title: Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study.
abstract: BACKGROUND
  Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection.
  
  
  METHODS
  We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678.
  
  
  RESULTS
  Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen.
  
  
  CONCLUSIONS
  Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1-4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population.
  
  
  BACKGROUND
  Gilead Sciences.
authors: University of Paris Diderot, Paris 7 and Department of Infectious Diseases, Saint-Louis Hospital, Paris, France. Electronic address: jean-michel.molina@sls.aphp.fr.
authors: Jean-Michel
authors: JM
authors: Molina
authors: Barts Health National Health Service Trust, London, UK.
authors: Chloe
authors: C
authors: Orkin
authors: Infectious Diseases Unit, Alfred Hospital, Melbourne, VIC, Australia.
authors: David M
authors: DM
authors: Iser
authors: HIV Unit, Internal Medicine Service, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: Francisco-Xavier
authors: FX
authors: Zamora
authors: Chelsea and Westminster Hospital, St Stephens Centre, London, UK.
authors: Mark
authors: M
authors: Nelson
authors: Infectious Diseases Unit at Medical Department, Hospital of the Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors: Christoph
authors: C
authors: Stephan
authors: Gilead Sciences, Foster City, CA, USA.
authors: Benedetta
authors: B
authors: Massetto
authors: Gilead Sciences, Foster City, CA, USA.
authors: Anuj
authors: A
authors: Gaggar
authors: Gilead Sciences, Foster City, CA, USA.
authors: Liyun
authors: L
authors: Ni
authors: Gilead Sciences, Foster City, CA, USA.
authors: Evguenia
authors: E
authors: Svarovskaia
authors: Gilead Sciences, Foster City, CA, USA.
authors: Diana
authors: D
authors: Brainard
authors: Gilead Sciences, Foster City, CA, USA.
authors: G Mani
authors: GM
authors: Subramanian
authors: Gilead Sciences, Foster City, CA, USA.
authors: John G
authors: JG
authors: McHutchison
authors: Division of Infectious Diseases, AO Ospedale Niguarda Ca' Granda, Milan, Italy.
authors: Massimo
authors: M
authors: Puoti
authors: Department of General Internal Medicine I, University Hospital of Bonn, Bonn, Germany.
authors: Jürgen K
authors: JK
authors: Rockstroh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir