Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial
Identifieur interne : 000657 ( Istex/Corpus ); précédent : 000656; suivant : 000658Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial
Auteurs : Anne M. M. Been-Tiktak ; Charles A. B. Boucher ; Françoise Brun-Vezinet ; Véronique Joly ; Jan W. Mulder ; J. Jost ; David A. Cooper ; Mauro Moroni ; José M. Gatell ; Schlomo Staszewski ; Robert Colebunders ; Graeme J. Stewart ; David A. Hawkins ; Margaret A. Johnson ; Jacqueline M. Parkin ; Dermot H. Kennedy ; Jennifer F. Hoy ; Jan C. C. BorleffsSource :
- International Journal of Antimicrobial Agents [ 0924-8579 ] ; 1999.
English descriptors
- KwdEn :
- Antimicrob, Antimicrob agents chemother, Antimicrobial, Antimicrobial agents, Antiretroviral, Antiviral, Antiviral effect, Baseline, Cell count, Cell counts, Chemother, Clinical endpoints, Combination therapy, Delavirdine, Dose group, HIV, Human virus type, Infectious diseases, Inhibitor, Internal medicine, International journal, Median, Monotherapy, Nnrti, Nonnucleoside, Placebo, Proc natl acad, Rash, Regimen, Skin rash, Susceptibility, Transcriptase, Transcriptase inhibitor, Transcriptase inhibitors, Treatment groups, Viral, Viral susceptibility, Virus type, Zidovudine, Zidovudine monotherapy.
- Teeft :
- Antimicrob, Antimicrob agents chemother, Antimicrobial, Antimicrobial agents, Antiretroviral, Antiviral, Antiviral effect, Baseline, Cell count, Cell counts, Chemother, Clinical endpoints, Combination therapy, Delavirdine, Dose group, Human virus type, Infectious diseases, Inhibitor, Internal medicine, International journal, Median, Monotherapy, Nnrti, Nonnucleoside, Placebo, Proc natl acad, Rash, Regimen, Skin rash, Susceptibility, Transcriptase, Transcriptase inhibitor, Transcriptase inhibitors, Treatment groups, Viral, Viral susceptibility, Virus type, Zidovudine, Zidovudine monotherapy.
Abstract
Abstract: The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4+ cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.
Url:
DOI: 10.1016/S0924-8579(98)00082-X
Links to Exploration step
ISTEX:222583409E60A1F786D16E3885AE2D79E27D7FAELe document en format XML
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Borleffs</name><affiliation><mods:affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. 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Been-Tiktak</name><affiliation><mods:affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Boucher, Charles A B" sort="Boucher, Charles A B" uniqKey="Boucher C" first="Charles A. B." last="Boucher">Charles A. B. Boucher</name><affiliation><mods:affiliation>Eijkman–Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Brun Vezinet, Francoise" sort="Brun Vezinet, Francoise" uniqKey="Brun Vezinet F" first="Françoise" last="Brun-Vezinet">Françoise Brun-Vezinet</name><affiliation><mods:affiliation>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Joly, Veronique" sort="Joly, Veronique" uniqKey="Joly V" first="Véronique" last="Joly">Véronique Joly</name><affiliation><mods:affiliation>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mulder, Jan W" sort="Mulder, Jan W" uniqKey="Mulder J" first="Jan W." last="Mulder">Jan W. Mulder</name><affiliation><mods:affiliation>Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Jost, J" sort="Jost, J" uniqKey="Jost J" first="J." last="Jost">J. Jost</name><affiliation><mods:affiliation>Department of Infectious Diseases, University Hospital, Zürich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><affiliation><mods:affiliation>HIV Medicine Unit, St Vincent’s Hospital, Sydney, Australia</mods:affiliation></affiliation></author><author><name sortKey="Moroni, Mauro" sort="Moroni, Mauro" uniqKey="Moroni M" first="Mauro" last="Moroni">Mauro Moroni</name><affiliation><mods:affiliation>Clinic of Infectious Diseases, Sant’ Orsola Hospital, Bologna, Italy</mods:affiliation></affiliation></author><author><name sortKey="Gatell, Jose M" sort="Gatell, Jose M" uniqKey="Gatell J" first="José M." last="Gatell">José M. Gatell</name><affiliation><mods:affiliation>Servicio de Infecciones, Hospital Clinic i Provincial, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Staszewski, Schlomo" sort="Staszewski, Schlomo" uniqKey="Staszewski S" first="Schlomo" last="Staszewski">Schlomo Staszewski</name><affiliation><mods:affiliation>Department of Infectious Diseases, Goethe University Hospital, Frankfurt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Colebunders, Robert" sort="Colebunders, Robert" uniqKey="Colebunders R" first="Robert" last="Colebunders">Robert Colebunders</name><affiliation><mods:affiliation>Institute of Tropical Medicine, Antwerp, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Stewart, Graeme J" sort="Stewart, Graeme J" uniqKey="Stewart G" first="Graeme J." last="Stewart">Graeme J. Stewart</name><affiliation><mods:affiliation>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</mods:affiliation></affiliation></author><author><name sortKey="Hawkins, David A" sort="Hawkins, David A" uniqKey="Hawkins D" first="David A." last="Hawkins">David A. Hawkins</name><affiliation><mods:affiliation>St. Stephen’s Centre, Chelsea and Westminster Hospital, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Johnson, Margaret A" sort="Johnson, Margaret A" uniqKey="Johnson M" first="Margaret A." last="Johnson">Margaret A. Johnson</name><affiliation><mods:affiliation>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Parkin, Jacqueline M" sort="Parkin, Jacqueline M" uniqKey="Parkin J" first="Jacqueline M." last="Parkin">Jacqueline M. Parkin</name><affiliation><mods:affiliation>Department of Immunology, St. Bartholomews Hospital, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Kennedy, Dermot H" sort="Kennedy, Dermot H" uniqKey="Kennedy D" first="Dermot H." last="Kennedy">Dermot H. Kennedy</name><affiliation><mods:affiliation>Department of Infection and Tropical Medicine, Ruchill Hospital, Glasgow, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Hoy, Jennifer F" sort="Hoy, Jennifer F" uniqKey="Hoy J" first="Jennifer F." last="Hoy">Jennifer F. Hoy</name><affiliation><mods:affiliation>Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia</mods:affiliation></affiliation></author><author><name sortKey="Borleffs, Jan C C" sort="Borleffs, Jan C C" uniqKey="Borleffs J" first="Jan C. C." last="Borleffs">Jan C. C. Borleffs</name><affiliation><mods:affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">International Journal of Antimicrobial Agents</title><title level="j" type="abbrev">ANTAGE</title><idno type="ISSN">0924-8579</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">11</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="13">13</biblScope><biblScope unit="page" to="21">21</biblScope></imprint><idno type="ISSN">0924-8579</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0924-8579</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antimicrob</term><term>Antimicrob agents chemother</term><term>Antimicrobial</term><term>Antimicrobial agents</term><term>Antiretroviral</term><term>Antiviral</term><term>Antiviral effect</term><term>Baseline</term><term>Cell count</term><term>Cell counts</term><term>Chemother</term><term>Clinical endpoints</term><term>Combination therapy</term><term>Delavirdine</term><term>Dose group</term><term>HIV</term><term>Human virus type</term><term>Infectious diseases</term><term>Inhibitor</term><term>Internal medicine</term><term>International journal</term><term>Median</term><term>Monotherapy</term><term>Nnrti</term><term>Nonnucleoside</term><term>Placebo</term><term>Proc natl acad</term><term>Rash</term><term>Regimen</term><term>Skin rash</term><term>Susceptibility</term><term>Transcriptase</term><term>Transcriptase inhibitor</term><term>Transcriptase inhibitors</term><term>Treatment groups</term><term>Viral</term><term>Viral susceptibility</term><term>Virus type</term><term>Zidovudine</term><term>Zidovudine monotherapy</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Antimicrob</term><term>Antimicrob agents chemother</term><term>Antimicrobial</term><term>Antimicrobial agents</term><term>Antiretroviral</term><term>Antiviral</term><term>Antiviral effect</term><term>Baseline</term><term>Cell count</term><term>Cell counts</term><term>Chemother</term><term>Clinical endpoints</term><term>Combination therapy</term><term>Delavirdine</term><term>Dose group</term><term>Human virus type</term><term>Infectious diseases</term><term>Inhibitor</term><term>Internal medicine</term><term>International journal</term><term>Median</term><term>Monotherapy</term><term>Nnrti</term><term>Nonnucleoside</term><term>Placebo</term><term>Proc natl acad</term><term>Rash</term><term>Regimen</term><term>Skin rash</term><term>Susceptibility</term><term>Transcriptase</term><term>Transcriptase inhibitor</term><term>Transcriptase inhibitors</term><term>Treatment groups</term><term>Viral</term><term>Viral susceptibility</term><term>Virus type</term><term>Zidovudine</term><term>Zidovudine monotherapy</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4+ cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>delavirdine</json:string><json:string>zidovudine</json:string><json:string>placebo</json:string><json:string>transcriptase</json:string><json:string>skin rash</json:string><json:string>nnrti</json:string><json:string>human virus type</json:string><json:string>combination therapy</json:string><json:string>antiviral</json:string><json:string>baseline</json:string><json:string>rash</json:string><json:string>antimicrob agents chemother</json:string><json:string>dose group</json:string><json:string>chemother</json:string><json:string>monotherapy</json:string><json:string>antimicrobial agents</json:string><json:string>antiretroviral</json:string><json:string>antimicrob</json:string><json:string>international journal</json:string><json:string>antimicrobial</json:string><json:string>treatment groups</json:string><json:string>cell count</json:string><json:string>viral</json:string><json:string>nonnucleoside</json:string><json:string>transcriptase inhibitors</json:string><json:string>infectious diseases</json:string><json:string>antiviral effect</json:string><json:string>transcriptase inhibitor</json:string><json:string>median</json:string><json:string>inhibitor</json:string><json:string>cell counts</json:string><json:string>proc natl acad</json:string><json:string>susceptibility</json:string><json:string>regimen</json:string><json:string>zidovudine monotherapy</json:string><json:string>internal medicine</json:string><json:string>viral susceptibility</json:string><json:string>virus type</json:string><json:string>clinical endpoints</json:string></teeft></keywords><author><json:item><name>Anne M.M. Been-Tiktak</name><affiliations><json:string>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</json:string></affiliations></json:item><json:item><name>Charles A.B. Boucher</name><affiliations><json:string>Eijkman–Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands</json:string></affiliations></json:item><json:item><name>Françoise Brun-Vezinet</name><affiliations><json:string>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Véronique Joly</name><affiliations><json:string>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Jan W. Mulder</name><affiliations><json:string>Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands</json:string></affiliations></json:item><json:item><name>J. Jost</name><affiliations><json:string>Department of Infectious Diseases, University Hospital, Zürich, Switzerland</json:string></affiliations></json:item><json:item><name>David A. Cooper</name><affiliations><json:string>HIV Medicine Unit, St Vincent’s Hospital, Sydney, Australia</json:string></affiliations></json:item><json:item><name>Mauro Moroni</name><affiliations><json:string>Clinic of Infectious Diseases, Sant’ Orsola Hospital, Bologna, Italy</json:string></affiliations></json:item><json:item><name>José M. Gatell</name><affiliations><json:string>Servicio de Infecciones, Hospital Clinic i Provincial, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Schlomo Staszewski</name><affiliations><json:string>Department of Infectious Diseases, Goethe University Hospital, Frankfurt, Germany</json:string></affiliations></json:item><json:item><name>Robert Colebunders</name><affiliations><json:string>Institute of Tropical Medicine, Antwerp, Belgium</json:string></affiliations></json:item><json:item><name>Graeme J. Stewart</name><affiliations><json:string>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</json:string></affiliations></json:item><json:item><name>David A. Hawkins</name><affiliations><json:string>St. Stephen’s Centre, Chelsea and Westminster Hospital, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Margaret A. Johnson</name><affiliations><json:string>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Jacqueline M. Parkin</name><affiliations><json:string>Department of Immunology, St. Bartholomews Hospital, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Dermot H. Kennedy</name><affiliations><json:string>Department of Infection and Tropical Medicine, Ruchill Hospital, Glasgow, United Kingdom</json:string></affiliations></json:item><json:item><name>Jennifer F. Hoy</name><affiliations><json:string>Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia</json:string></affiliations></json:item><json:item><name>Jan C.C. Borleffs</name><affiliations><json:string>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Delavirdine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HIV</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Zidovudine</value></json:item></subject><arkIstex>ark:/67375/6H6-JXZKHWVT-1</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4+ cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.</abstract><qualityIndicators><refBibsNative>true</refBibsNative><abstractWordCount>214</abstractWordCount><abstractCharCount>1481</abstractCharCount><keywordCount>3</keywordCount><score>9.392</score><pdfWordCount>4824</pdfWordCount><pdfCharCount>31423</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>552 x 768 pts</pdfPageSize></qualityIndicators><title>Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</title><pmid><json:string>10075273</json:string></pmid><pii><json:string>S0924-8579(98)00082-X</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>International Journal of Antimicrobial Agents</title><language><json:string>unknown</json:string></language><publicationDate>1999</publicationDate><issn><json:string>0924-8579</json:string></issn><pii><json:string>S0924-8579(00)X0026-X</json:string></pii><volume>11</volume><issue>1</issue><pages><first>13</first><last>21</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1999</json:string><json:string>Between October 1993 and July 1994</json:string></date><geogName></geogName><orgName><json:string>St Vincent’s Hospital, Sydney, Australia</json:string><json:string>Department of Internal Medicine, Sloter</json:string><json:string>Bartholomews Hospital, London, United Kingdom</json:string><json:string>Bichat-Claude Bernard Hospital, Paris, France</json:string><json:string>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</json:string><json:string>Orsola Hospital, Bologna, Italy</json:string><json:string>Clinical Research, Uni</json:string><json:string>Hospital Utrect</json:string><json:string>Department of Immunology, St</json:string><json:string>Ruchill Hospital, Glasgow, United Kingdom</json:string><json:string>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</json:string><json:string>Westminster Hospital, London, United Kingdom</json:string><json:string>Hospital, Zurich, Switzerland</json:string><json:string>Department of Microbiology and Infectious Diseases</json:string><json:string>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</json:string><json:string>Department of Infectious Diseases, Uni</json:string><json:string>Institute of Tropical Medicine, Antwerp, Belgium</json:string><json:string>Hospital, Frankfurt, Germany</json:string><json:string>Alfred Hospital, Melbourne, Australia</json:string><json:string>University Hospital, Utrecht, the Netherlands</json:string><json:string>Hospital Clinic</json:string><json:string>Department of Infection and Tropical Medicine</json:string><json:string>Australia Received</json:string><json:string>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</json:string><json:string>Eijkman–Winkler Institute of Medical Microbiology, Uni</json:string><json:string>Department of Defense</json:string><json:string>Department of Infectious Diseases, Goethe Uni</json:string><json:string>National Centre</json:string><json:string>Hospital, Utrecht, The Netherlands</json:string><json:string>Hospital, Amsterdam, The Netherlands</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Individuals</json:string><json:string>P.O. Box</json:string><json:string>J. Stewart</json:string><json:string>Veronique Joly</json:string><json:string>Preliminary</json:string><json:string>David A. Hawkins</json:string><json:string>Michael Rawlinson</json:string></persName><placeName><json:string>Utrecht</json:string><json:string>Australia</json:string><json:string>Helsinki</json:string><json:string>Europe</json:string><json:string>Wales</json:string><json:string>Barcelona</json:string><json:string>Amsterdam</json:string><json:string>Spain</json:string><json:string>St. Stephen</json:string><json:string>Belgium</json:string><json:string>Netherlands</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[12]</json:string><json:string>[37,38]</json:string><json:string>[29]</json:string><json:string>[6]</json:string><json:string>[33]</json:string><json:string>[31,32]</json:string><json:string>A.M.M. Been-Tiktak et al.</json:string><json:string>[39]</json:string><json:string>[34,35]</json:string><json:string>[30]</json:string><json:string>[36]</json:string><json:string>[1,2]</json:string><json:string>[13]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-JXZKHWVT-1</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - pharmacology & pharmacy</json:string><json:string>2 - microbiology</json:string><json:string>2 - infectious diseases</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - microbiology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Pharmacology (medical)</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Microbiology (medical)</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - General Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - pharmacologie. traitements medicamenteux</json:string></inist></categories><publicationDate>1999</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0924-8579(98)00082-X</json:string></doi><id>222583409E60A1F786D16E3885AE2D79E27D7FAE</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/222583409E60A1F786D16E3885AE2D79E27D7FAE/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/222583409E60A1F786D16E3885AE2D79E27D7FAE/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/222583409E60A1F786D16E3885AE2D79E27D7FAE/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©1999 Elsevier Science B.V.</p></availability><date>1999</date></publicationStmt><notesStmt><note type="content">Section title: Original article</note><note type="content">Fig. 1: Median changes from baseline of CD4 cell count per dose group. Baseline CD4 cell count is defined as the CD4 cell count of week 0 only. Patients receiving placebo during the first 12 weeks of the study were switched to delavirdine 900 mg/day at week 12. All patients received zidovudine or zidovudine/zalcitabine (zidovudine 600 mg/day, zalcitabine 2.25 mg/day) in combination with one of the dosages of delavirdine or placebo.</note><note type="content">Fig. 2: Median changes from baseline of HIV-1 RNA load. Baseline viral load was defined as log number of RNA copies of week 0 only. Patients receiving placebo during the first 12 weeks of the study were switched to delavirdine 900 mg/day at week 12. All patients received zidovudine or zidovudine/zalcitabine (zidovudine 600 mg/day, zalcitabine 2.25 mg/day) in combination with one of the dosages of delavirdine or placebo.</note><note type="content">Table 1: Entry characteristics of the treatment groups</note><note type="content">Table 2: Median susceptibility (IC50) of the clinical isolates for delavirdine and zidovudine at baseline (i.e., zidovudine monotherapy) and after 12 weeks of the combination therapy with zidovudine and delavirdine (600 mg, 1200 mg, escalating dose from 150 to 1200 mg) or continuation of zidovudine monotherapy (delavirdine placebo)</note><note type="content">Table 3: Incidence of adverse eventsa, clinical endpoints and dropouts</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</title><author xml:id="author-0000"><persName><forename type="first">Anne M.M.</forename><surname>Been-Tiktak</surname></persName><affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Charles A.B.</forename><surname>Boucher</surname></persName><affiliation>Eijkman–Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Françoise</forename><surname>Brun-Vezinet</surname></persName><affiliation>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Véronique</forename><surname>Joly</surname></persName><affiliation>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Jan W.</forename><surname>Mulder</surname></persName><affiliation>Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands</affiliation></author><author xml:id="author-0005"><persName><forename type="first">J.</forename><surname>Jost</surname></persName><affiliation>Department of Infectious Diseases, University Hospital, Zürich, Switzerland</affiliation></author><author xml:id="author-0006"><persName><forename type="first">David A.</forename><surname>Cooper</surname></persName><affiliation>HIV Medicine Unit, St Vincent’s Hospital, Sydney, Australia</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Mauro</forename><surname>Moroni</surname></persName><affiliation>Clinic of Infectious Diseases, Sant’ Orsola Hospital, Bologna, Italy</affiliation></author><author xml:id="author-0008"><persName><forename type="first">José M.</forename><surname>Gatell</surname></persName><affiliation>Servicio de Infecciones, Hospital Clinic i Provincial, Barcelona, Spain</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Schlomo</forename><surname>Staszewski</surname></persName><affiliation>Department of Infectious Diseases, Goethe University Hospital, Frankfurt, Germany</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Robert</forename><surname>Colebunders</surname></persName><affiliation>Institute of Tropical Medicine, Antwerp, Belgium</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Graeme J.</forename><surname>Stewart</surname></persName><affiliation>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</affiliation></author><author xml:id="author-0012"><persName><forename type="first">David A.</forename><surname>Hawkins</surname></persName><affiliation>St. Stephen’s Centre, Chelsea and Westminster Hospital, London, United Kingdom</affiliation></author><author xml:id="author-0013"><persName><forename type="first">Margaret A.</forename><surname>Johnson</surname></persName><affiliation>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</affiliation></author><author xml:id="author-0014"><persName><forename type="first">Jacqueline M.</forename><surname>Parkin</surname></persName><affiliation>Department of Immunology, St. Bartholomews Hospital, London, United Kingdom</affiliation></author><author xml:id="author-0015"><persName><forename type="first">Dermot H.</forename><surname>Kennedy</surname></persName><affiliation>Department of Infection and Tropical Medicine, Ruchill Hospital, Glasgow, United Kingdom</affiliation></author><author xml:id="author-0016"><persName><forename type="first">Jennifer F.</forename><surname>Hoy</surname></persName><affiliation>Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia</affiliation></author><author xml:id="author-0017"><persName><forename type="first">Jan C.C.</forename><surname>Borleffs</surname></persName><note type="correspondence"><p>Corresponding author. Tel.: +31-30-2513828; fax: +31-30-2513828</p></note><affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</affiliation></author><idno type="istex">222583409E60A1F786D16E3885AE2D79E27D7FAE</idno><idno type="DOI">10.1016/S0924-8579(98)00082-X</idno><idno type="PII">S0924-8579(98)00082-X</idno></analytic><monogr><title level="j">International Journal of Antimicrobial Agents</title><title level="j" type="abbrev">ANTAGE</title><idno type="pISSN">0924-8579</idno><idno type="PII">S0924-8579(00)X0026-X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999"></date><biblScope unit="volume">11</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="13">13</biblScope><biblScope unit="page" to="21">21</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4+ cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Delavirdine</term></item><item><term>HIV</term></item><item><term>Zidovudine</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/222583409E60A1F786D16E3885AE2D79E27D7FAE/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>ANTAGE</jid><aid>503</aid><ce:pii>S0924-8579(98)00082-X</ce:pii><ce:doi>10.1016/S0924-8579(98)00082-X</ce:doi><ce:copyright type="full-transfer" year="1999">Elsevier Science B.V.</ce:copyright></item-info><head><ce:dochead><ce:textfn>Original article</ce:textfn></ce:dochead><ce:title>Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</ce:title><ce:author-group><ce:author><ce:given-name>Anne M.M.</ce:given-name><ce:surname>Been-Tiktak</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Charles A.B.</ce:given-name><ce:surname>Boucher</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Françoise</ce:given-name><ce:surname>Brun-Vezinet</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Véronique</ce:given-name><ce:surname>Joly</ce:surname><ce:cross-ref refid="AFF4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jan W.</ce:given-name><ce:surname>Mulder</ce:surname><ce:cross-ref refid="AFF5"><ce:sup>e</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>J.</ce:given-name><ce:surname>Jost</ce:surname><ce:cross-ref refid="AFF6"><ce:sup>f</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>David A.</ce:given-name><ce:surname>Cooper</ce:surname><ce:cross-ref refid="AFF7"><ce:sup>g</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF18"><ce:sup>r</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Mauro</ce:given-name><ce:surname>Moroni</ce:surname><ce:cross-ref refid="AFF8"><ce:sup>h</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>José M.</ce:given-name><ce:surname>Gatell</ce:surname><ce:cross-ref refid="AFF9"><ce:sup>i</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Schlomo</ce:given-name><ce:surname>Staszewski</ce:surname><ce:cross-ref refid="AFF10"><ce:sup>j</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Robert</ce:given-name><ce:surname>Colebunders</ce:surname><ce:cross-ref refid="AFF11"><ce:sup>k</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Graeme J.</ce:given-name><ce:surname>Stewart</ce:surname><ce:cross-ref refid="AFF12"><ce:sup>l</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF18"><ce:sup>r</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>David A.</ce:given-name><ce:surname>Hawkins</ce:surname><ce:cross-ref refid="AFF13"><ce:sup>m</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Margaret A.</ce:given-name><ce:surname>Johnson</ce:surname><ce:cross-ref refid="AFF14"><ce:sup>n</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jacqueline M.</ce:given-name><ce:surname>Parkin</ce:surname><ce:cross-ref refid="AFF15"><ce:sup>o</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Dermot H.</ce:given-name><ce:surname>Kennedy</ce:surname><ce:cross-ref refid="AFF16"><ce:sup>p</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jennifer F.</ce:given-name><ce:surname>Hoy</ce:surname><ce:cross-ref refid="AFF17"><ce:sup>q</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF18"><ce:sup>r</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jan C.C.</ce:given-name><ce:surname>Borleffs</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Eijkman–Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</ce:textfn></ce:affiliation><ce:affiliation id="AFF4"><ce:label>d</ce:label><ce:textfn>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</ce:textfn></ce:affiliation><ce:affiliation id="AFF5"><ce:label>e</ce:label><ce:textfn>Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands</ce:textfn></ce:affiliation><ce:affiliation id="AFF6"><ce:label>f</ce:label><ce:textfn>Department of Infectious Diseases, University Hospital, Zürich, Switzerland</ce:textfn></ce:affiliation><ce:affiliation id="AFF7"><ce:label>g</ce:label><ce:textfn>HIV Medicine Unit, St Vincent’s Hospital, Sydney, Australia</ce:textfn></ce:affiliation><ce:affiliation id="AFF8"><ce:label>h</ce:label><ce:textfn>Clinic of Infectious Diseases, Sant’ Orsola Hospital, Bologna, Italy</ce:textfn></ce:affiliation><ce:affiliation id="AFF9"><ce:label>i</ce:label><ce:textfn>Servicio de Infecciones, Hospital Clinic i Provincial, Barcelona, Spain</ce:textfn></ce:affiliation><ce:affiliation id="AFF10"><ce:label>j</ce:label><ce:textfn>Department of Infectious Diseases, Goethe University Hospital, Frankfurt, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF11"><ce:label>k</ce:label><ce:textfn>Institute of Tropical Medicine, Antwerp, Belgium</ce:textfn></ce:affiliation><ce:affiliation id="AFF12"><ce:label>l</ce:label><ce:textfn>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</ce:textfn></ce:affiliation><ce:affiliation id="AFF13"><ce:label>m</ce:label><ce:textfn>St. Stephen’s Centre, Chelsea and Westminster Hospital, London, United Kingdom</ce:textfn></ce:affiliation><ce:affiliation id="AFF14"><ce:label>n</ce:label><ce:textfn>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</ce:textfn></ce:affiliation><ce:affiliation id="AFF15"><ce:label>o</ce:label><ce:textfn>Department of Immunology, St. Bartholomews Hospital, London, United Kingdom</ce:textfn></ce:affiliation><ce:affiliation id="AFF16"><ce:label>p</ce:label><ce:textfn>Department of Infection and Tropical Medicine, Ruchill Hospital, Glasgow, United Kingdom</ce:textfn></ce:affiliation><ce:affiliation id="AFF17"><ce:label>q</ce:label><ce:textfn>Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia</ce:textfn></ce:affiliation><ce:affiliation id="AFF18"><ce:label>r</ce:label><ce:textfn>National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +31-30-2513828; fax: +31-30-2513828</ce:text></ce:correspondence></ce:author-group><ce:date-received day="18" month="6" year="1998"></ce:date-received><ce:date-accepted day="2" month="10" year="1998"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4<ce:sup>+</ce:sup> cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4<ce:sup>+</ce:sup> cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Delavirdine</ce:text></ce:keyword><ce:keyword><ce:text>HIV</ce:text></ce:keyword><ce:keyword><ce:text>Zidovudine</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial</title></titleInfo><name type="personal"><namePart type="given">Anne M.M.</namePart><namePart type="family">Been-Tiktak</namePart><affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Charles A.B.</namePart><namePart type="family">Boucher</namePart><affiliation>Eijkman–Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Françoise</namePart><namePart type="family">Brun-Vezinet</namePart><affiliation>Department of Virology, Bichat-Claude Bernard Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Véronique</namePart><namePart type="family">Joly</namePart><affiliation>Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan W.</namePart><namePart type="family">Mulder</namePart><affiliation>Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">Jost</namePart><affiliation>Department of Infectious Diseases, University Hospital, Zürich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David A.</namePart><namePart type="family">Cooper</namePart><affiliation>HIV Medicine Unit, St Vincent’s Hospital, Sydney, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mauro</namePart><namePart type="family">Moroni</namePart><affiliation>Clinic of Infectious Diseases, Sant’ Orsola Hospital, Bologna, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">José M.</namePart><namePart type="family">Gatell</namePart><affiliation>Servicio de Infecciones, Hospital Clinic i Provincial, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Schlomo</namePart><namePart type="family">Staszewski</namePart><affiliation>Department of Infectious Diseases, Goethe University Hospital, Frankfurt, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert</namePart><namePart type="family">Colebunders</namePart><affiliation>Institute of Tropical Medicine, Antwerp, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Graeme J.</namePart><namePart type="family">Stewart</namePart><affiliation>Department of Clinical Immunology, Westmead Hospital, Sydney, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David A.</namePart><namePart type="family">Hawkins</namePart><affiliation>St. Stephen’s Centre, Chelsea and Westminster Hospital, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Margaret A.</namePart><namePart type="family">Johnson</namePart><affiliation>Department of Thoracic Surgery, Royal Free Hospital, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jacqueline M.</namePart><namePart type="family">Parkin</namePart><affiliation>Department of Immunology, St. Bartholomews Hospital, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dermot H.</namePart><namePart type="family">Kennedy</namePart><affiliation>Department of Infection and Tropical Medicine, Ruchill Hospital, Glasgow, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jennifer F.</namePart><namePart type="family">Hoy</namePart><affiliation>Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan C.C.</namePart><namePart type="family">Borleffs</namePart><affiliation>Department of Internal Medicine, Subdivision of Infectious Diseases and AIDS, University Hospital Utrect, P.O. Box 85500, 3508 GA Utrecht, The Netherlands</affiliation><description>Corresponding author. Tel.: +31-30-2513828; fax: +31-30-2513828</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4+ cell counts between 50 and 350 cells/μl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (>10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.</abstract><note type="content">Section title: Original article</note><note type="content">Fig. 1: Median changes from baseline of CD4 cell count per dose group. Baseline CD4 cell count is defined as the CD4 cell count of week 0 only. Patients receiving placebo during the first 12 weeks of the study were switched to delavirdine 900 mg/day at week 12. All patients received zidovudine or zidovudine/zalcitabine (zidovudine 600 mg/day, zalcitabine 2.25 mg/day) in combination with one of the dosages of delavirdine or placebo.</note><note type="content">Fig. 2: Median changes from baseline of HIV-1 RNA load. Baseline viral load was defined as log number of RNA copies of week 0 only. Patients receiving placebo during the first 12 weeks of the study were switched to delavirdine 900 mg/day at week 12. All patients received zidovudine or zidovudine/zalcitabine (zidovudine 600 mg/day, zalcitabine 2.25 mg/day) in combination with one of the dosages of delavirdine or placebo.</note><note type="content">Table 1: Entry characteristics of the treatment groups</note><note type="content">Table 2: Median susceptibility (IC50) of the clinical isolates for delavirdine and zidovudine at baseline (i.e., zidovudine monotherapy) and after 12 weeks of the combination therapy with zidovudine and delavirdine (600 mg, 1200 mg, escalating dose from 150 to 1200 mg) or continuation of zidovudine monotherapy (delavirdine placebo)</note><note type="content">Table 3: Incidence of adverse eventsa, clinical endpoints and dropouts</note><subject lang="en"><genre>Keywords</genre><topic>Delavirdine</topic><topic>HIV</topic><topic>Zidovudine</topic></subject><relatedItem type="host"><titleInfo><title>International Journal of Antimicrobial Agents</title></titleInfo><titleInfo type="abbreviated"><title>ANTAGE</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">199901</dateIssued></originInfo><identifier type="ISSN">0924-8579</identifier><identifier type="PII">S0924-8579(00)X0026-X</identifier><part><date>199901</date><detail type="volume"><number>11</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1</start><end>88</end></extent><extent unit="pages"><start>13</start><end>21</end></extent></part></relatedItem><identifier type="istex">222583409E60A1F786D16E3885AE2D79E27D7FAE</identifier><identifier type="ark">ark:/67375/6H6-JXZKHWVT-1</identifier><identifier type="DOI">10.1016/S0924-8579(98)00082-X</identifier><identifier type="PII">S0924-8579(98)00082-X</identifier><accessCondition type="use and reproduction" contentType="copyright">©1999 Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science B.V., ©1999</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/222583409E60A1F786D16E3885AE2D79E27D7FAE/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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