Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013
Identifieur interne : 000133 ( Pmc/Corpus ); précédent : 000132; suivant : 000134Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013
Auteurs : Gilles Wandeler ; Marion Schlauri ; Marie-Eve Jaquier ; Janine Rohrbach ; Karin J. Metzner ; Jan Fehr ; Juan Ambrosioni ; Matthias Cavassini ; Marcel Stöckle ; Patrick Schmid ; Enos Bernasconi ; Olivia Keiser ; Luisa Salazar-Vizcaya ; Hansjakob Furrer ; Andri RauchSource :
- Open Forum Infectious Diseases [ 2328-8957 ] ; 2015.
Abstract
In this large cohort of HIV-infected patients with an incident HCV infection, treatment uptake and outcomes improved in recent years. As a consequence, the proportion of patients with a detectable HCV viral load decreased significantly with time.
Url:
DOI: 10.1093/ofid/ofv026
PubMed: 26034775
PubMed Central: 4438905
Links to Exploration step
PMC:4438905Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013</title><author><name sortKey="Wandeler, Gilles" sort="Wandeler, Gilles" uniqKey="Wandeler G" first="Gilles" last="Wandeler">Gilles Wandeler</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Schlauri, Marion" sort="Schlauri, Marion" uniqKey="Schlauri M" first="Marion" last="Schlauri">Marion Schlauri</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Jaquier, Marie Eve" sort="Jaquier, Marie Eve" uniqKey="Jaquier M" first="Marie-Eve" last="Jaquier">Marie-Eve Jaquier</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Rohrbach, Janine" sort="Rohrbach, Janine" uniqKey="Rohrbach J" first="Janine" last="Rohrbach">Janine Rohrbach</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Metzner, Karin J" sort="Metzner, Karin J" uniqKey="Metzner K" first="Karin J." last="Metzner">Karin J. Metzner</name><affiliation><nlm:aff id="af3"><addr-line>Division of Infectious Diseases and Hospital Epidemiology</addr-line>,<institution>University Hospital Zurich, University of Zurich</institution>,</nlm:aff></affiliation></author><author><name sortKey="Fehr, Jan" sort="Fehr, Jan" uniqKey="Fehr J" first="Jan" last="Fehr">Jan Fehr</name><affiliation><nlm:aff id="af3"><addr-line>Division of Infectious Diseases and Hospital Epidemiology</addr-line>,<institution>University Hospital Zurich, University of Zurich</institution>,</nlm:aff></affiliation></author><author><name sortKey="Ambrosioni, Juan" sort="Ambrosioni, Juan" uniqKey="Ambrosioni J" first="Juan" last="Ambrosioni">Juan Ambrosioni</name><affiliation><nlm:aff id="af4"><institution>University Hospital Geneva</institution>,</nlm:aff></affiliation></author><author><name sortKey="Cavassini, Matthias" sort="Cavassini, Matthias" uniqKey="Cavassini M" first="Matthias" last="Cavassini">Matthias Cavassini</name><affiliation><nlm:aff id="af5"><institution>University Hospital Lausanne</institution>,</nlm:aff></affiliation></author><author><name sortKey="Stockle, Marcel" sort="Stockle, Marcel" uniqKey="Stockle M" first="Marcel" last="Stöckle">Marcel Stöckle</name><affiliation><nlm:aff id="af6"><institution>University Hospital Basel</institution>,</nlm:aff></affiliation></author><author><name sortKey="Schmid, Patrick" sort="Schmid, Patrick" uniqKey="Schmid P" first="Patrick" last="Schmid">Patrick Schmid</name><affiliation><nlm:aff id="af7"><institution>Cantonal Hospital</institution>,<addr-line>St. Gallen</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Bernasconi, Enos" sort="Bernasconi, Enos" uniqKey="Bernasconi E" first="Enos" last="Bernasconi">Enos Bernasconi</name><affiliation><nlm:aff id="af8"><institution>Regional Hospital</institution>,<addr-line>Lugano</addr-line>,<country>Switzerland</country></nlm:aff></affiliation></author><author><name sortKey="Keiser, Olivia" sort="Keiser, Olivia" uniqKey="Keiser O" first="Olivia" last="Keiser">Olivia Keiser</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Salazar Vizcaya, Luisa" sort="Salazar Vizcaya, Luisa" uniqKey="Salazar Vizcaya L" first="Luisa" last="Salazar-Vizcaya">Luisa Salazar-Vizcaya</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Furrer, Hansjakob" sort="Furrer, Hansjakob" uniqKey="Furrer H" first="Hansjakob" last="Furrer">Hansjakob Furrer</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Rauch, Andri" sort="Rauch, Andri" uniqKey="Rauch A" first="Andri" last="Rauch">Andri Rauch</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26034775</idno><idno type="pmc">4438905</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438905</idno><idno type="RBID">PMC:4438905</idno><idno type="doi">10.1093/ofid/ofv026</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000133</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000133</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013</title><author><name sortKey="Wandeler, Gilles" sort="Wandeler, Gilles" uniqKey="Wandeler G" first="Gilles" last="Wandeler">Gilles Wandeler</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Schlauri, Marion" sort="Schlauri, Marion" uniqKey="Schlauri M" first="Marion" last="Schlauri">Marion Schlauri</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Jaquier, Marie Eve" sort="Jaquier, Marie Eve" uniqKey="Jaquier M" first="Marie-Eve" last="Jaquier">Marie-Eve Jaquier</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Rohrbach, Janine" sort="Rohrbach, Janine" uniqKey="Rohrbach J" first="Janine" last="Rohrbach">Janine Rohrbach</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Metzner, Karin J" sort="Metzner, Karin J" uniqKey="Metzner K" first="Karin J." last="Metzner">Karin J. Metzner</name><affiliation><nlm:aff id="af3"><addr-line>Division of Infectious Diseases and Hospital Epidemiology</addr-line>,<institution>University Hospital Zurich, University of Zurich</institution>,</nlm:aff></affiliation></author><author><name sortKey="Fehr, Jan" sort="Fehr, Jan" uniqKey="Fehr J" first="Jan" last="Fehr">Jan Fehr</name><affiliation><nlm:aff id="af3"><addr-line>Division of Infectious Diseases and Hospital Epidemiology</addr-line>,<institution>University Hospital Zurich, University of Zurich</institution>,</nlm:aff></affiliation></author><author><name sortKey="Ambrosioni, Juan" sort="Ambrosioni, Juan" uniqKey="Ambrosioni J" first="Juan" last="Ambrosioni">Juan Ambrosioni</name><affiliation><nlm:aff id="af4"><institution>University Hospital Geneva</institution>,</nlm:aff></affiliation></author><author><name sortKey="Cavassini, Matthias" sort="Cavassini, Matthias" uniqKey="Cavassini M" first="Matthias" last="Cavassini">Matthias Cavassini</name><affiliation><nlm:aff id="af5"><institution>University Hospital Lausanne</institution>,</nlm:aff></affiliation></author><author><name sortKey="Stockle, Marcel" sort="Stockle, Marcel" uniqKey="Stockle M" first="Marcel" last="Stöckle">Marcel Stöckle</name><affiliation><nlm:aff id="af6"><institution>University Hospital Basel</institution>,</nlm:aff></affiliation></author><author><name sortKey="Schmid, Patrick" sort="Schmid, Patrick" uniqKey="Schmid P" first="Patrick" last="Schmid">Patrick Schmid</name><affiliation><nlm:aff id="af7"><institution>Cantonal Hospital</institution>,<addr-line>St. Gallen</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Bernasconi, Enos" sort="Bernasconi, Enos" uniqKey="Bernasconi E" first="Enos" last="Bernasconi">Enos Bernasconi</name><affiliation><nlm:aff id="af8"><institution>Regional Hospital</institution>,<addr-line>Lugano</addr-line>,<country>Switzerland</country></nlm:aff></affiliation></author><author><name sortKey="Keiser, Olivia" sort="Keiser, Olivia" uniqKey="Keiser O" first="Olivia" last="Keiser">Olivia Keiser</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Salazar Vizcaya, Luisa" sort="Salazar Vizcaya, Luisa" uniqKey="Salazar Vizcaya L" first="Luisa" last="Salazar-Vizcaya">Luisa Salazar-Vizcaya</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Furrer, Hansjakob" sort="Furrer, Hansjakob" uniqKey="Furrer H" first="Hansjakob" last="Furrer">Hansjakob Furrer</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author><author><name sortKey="Rauch, Andri" sort="Rauch, Andri" uniqKey="Rauch A" first="Andri" last="Rauch">Andri Rauch</name><affiliation><nlm:aff id="af1"><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</nlm:aff></affiliation></author></analytic><series><title level="j">Open Forum Infectious Diseases</title><idno type="eISSN">2328-8957</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In this large cohort of HIV-infected patients with an incident HCV infection, treatment uptake and outcomes improved in recent years. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Open Forum Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Open Forum Infect Dis</journal-id><journal-id journal-id-type="publisher-id">ofid</journal-id><journal-id journal-id-type="hwp">ofids</journal-id><journal-title-group><journal-title>Open Forum Infectious Diseases</journal-title></journal-title-group><issn pub-type="epub">2328-8957</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26034775</article-id><article-id pub-id-type="pmc">4438905</article-id><article-id pub-id-type="doi">10.1093/ofid/ofv026</article-id><article-id pub-id-type="publisher-id">ofv026</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles</subject></subj-group></article-categories><title-group><article-title>Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wandeler</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="author-notes" rid="AN1">a</xref></contrib><contrib contrib-type="author"><name><surname>Schlauri</surname><given-names>Marion</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">a</xref></contrib><contrib contrib-type="author"><name><surname>Jaquier</surname><given-names>Marie-Eve</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">a</xref></contrib><contrib contrib-type="author"><name><surname>Rohrbach</surname><given-names>Janine</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Metzner</surname><given-names>Karin J.</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Fehr</surname><given-names>Jan</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ambrosioni</surname><given-names>Juan</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Cavassini</surname><given-names>Matthias</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Stöckle</surname><given-names>Marcel</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Schmid</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Bernasconi</surname><given-names>Enos</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Keiser</surname><given-names>Olivia</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Salazar-Vizcaya</surname><given-names>Luisa</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Furrer</surname><given-names>Hansjakob</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rauch</surname><given-names>Andri</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><on-behalf-of>The Swiss HIV Cohort Study</on-behalf-of><aff id="af1"><label>1</label><addr-line>Department of Infectious Diseases</addr-line>,<institution>Bern University Hospital and University of Bern</institution>,</aff><aff id="af2"><label>2</label><addr-line>Institute of Social and Preventive Medicine</addr-line>,<institution>University of Bern</institution>,</aff><aff id="af3"><label>3</label><addr-line>Division of Infectious Diseases and Hospital Epidemiology</addr-line>,<institution>University Hospital Zurich, University of Zurich</institution>,</aff><aff id="af4"><label>4</label><institution>University Hospital Geneva</institution>,</aff><aff id="af5"><label>5</label><institution>University Hospital Lausanne</institution>,</aff><aff id="af6"><label>6</label><institution>University Hospital Basel</institution>,</aff><aff id="af7"><label>7</label><institution>Cantonal Hospital</institution>,<addr-line>St. Gallen</addr-line>,</aff><aff id="af8"><label>8</label><institution>Regional Hospital</institution>,<addr-line>Lugano</addr-line>,<country>Switzerland</country></aff></contrib-group><contrib-group><contrib contrib-type="collab"><collab>The Swiss HIV Cohort Study</collab></contrib><contrib contrib-type="collab"><name><surname>Aubert</surname><given-names>V.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Battegay</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Bernasconi</surname><given-names>E.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Böni</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Bucher</surname><given-names>H.C.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Burton-Jeangros</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Calmy</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Cavassini</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Dollenmaier</surname><given-names>G.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Egger</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Elzi</surname><given-names>L.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Fehr</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Fellay</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Furrer</surname><given-names>H.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Fux</surname><given-names>C.A.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Gorgievski</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Günthard</surname><given-names>H.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Haerry</surname><given-names>D.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Hasse</surname><given-names>B.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Hirsch</surname><given-names>H.H.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Hoffmann</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Hösli</surname><given-names>I.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Kahlert</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Kaiser</surname><given-names>L.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Keiser</surname><given-names>O.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Klimkait</surname><given-names>T.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Kouyos</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Kovari</surname><given-names>H.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Ledergerber</surname><given-names>B.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Martinetti</surname><given-names>G.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Martinez de Tejada</surname><given-names>B.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Metzner</surname><given-names>K.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Müller</surname><given-names>N.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Nadal</surname><given-names>D.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Nicca</surname><given-names>D.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Pantaleo</surname><given-names>G.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Rauch</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Regenass</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Rickenbach</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Rudin</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Schöni-Affolter</surname><given-names>F.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Schmid</surname><given-names>P.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Schüpbach</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Speck</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Tarr</surname><given-names>P.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Telenti</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Trkola</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Vernazza</surname><given-names>P.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Weber</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Yerly</surname><given-names>S.</given-names></name></contrib></contrib-group><author-notes><fn fn-type="con" id="AN1"><label>a</label><p>G. W., M. S., and M.-E. J. contributed equally to this work.</p></fn><corresp>Correspondence: Gilles Wandeler, MD MSc, University Hospital Bern, Inselspital, CH-3010 Bern, Switzerland (<email>gwandeler@ispm.unibe.ch</email>).</corresp></author-notes><pub-date pub-type="collection"><month>1</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>19</day><month>2</month><year>2015</year></pub-date><volume>2</volume><issue>1</issue><elocation-id>ofv026</elocation-id><history><date date-type="received"><day>3</day><month>11</month><year>2014</year></date><date date-type="accepted"><day>12</day><month>2</month><year>2015</year></date></history><permissions><copyright-statement>© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.</copyright-statement><copyright-year>2015</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link>), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="ofv026.pdf"></self-uri><abstract abstract-type="precis"><p>In this large cohort of HIV-infected patients with an incident HCV infection, treatment uptake and outcomes improved in recent years. As a consequence, the proportion of patients with a detectable HCV viral load decreased significantly with time.</p></abstract><abstract><p><bold><italic>Background.</italic></bold> The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent.</p><p><bold><italic>Methods.</italic></bold> We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up.</p><p><bold><italic>Results.</italic></bold> Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (<italic>P</italic> < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (<italic>P</italic> < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (<italic>P</italic> < .001). An SVR was achieved in 78% and 29% (<italic>P</italic> = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58–0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16–0.35) in the other group (<italic>P</italic> < .001).</p><p><bold><italic>Conclusions.</italic></bold> In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.</p></abstract><kwd-group><kwd>acute HCV</kwd><kwd>treatment outcomes</kwd><kwd>treatment uptake</kwd></kwd-group><counts><page-count count="8"></page-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>Winter 2015</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p>We recently observed dramatic changes in the hepatitis C virus (HCV) infection epidemic in the Swiss HIV Cohort Study (SHCS), including an 18-fold incidence increase in men who have sex with men (MSM) [<xref rid="OFV026C1" ref-type="bibr">1</xref>]. Hepatitis C virus infection is a major cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV) and, if left untreated, often leads to liver cirrhosis and hepatocellular carcinoma [<xref rid="OFV026C2" ref-type="bibr">2</xref>]. The long-term trends in treatment uptake and outcomes of incident HCV infections are largely unknown. Because spontaneous clearance of the virus is only seen in a minority of patients [<xref rid="OFV026C3" ref-type="bibr">3</xref>, <xref rid="OFV026C4" ref-type="bibr">4</xref>], most individuals infected with HIV with an acute HCV infection would benefit from early diagnosis and treatment. Sustained virological response (SVR) rates of 60%–80% have been observed in selected groups of patients infected with HIV if antiviral therapy with pegylated interferon (Peg-IFN) and ribavirin (RBV) was initiated within 1 year after HCV diagnosis [<xref rid="OFV026C5" ref-type="bibr">5</xref>, <xref rid="OFV026C6" ref-type="bibr">6</xref>]. However, no clinical trial comparing the success of early versus deferred HCV therapy in patients infected with HIV have been performed to date, and previous observational studies were limited by small patient numbers or restricted to outbreaks in large urban centers [<xref rid="OFV026C7" ref-type="bibr">7</xref>–<xref rid="OFV026C9" ref-type="bibr">9</xref>].</p><p>Early diagnosis of HCV infections and uptake of treatment have generally been suboptimal in most HIV clinics [<xref rid="OFV026C10" ref-type="bibr">10</xref>, <xref rid="OFV026C11" ref-type="bibr">11</xref>]. This implies that despite the availability of effective HCV therapy, the overall burden of liver disease due to HCV in patients infected with HIV remains very high and that HIV/HCV-coinfected patients can transmit HCV for many years. Thus, it is now evident that a relevant impact on global HCV transmission and HCV-related mortality will only be achieved if uptake of treatment is massively increased [<xref rid="OFV026C12" ref-type="bibr">12</xref>, <xref rid="OFV026C13" ref-type="bibr">13</xref>]. In recent years, the concept of a cascade or pyramid of care for HIV infection has attracted much attention from public health authorities, in both low- and high-income countries, and helped evaluate and improve the progress of HIV care [<xref rid="OFV026C14" ref-type="bibr">14</xref>, <xref rid="OFV026C15" ref-type="bibr">15</xref>]. The evaluation of HCV care and treatment programs with a similar approach would help identify the most important gaps in HCV management and inform future strategies and policies regarding HCV management.</p><p>We studied the natural history and treatment uptake of all incident HCV infections between 1991 and 2012 in a nationwide HIV cohort and compared HCV treatment outcomes between patients who experienced a seroconversion before and after the first description of the surging epidemic among MSM in 2005 [<xref rid="OFV026C16" ref-type="bibr">16</xref>–<xref rid="OFV026C18" ref-type="bibr">18</xref>]. We also intended to show the impact of early treatment on the pyramid of HCV care and the proportion of the population with a detectable viral load.</p><sec sec-type="methods" id="s2"><title>METHODS</title><sec id="s2a"><title>Swiss HIV Cohort Study</title><p>The SHCS (<uri xlink:type="simple" xlink:href="www.shcs.ch">www.shcs.ch</uri>) is a prospective nationwide cohort study with ongoing enrollment of adults infected with HIV in Switzerland since 1988. It covers approximately 50% of the cumulative number of HIV infections declared to the Swiss public health authorities and 75% of patients receiving antiretroviral therapy (ART) in Switzerland [<xref rid="OFV026C19" ref-type="bibr">19</xref>]. Detailed information on demographics, mode of HIV acquisition, risk behavior, clinical events, coinfections, and treatment is collected using a standard protocol at registration and then at 6-month intervals. All participants are screened for HCV infection at study entry. Since 1998, HCV serology is repeated at least every 24 months in all patients. Local ethical committees of all participating study sites have approved the study, and written consent has been obtained from all participants.</p></sec><sec id="s2b"><title>Inclusion Criteria and Definitions</title><p>All patients with a documented HCV seroconversion before June 2012 and a follow-up of at least 6 months thereafter were considered. Patients who had a single positive anti-HCV antibody test but a negative immunoblot, no positive RNA measurement, and negative follow-up anti-HCV antibody tests were classified as false-positives and excluded from the analyses. Natural history and treatment outcomes were defined as follows: spontaneous clearance, single negative HCV viral load after a confirmed incident infection without any HCV treatment; SVR, undetectable HCV RNA 6 months after completion of HCV treatment; persistent infection, detectable HCV RNA at least 1 year after diagnosis of incident HCV infection; reinfection, either an HCV genotype switch after a first infection or a newly detectable HCV viral load after spontaneous clearance or treatment-induced SVR; early infection, within 12 months of HCV diagnosis. The latter definition takes into account previous studies that demonstrated that high SVR are achieved if HCV treatment is started within the first year after seroconversion [<xref rid="OFV026C6" ref-type="bibr">6</xref>].</p></sec><sec id="s2c"><title>Data Collection</title><p>In addition to the individual data collected routinely within the framework of the SHCS, we performed medical chart reviews to collect detailed information on HCV diagnosis, natural history, and treatment using standardized case report forms. The reasons (from the provider's perspective) for not starting HCV treatment, as well as symptoms and side-effects leading to an HCV treatment interruption or dosage adaptation, were also retrieved. Furthermore, all additional HCV viral load and transaminase measurements were included. <italic>IL28B</italic> genotypes were determined using TaqMan Genotyping Master Mix (Life Technologies, Carlsbad, CA), as described previously [<xref rid="OFV026C20" ref-type="bibr">20</xref>].</p></sec><sec id="s2d"><title>Statistical Analyses</title><p>Baseline demographic and clinical characteristics at time of HCV seroconversion were described using absolute numbers and proportions, or medians and interquartile ranges, and were compared between time periods (before and after January 1, 2006) using the χ<sup>2</sup>, Fisher's exact, or Mann–Whitney <italic>U</italic> test, where appropriate. January 2006 was chosen because by then the first reports on the possible sexual transmission of HCV in MSM in Europe had been published, and the awareness of this epidemiological trend among physicians and public health authorities was increasing in Switzerland [<xref rid="OFV026C16" ref-type="bibr">16</xref>–<xref rid="OFV026C18" ref-type="bibr">18</xref>, <xref rid="OFV026C21" ref-type="bibr">21</xref>]. Similarly, natural history as well as treatment uptake were compared between time periods. Hepatitis C virus therapy outcomes were compared between patients who received treatment during the first year after seroconversion (“early infection”) and the others. Kaplan–Meier analyses were used to compare the probability of HCV suppression over time between patients diagnosed before and after 2006. For the latter analysis, follow-up was censored at first HCV suppression, death, or drop out, whichever happened first. This analysis included only follow-up time after 2002 because HCV viral load measurements were infrequent before that year. All statistical analyses were performed using Stata 12.0 (Stata Corp, College Station, TX) and R version 3.0.2 with the survival and ggplot2 (<uri xlink:type="simple" xlink:href="http://cran.r-project.org/web/packages/ggplot2/index.html">http://cran.r-project.org/web/packages/ggplot2/index.html</uri>) and survival (<uri xlink:type="simple" xlink:href="http://cran.r-project.org/web/packages/survival/index.html">http://cran.r-project.org/web/packages/survival/index.html</uri>) special packages.</p></sec></sec><sec sec-type="results" id="s3"><title>RESULTS</title><sec id="s3a"><title>Patient Characteristics</title><p>Of 237 patients with a newly positive screening HCV serology, 34 were considered false-positives and 203 were HCV seroconversions. Ten additional patients were excluded due to insufficient information. The baseline demographic and clinical characteristics of the 193 patients included in our analyses are shown in Table <xref ref-type="table" rid="OFV026TB1">1</xref>. One hundred six patients were diagnosed with an incident HCV infection before 2006, and 87 patients were diagnosed after January 2006. Patients with incident infections diagnosed from 2006 onwards were more likely to be MSM (85% vs 24%, <italic>P</italic> < .001) and to be on ART (94% vs 76%, <italic>P</italic> < .001) compared with individuals diagnosed before 2006. Of 64 HCV infections in people who inject drugs (PWID), only 4 were diagnosed after 2006. Patients with acute HCV infections after 2006 had a higher sexual risk behavior than those diagnosed in earlier years: the proportion with inconsistent condom use (78% vs 33%, <italic>P</italic> < .001), occasional sexual partners (84% vs 26%, <italic>P</italic> < .001), and history of syphilis (45% vs 7%, <italic>P</italic> < .001) was higher after 2006. Hepatitis C virus genotype 1 was more frequent after 2006 (57% vs 49%), whereas the proportion of genotype 3 infections decreased after January 2006 (19% vs 25% before 2006). The proportion of genotype 4 infections remained stable over time, and only 3 patients had a genotype 2 infection.
<table-wrap id="OFV026TB1" position="float"><label>Table 1.</label><caption><p>Characteristics of Patients With Incident HCV Infection in the Swiss HIV Cohort Study at Time of Diagnosis</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="char" char="(" span="1"></col><col align="char" char="." span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Characteristic</th><th align="left" rowspan="1" colspan="1">Diagnosis Before Jan 2006 (n = 106)</th><th align="left" rowspan="1" colspan="1">Diagnosis During or After Jan 2006 (n = 87)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">Female sex (%)</td><td rowspan="1" colspan="1">29 (27.4)</td><td rowspan="1" colspan="1">4 (4.6)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">Median age in years (IQR)</td><td rowspan="1" colspan="1">31 (28–39)</td><td rowspan="1" colspan="1">34 (30–40)</td><td rowspan="1" colspan="1">.03</td></tr><tr><td rowspan="1" colspan="1">Median CD4 in cells/μL (IQR)</td><td rowspan="1" colspan="1">363 (220–613)</td><td rowspan="1" colspan="1">507 (359–675)</td><td rowspan="1" colspan="1">.001</td></tr><tr><td rowspan="1" colspan="1">On ART (%)</td><td rowspan="1" colspan="1">80 (75.5)</td><td rowspan="1" colspan="1">82 (94.3)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">Suppressed HIV VL (%)</td><td rowspan="1" colspan="1">58 (54.7)</td><td rowspan="1" colspan="1">69 (79.3)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">Occasional sexual partners (%)</td><td rowspan="1" colspan="1">27 (25.5)</td><td rowspan="1" colspan="1">73 (83.9)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">Inconsistent condom use (%)</td><td rowspan="1" colspan="1">35 (33.0)</td><td rowspan="1" colspan="1">68 (78.2)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">History of syphilis (%)</td><td rowspan="1" colspan="1">7 (6.6)</td><td rowspan="1" colspan="1">39 (44.8)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">HIV transmission group (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1"> MSM</td><td rowspan="1" colspan="1">25 (23.6)</td><td rowspan="1" colspan="1">74 (85.1)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> PWID</td><td rowspan="1" colspan="1">60 (56.6)</td><td rowspan="1" colspan="1">4 (4.6)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> HET</td><td rowspan="1" colspan="1">15 (14.2)</td><td rowspan="1" colspan="1">7 (8.1)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Other</td><td rowspan="1" colspan="1">6 (5.7)</td><td rowspan="1" colspan="1">2 (2.3)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">HCV genotype (n = 136)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">.01</td></tr><tr><td rowspan="1" colspan="1"> 1</td><td rowspan="1" colspan="1">34 (49.3)</td><td rowspan="1" colspan="1">38 (56.7)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> 2</td><td rowspan="1" colspan="1">2 (2.9)</td><td rowspan="1" colspan="1">1 (1.5)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> 3</td><td rowspan="1" colspan="1">17 (24.6)</td><td rowspan="1" colspan="1">13 (19.4)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> 4</td><td rowspan="1" colspan="1">16 (23.2)</td><td rowspan="1" colspan="1">15 (22.4)</td><td rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="TN1"><p>Abbreviations: ART, antiretroviral therapy; HCV, hepatitis C infection; HET, heterosexual; HIV, human immunodeficiency virus; IQR, interquartile range; MSM, men who have sex with men; PWID, people who inject drugs; VL, viral load.</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="s3b"><title>Natural Course and Treatment Uptake</title><p>A spontaneous clearance was observed in 48 cases (32% of those not treated during acute infection) (Figure <xref ref-type="fig" rid="OFV026F1">1</xref>). Treatment uptake changed over time, with a major increase from 2006 onwards (<ext-link ext-link-type="uri" xlink:href="http://ofid.oxfordjournals.org/lookup/suppl/doi:10.1093/ofid/ofv026/-/DC1">Supplementary Figure 1</ext-link>). Overall, 49 patients (25%) were treated during the early phase of HCV infection, and 96 patients (50%) progressed to chronic HCV infection. Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (<italic>P</italic> < .001). Among those treated, only 22% (6 patients, including 3 MSM) started treatment during early infection before 2006, compared with 91% (43 patients, including 40 MSM) after 2006 (<italic>P</italic> < .001). Among patients without spontaneous clearance, HCV treatment uptake was higher in MSM compared with PWID before (21% vs 0%) and after 2006 (71% vs 50%). Of 96 patients with persistent infection, only 25 (26%) were treated during follow-up. The most frequent reasons for patients diagnosed before 2006 not to be treated were “persistent alcohol or drug abuse” (25%), followed by “patient's refusal” (21%). After 2006, “other psychiatric comorbidities” and “waiting for new direct-acting antivirals (DAAs)” became additional important reason for not starting therapy (20% each). Past noninjecting drug use was not a barrier for early HCV therapy: for patients diagnosed after 2006, it was reported in 56% of patients with early HCV therapy, compared with 44% in those with spontaneous clearance and 47% in patients who were not treated for HCV. Overall, 11 patients experienced an HCV reinfection, including 9 MSM and 2 PWID. Of these, 6 patients (all MSM) had a reinfection after a treatment-induced SVR, and 5 patients had a reinfection after spontaneous clearance. In total, 23 (12%) patients died during follow-up.
<fig id="OFV026F1" position="float"><label>Figure 1.</label><caption><p>Natural course of hepatitis C virus (HCV) infection and treatment uptake in HIV-infected patients with incident HCV infection before (A) and after (B) January 2006.</p></caption><graphic xlink:href="ofv02601"></graphic></fig></p></sec><sec id="s3c"><title>Treatment Outcomes</title><p>Seventy of 74 treated patients had an available treatment outcome at time of database closure and were included in this analysis. All patients were treated with Peg-IFN and RBV, but DAAs were not used. An SVR was achieved in 78% and 29% (<italic>P</italic> = .01) of patients treated during early and chronic HCV infection, respectively (Figure <xref ref-type="fig" rid="OFV026F2">2</xref>). In patients treated during early HCV infection, SVR was high irrespective of the <italic>IL28B</italic> genotype (19 of 25 [76%] in C/C and 16 of 20 [80%] in non-C/C genotypes), whereas SVR differed between <italic>IL28B</italic> genotypes in those treated during chronic infection (3 of 6 [50%] vs 4 of 16 [25%] in CC and non-CC, respectively). Among patients treated during early infection, there was no significant difference in SVR rates between genotypes: genotype 1, 17 of 26 (65%); genotype 2, 2 of 2 (100%); genotype 3, 8 of 8 (100%); genotype 4, 7 of 8 (88%) (<italic>P</italic> = .14). Of 46 patients treated during the early phase of infection, only 9 (20%) experienced a relapse or a nonresponse, whereas this proportion reached 50% in those treated during the chronic phase of infection.
<fig id="OFV026F2" position="float"><label>Figure 2.</label><caption><p>Hepatitis C virus (HCV) treatment outcomes by stage of infection. Abbreviation: SVR, sustained virological response.</p></caption><graphic xlink:href="ofv02602"></graphic></fig></p></sec><sec id="s3d"><title>Pyramid of Care and Population Effect</title><p>Before 2006, only 33% of patients without spontaneous clearance of HCV were treated for their HCV infection, and 12% patients achieved a treatment-induced SVR overall (Figure <xref ref-type="fig" rid="OFV026F3">3</xref>). If the 23 patients with a spontaneous clearance were added to this estimation, the overall proportion with a resolved infection in this time period was 31%. In comparison, after 2006, 77% of patients without a spontaneous clearance were treated, and 53% achieved a SVR. Adding the 25 spontaneous clearances during this period resulted in an overall proportion of individuals with a resolved infection reaching 67%. Figure <xref ref-type="fig" rid="OFV026F4">4</xref>A shows the Kaplan–Meier curves of HCV viral load detectability by time period, over a total of 706 person-years of follow-up. The 5-year probability of having a detectable viral load was 0.67 (95% confidence interval [CI], 0.58–0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16–0.35) in the other group (log rank test; <italic>P</italic> < .001). The overall proportion of patients with a detectable HCV viral load in the cohort decreased over time, from 0.95 (95% CI, 0.84–0.98) in 2002 to 0.70 (95% CI, 0.61–0.77) in 2012 (Figure <xref ref-type="fig" rid="OFV026F4">4</xref>B). The full picture of individual HCV viral loads over time in the whole cohort is shown in <ext-link ext-link-type="uri" xlink:href="http://ofid.oxfordjournals.org/lookup/suppl/doi:10.1093/ofid/ofv026/-/DC1">Supplementary Figure 2</ext-link>.
<fig id="OFV026F3" position="float"><label>Figure 3.</label><caption><p>Pyramid of care for incident hepatitis C virus (HCV) infections in the Swiss HIV Cohort Study. (Patients with spontaneous clearance of HCV have been excluded from this analysis.) Abbreviation: SVR, sustained virological response.</p></caption><graphic xlink:href="ofv02603"></graphic></fig><fig id="OFV026F4" position="float"><label>Figure 4.</label><caption><p>Impact of treatment uptake on cumulative probability of having a detectable hepatitis C virus (HCV) viral load (A) and on the proportion in patients with incident HCV infections (B)</p></caption><graphic xlink:href="ofv02604"></graphic></fig></p></sec></sec><sec sec-type="discussion" id="s4"><title>DISCUSSION</title><p>In this nationwide cohort of patients infected with HIV with an incident HCV infection, overall treatment uptake during early infection was low, but it improved after 2006, the year after the dissemination of the first reports on sexual transmission of HCV in HIV-infected MSM. After 2006, 85% of acute HCV infections were observed in MSM. These patients were much more likely to be treated during early stages of infection compared with patients diagnosed before 2006, who were mainly PWID. In HCV infections treated during the first year after diagnosis, an SVR was reached in 78% of cases, compared with only 29% in those treated during chronic infection. Improved treatment uptake after 2006 led to a continuous decrease in the overall proportion of patients with a detectable HCV viral load.</p><p>Trends in the epidemiology of HCV infections among patients infected with HIV are rapidly evolving. This nationwide observational study underlines these changes, because the proportion of MSM in acute HCV infections increased from 24% before 2006 to 85% after 2006. We previously showed that this increase was associated with high-risk sexual behavior, including a history of past syphilis infection [<xref rid="OFV026C1" ref-type="bibr">1</xref>]. The present study highlights the dramatic change in sociobehavioral trends of the population affected by the HCV epidemic: from mainly PWID before 2006 to MSM with stable HIV infections under ART but poor condom use and frequent occasional partners after January 2006.</p><p>Hepatitis C virus therapy outcomes with Peg-IFN and RBV are improved when treatment is started during the early phase of infection, as shown in large trials of HCV-monoinfected patients [<xref rid="OFV026C22" ref-type="bibr">22</xref>] and in several observational studies in cohorts of patients infected with HIV [<xref rid="OFV026C7" ref-type="bibr">7</xref>, <xref rid="OFV026C8" ref-type="bibr">8</xref>]. Our results confirm these findings, because 78% of the patients treated within the first year after HCV seroconversion achieved an SVR. This estimate was slightly higher than what was observed in a multicenter European cohort study (62% SVR) [<xref rid="OFV026C7" ref-type="bibr">7</xref>]. In accordance with the results from a large HIV cohort collaboration [<xref rid="OFV026C23" ref-type="bibr">23</xref>], <italic>IL28B</italic> genotype did not have an impact on acute HCV treatment outcomes in the SHCS.</p><p>Early HCV diagnosis and treatment uptake are 2 of the most important bottlenecks towards the eradication of HCV infection [<xref rid="OFV026C12" ref-type="bibr">12</xref>, <xref rid="OFV026C13" ref-type="bibr">13</xref>, <xref rid="OFV026C24" ref-type="bibr">24</xref>]. Treatment uptake for acute and chronic HCV infections has been consistently poor in most settings. In a single center of the SHCS, only 8% of the patients chronically infected started treatment with Peg-IFN and RBV by 2005 [<xref rid="OFV026C10" ref-type="bibr">10</xref>]. In the present study, we showed that before 2006, only a minority of patients with an acute HCV infection was treated accordingly. However, we observed a dramatic improvement in treatment uptake after 2006: three quarters of acute HCV infections were treated, including a large majority at an early stage of infection, leading to a 2-fold increase in the overall proportion of patients with a resolved infection in recent years. The reports on the high cure rates that can be achieved if treatment is started during acute infection were the rationale for starting treatment before chronic HCV infection was established [<xref rid="OFV026C25" ref-type="bibr">25</xref>]. However, there are several additional reasons for this major increase in treatment uptake: the most obvious one is the recent changes in the characteristics of the populations infected with an acute HCV. Treating MSM under stable ART and living in good socioeconomic situations is often seen as being easier to implement compared with the management of PWID in unstable conditions. This is in part reflected by the reasons for failing to initiate HCV therapy in our study; as expected, these reasons changed over time, mainly due to the comorbidities of the risk population. Continuous substance abuse, an important issue in assessing treatment eligibility in PWID, was replaced by other psychiatric comorbidities in the most frequent reason for not starting HCV therapy as an increasing number of noninjecting MSM became infected. This underlines the need for the ongoing optimal appraisal of psychiatric comorbidities in all HIV/HCV-coinfected patients and gives rise to the hope that this barrier will be less important in the context of HCV treatment with new DAAs. However, several reports demonstrated that HCV therapy is feasible despite ongoing substance abuse and, in light of its individual and public health benefits, should not be withheld in patients willing to initiate anti-HCV therapy [<xref rid="OFV026C26" ref-type="bibr">26</xref>]. Unlike in MSM, none of the PWID in our study had a reinfection after treatment-induced clearance, which supports evidence from other settings [<xref rid="OFV026C27" ref-type="bibr">27</xref>] and further underscores the benefit of HCV therapy in this population. Another explanation for the increase in HCV treatment uptake may be the improvement of the awareness of physicians regarding the diagnosis and treatment of acute HCV infection since the description of the first HCV epidemics in MSM.</p><p>This study is the first one to describe national long-term trends in acute HCV treatment uptake and efficacy among patients infected with HIV. It relies on detailed data from routine monitoring and review of the medical charts of all patients, including information on follow-up virological assessments and reasons for not receiving HCV treatment. However, a substantial number of patients had to be excluded because of possible false-positive HCV serology results, which could not be confirmed by RNA measurements or immunoblot. This might have led to the exclusion of patients with rapid spontaneous HCV clearance and negative HCV follow-up serology and, as a consequence, to an underestimation of the number of acute HCV infections. Reinfections were identified using the SHCS database complemented by review of patient charts including transaminase levels and HCV RNA measurements. However, we cannot exclude that some reinfections were not recognized if transaminase levels had normalized before the next follow-up visits, which are typically performed every 3 months. In contrast, patients with fluctuating HCV viral loads after infection who ultimately progressed to chronic infection could have been misclassified as reinfected, which could have led to an overestimation of the rate of reinfections. Furthermore, the reason for not receiving any HCV therapy was not found in approximately one third of the patients with a chronic, untreated HCV infection.</p><p>In analogy to the reduction of acquired immune deficiency syndrome-related mortality in the context of the rapid scale up of ART, a significant impact on HCV-related mortality will only be achieved with a massive improvement in the diagnosis and treatment uptake of HCV infection. In the HIV field, the continuous assessment of the cascade of care, including HIV diagnosis, ART coverage, and efficacy, has allowed the adaption and improvement of public health policies and strategies. Likewise, it is of primary importance to evaluate the pyramid of care in terms of HCV infection management and compare results across cohorts, settings, and countries. Our study is the first one to describe such a pyramid of care for incident HCV infections in a nationwide cohort of individuals infected with HIV. In future work, the proportion of patients with an undetectable HCV viral load should be used as an important measure of HCV treatment success, in analogy to the proportion of patients with an undetectable HIV viral load in HIV programs.</p></sec><sec sec-type="conclusions" id="s5"><title>CONCLUSION</title><p>In the context of the increasing burden of liver-related morbidity and mortality in HIV-infected individuals, the improvement of HCV treatment uptake is of high priority. In the SHCS, HCV treatment uptake during the early phase of HCV infection improved over the years, leading to a 2-fold increase in the proportion of patients with a resolved HCV infection in the cohort. Even though most recent infections were diagnosed in MSM with stable HIV infections, there remained important barriers for treatment initiation including the presence of psychiatric comorbidities. The increasing availability of new IFN-free combinations will reduce the impact of these treatment barriers. Nevertheless, it is necessary to continue the efforts in terms of early diagnosis and treatment uptake if HCV-related complications are to be reduced. Eradicating HCV infection dramatically reduces the risk of liver-related death in patients infected with HIV [<xref rid="OFV026C28" ref-type="bibr">28</xref>] and prevents further HCV transmissions. As we demonstrate here, improvements in treatment uptake and efficacy substantially reduce the burden of replicating hepatitis C among patients with incident HCV infections. Our study demonstrates that frequent screening in clinical routine settings, early diagnoses, and treatment of HCV infections in persons with continued risk of infection are highly efficient interventions to reduce the burden of HCV disease at both the individual and the population level.</p></sec><sec sec-type="supplementary-material" id="s6"><title>Supplementary Material</title><p><ext-link ext-link-type="uri" xlink:href="http://ofid.oxfordjournals.org/lookup/suppl/doi:10.1093/ofid/ofv026/-/DC1">Supplementary material</ext-link> is available online at <italic>Open Forum Infectious Diseases</italic> (<uri xlink:type="simple" xlink:href="http://OpenForumInfectiousDiseases.oxfordjournals.org/">http://OpenForumInfectiousDiseases.oxfordjournals.org/</uri>).</p><supplementary-material id="PMC_1" content-type="local-data"><caption><title>Supplementary Data</title></caption><media mimetype="text" mime-subtype="html" xlink:href="supp_2_1_ofv026__index.html"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="msword" xlink:href="supp_ofv026_ofv026supp.docx"></media></supplementary-material></sec></body><back><ack><title>Acknowledgments</title><p>We thank all patients, doctors, and nurses associated with the Swiss HIV Cohort Study (SHCS). Members of the Swiss HIV Cohort Study: Aubert V, Battegay M, Bernasconi E, Böni J, Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Furrer H (Chairman of the Clinical and Laboratory Committee), Fux CA, Gorgievski M, Günthard H (President of the SHCS), Haerry D (deputy of “Positive Council”), Hasse B, Hirsch HH, Hoffmann M, Hösli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kouyos R, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Metzner K, Müller N, Nadal D, Nicca D, Pantaleo G, Rauch A (Chairman of the Scientific Board), Regenass S, Rickenbach M (Head of Data Centre), Rudin C (Chairman of the Mother & Child Substudy), Schöni-Affolter F, Schmid P, Schüpbach J, Speck R, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S.</p><p><bold><italic>Author contributions.</italic></bold> G. W. and A. R. designed the study. M. S., M.-E. J., and J. R. conducted the medical chart review. G. W., M. S., M.-E. J., J. R., L. S.-V., and A. R. performed the statistical analyses. G. W., M. S., M.-E. J., and A. R. wrote the first draft of the manuscript. All authors contributed to the interpretation of the data, critically revised the paper, and approved its final version.</p><p><bold><italic>Disclaimer.</italic></bold> The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p><p><bold><italic>Financial support.</italic></bold> This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (SNF grant #148522), by the SNF grant #146143 and SHCS project #726. G.W. was supported by an Ambizione-PROSPER fellowship from the Swiss National Science Foundation (PZ00P3_154730). 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