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir.</AbstractText>
<AbstractText Label="METHODS">This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines.</AbstractText>
<AbstractText Label="RESULTS">Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration.</AbstractText>
<AbstractText Label="CONCLUSIONS">Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.</AbstractText>
<CopyrightInformation>© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Meriglier</LastName>
<ForeName>Etienne</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rivoisy</LastName>
<ForeName>Claire</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hessamfar</LastName>
<ForeName>Mojgan</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bernard</LastName>
<ForeName>Noelle</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aureau</LastName>
<ForeName>Ines</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lapoirie</LastName>
<ForeName>Joelle</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Contis</LastName>
<ForeName>Anne</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sacher</LastName>
<ForeName>Frédéric</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>IHU LIRYC, Université de Bordeaux, CHU de Bordeaux, Service de cardiologie, Hôpital Haut-Lévêque, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sacristan</LastName>
<ForeName>Benjamin</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lahouati</LastName>
<ForeName>Marin</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de pharmacie clinique des médicaments, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pedeboscq</LastName>
<ForeName>Stéphane</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de pharmacie clinique des médicaments, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vandenhende</LastName>
<ForeName>Marie-Anne</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bouchet</LastName>
<ForeName>Stéphane</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Laboratoire de pharmacologie - toxicologie, Hôpital Pellegrin, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bonnet</LastName>
<ForeName>Fabrice</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>CHU de Bordeaux, Service de médecine interne et maladies infectieuses, Hôpital Saint-André, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Univ. Bordeaux, F-33000 Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D064888">Observational Study</PublicationType>
</PublicationTypeList>
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<MedlineJournalInfo><Country>England</Country>
<MedlineTA>J Antimicrob Chemother</MedlineTA>
<NlmUniqueID>7513617</NlmUniqueID>
<ISSNLinking>0305-7453</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>2494G1JF75</RegistryNumber>
<NameOfSubstance UI="D061466">Lopinavir</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>YO603Y8113</RegistryNumber>
<NameOfSubstance UI="D000069454">Darunavir</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000069454" MajorTopicYN="N">Darunavir</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004359" MajorTopicYN="N">Drug Therapy, Combination</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005602" MajorTopicYN="N" Type="Geographic">France</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008133" MajorTopicYN="N">Long QT Syndrome</DescriptorName>
<QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061466" MajorTopicYN="N">Lopinavir</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>06</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>09</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>11</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2021</Year>
<Month>2</Month>
<Day>3</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>11</Month>
<Day>22</Day>
<Hour>20</Hour>
<Minute>42</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">33221868</ArticleId>
<ArticleId IdType="pii">5998282</ArticleId>
<ArticleId IdType="doi">10.1093/jac/dkaa441</ArticleId>
<ArticleId IdType="pmc">PMC7717306</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
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