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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003ENew treatment regimens utilizing combinations of protease (nonstructural protein 3-4A [NS3-4A]), nucleotide (NS5B), nonnucleoside (NS5B), and NS5A inhibitors are successfully being used to treat patients with hepatitis C virus coinfected with HIV. Sustained virologic response rates of \u2265\u200590% are achieved after 12 to 24 weeks in patients with and without cirrhosis who are treatment na\u00efve and experienced. HIV is no longer a predictor of poorer response to hepatitis C virus therapy.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ehepatitis C virus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egenotypes\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efibrosis\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esustained virologic response\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eantiretroviral therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecoinfectious diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehepatic decomposition\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egastroenterology guidelines\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003ENancy S. Reau, MD, The University of Chicago Medicine, Chicago, Illinois, USA, reviewed the current treatment regimens and guidelines for hepatitis C virus (HCV) and their indications. Dr Reau was a member of the panel that developed the web-based \u201cRecommendations for Testing, Managing, and Treating Hepatitis C\u201d for the American Society for the Study of Liver Disease\/Infectious Diseases Society of America (AASLD\/IDSA) [\u003Ca href=\u0022http:\/\/www.hcvguidelines.org\u0022\u003Ewww.hcvguidelines.org\u003C\/a\u003E. Accessed May 26, 2015].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EClinical evidence supports treatment for all patients with chronic HCV (class I, level A). According to the AASLD\/IDSA guidelines, the aim is to reduce all-cause mortality and liver-related adverse events by achieving a virologic cure as evidenced by sustained virologic response (SVR). First priority should be given to persons who will derive the most benefit and have the greatest impact on further HCV transmission, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), liver transplant recipients, patients with severe extrahepatic manifestations of HCV, and those in high-risk groups where there is a potential to spread HCV (eg, men who have sex with men with high-risk sexual practices, active injection drug users, incarcerated persons, and HCV-infected women of child-bearing potential wishing to get pregnant). There are several classes of HCV therapy, each with products that have been approved or are in review with the FDA (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16794\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16794\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16794\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EAvailable Hepatitis C Virus Agents\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EThe choice of therapy for HCV is based on fibrosis stage (presence or absence of cirrhosis, compensated or decompensated), treatment experience (experienced or na\u00efve and exposure to direct acting antiviral containing medications), and subtype of HCV genotype. All oral therapy is recommended, but the combination of agents and duration of treatment will vary by genotype 1 subtype and degree of fibrosis. Interferon-based regimens are not recommended for any genotype 1 patient population. Treatment outcomes based on SVR are shown in \u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E for genotypes 1, 4, 5, and 6.\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16795\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16795\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16795\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ETreatments for HCV\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-18\u0022\u003EThe FUSION study [Jacobson IM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2013] showed that for patients with HCV genotype 2, treatment with sofosbuvir (SOF) plus ribavirin (RBV) for 12 weeks, with an extension to 16 weeks, was effective for those with cirrhosis and those who had failed prior therapy.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EThere are 2 options for patients with HCV genotype 3. Most patients should receive SOF plus RBV for 24 weeks (class I, level B), although an alternative could be SOF plus RBV plus peginterferon for 12 weeks (class IIa, level A).\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003ESusanna Naggie, MD, MHS, Duke Clinical Research Institute, Durham, North Carolina, USA, discussed the current management strategy according to the AASLD\/IDSA recommendations for patients coinfected with HCV and HIV [\u003Ca href=\u0022http:\/\/www.hcvguidelines.org\u0022\u003Ewww.hcvguidelines.org\u003C\/a\u003E. Accessed May 26, 2015].\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003EAbout 4 to 5 million individuals worldwide are coinfected with HCV\/HIV [Rotman Y, Liang TJ. \u003Cem\u003EJ Virol\u003C\/em\u003E. 2009], and about 30% of patients in the United States with HIV also have HCV [Lo Re V III et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E. 2014]. According to Dr Naggie, there are excellent data to indicate that HIV is a risk factor for transmission of HCV. For this reason, the AASLD\/IDSA HCV guidelines now recommend annual testing for high-risk HIV positive patients, such as those who inject drugs and for seropositive men who have unprotected sex with men (class IIA, level C).\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003EIn addition to clearly affecting the risk of sexual transmission of HCV, HIV affects the natural history of HCV. Despite receiving antiretroviral therapy, patients coinfected with HIV and HCV progress more quickly to decompensation than do HCV-monoinfected patients [Lo Re V III et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E. 2014]. Coinfected patients should receive the same treatment as those without HIV (class I; level B).\u003C\/p\u003E\u003Cp id=\u0022p-23\u0022\u003EDr Naggie noted that the treatment paradigm for HCV has changed in a very short period. New combinations are being developed based on the genetic barrier to resistance of the chosen regimen. Effectively stopping a rapidly replicating and mutating virus such as HCV requires a high genetic barrier. This can be achieved either by the drug (eg, nucleotide analog), which has a high genetic barrier because it binds to the conserved catalytic site of the enzyme, or by combining more direct-acting antivirals, thereby increasing the overall barrier of the regimen.\u003C\/p\u003E\u003Cp id=\u0022p-24\u0022\u003EThe effectiveness of therapy for coinfected patients has been shown in several studies using a variety of treatment regimens. SVR rates were high among coinfected patients treated with the 3D regimen (ie, 3 direct-acting antivirals) of ombitasvir, paritaprevir boosted with ritonavir, and dasabuvir for 12 or 24 weeks and regardless of treatment experience [Sulkowski MS et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2015].\u003C\/p\u003E\u003Cp id=\u0022p-25\u0022\u003EIn what is perhaps the largest trial to date of all oral direct-acting antiviral regimens in coinfected patients, the once-daily treatment with the single-tablet regimen of ledipasvir (LDV)\/SOF for 12 weeks was found to be highly effective and well tolerated in genotype 1 or 4 HCV\/HIV coinfected patients who were treatment na\u00efve and experienced, including those with cirrhosis [Naggie S et al. CROI 2015 (abstr 152LB)].\u003C\/p\u003E\u003Cp id=\u0022p-26\u0022\u003EThe ALLY-2 study found that once-daily oral daclatasvir plus SOF was associated with high SVR rates in coinfected patients with HCV genotypes 1 to 6. Although drug interactions exist with daclatasvir and HIV antiretrovirals, the lack of a fixed-dose combination with this regimen allows for the adjustment of the daclatasvir dose depending on the antiretroviral regimen used, making it a broadly compatible regimen in this population [Wyles D et al. CROI 2015 (abstr 151LB)].\u003C\/p\u003E\u003Cp id=\u0022p-27\u0022\u003EIn the ION-3 study [Kowdley KV et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2014], a fixed-dose combination tablet containing LDV\/SOF for 8 weeks was associated with a high rate of SVR among previously untreated patients with HCV genotype 1 infection without cirrhosis; however, this arm did have significantly higher relapse rates as compared with the 12-week arm. Although a post hoc analysis suggested that patients with baseline HCV RNA \u0026lt;\u20056\u2005000\u2005000 IU\/mL have a similarly low relapse rate regardless of length of treatment, this may not apply to other populations outside of this trial.\u003C\/p\u003E\u003Cp id=\u0022p-28\u0022\u003EThe ALLY-2 [Wyles D et al. CROI 2015 (abstr 151LB)] study also included an 8-week arm, and although this arm included cirrhotics and treatment-experienced patients, the SVR was significantly lower (75.6%) due to higher relapse than for those treated for 12 weeks (96.4%). Furthermore, the recent OPTIMIST-1 presentation at the 2015 meeting of the European Association for the Study of the Liver\u2014which investigated another oral regimen of simeprevir and SOF for 8 vs 12 weeks in patients without cirrhosis who were treatment na\u00efve and experienced\u2014similarly reported higher relapse in the 8-week treatment arm, although in this case the most predictive baseline HCV RNA was \u0026lt;\u20054\u2005000\u2005000 IU\/mL. Due to the higher relapse rates in 8-week treatments with current therapies and the lack of an accurate single baseline predictor, 8 weeks of LDV\/SOF or daclatasvir\/SOF is not recommended for HIV\/HCV patients.\u003C\/p\u003E\u003Cp id=\u0022p-29\u0022\u003ERecent data presented at the 2015 meeting of the European Association for the Study of the Liver showed similar rates of SVR among patients treated with grazoprevir plus elbasvir for 12 weeks who were cirrhotic and noncirrhotic, genotype 1a and 1b, and mono- and coinfected [Rockstroh JK et al. EASL 2015 (poster P0887); Zeuzem S et al EASL 2015 (abstr G07)].\u003C\/p\u003E\u003Cp id=\u0022p-30\u0022\u003EDr Naggie concluded that although SOF has few interactions, it is not sufficient alone to treat coinfected HCV\/HIV patients; these patients need a regimen that is most compatible with their antiretroviral therapy. All direct-acting antivirals have drug interactions with HIV antiretrovirals; however, with similar efficacy and safety, there should be no coinfected patient without a safe HCV treatment option. For the rare patient where that might have been the case, the pending approval of daclatasvir should provide a bailout.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/14\/25.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlhy1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlhy1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}