title: Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection.
abstract: OBJECTIVE
  Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon.
  
  
  OBJECTIVE
  To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment.
  
  
  METHODS
  Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants.
  
  
  METHODS
  Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks.
  
  
  METHODS
  The primary study outcome was the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks (SVR12) after cessation of HCV therapy.
  
  
  RESULTS
  Among treatment-naive participants, 87 patients (76%) of 114 (95% CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95% CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95% CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95% CI, 73%-99%) and 16 patients (94%) of 17 (95% CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed.
  
  
  CONCLUSIONS
  In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01667731.
authors.affiliation: Viral Hepatitis Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Duke Infectious Diseases, Duke University, Durham, North Carolina.
authors.forename: Susanna
authors.initials: S
authors.lastname: Naggie
authors.affiliation: Clinical Research, Quest Clinical Research, San Francisco, California.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.affiliation: Internal Medicine, Kaiser Permanente, San Francisco, California.
authors.forename: Walford Jeffrey
authors.initials: WJ
authors.lastname: Fessel
authors.affiliation: Philadelphia FIGHT, Philadelphia, Pennsylvania.
authors.forename: Karam
authors.initials: K
authors.lastname: Mounzer
authors.affiliation: Harborview Medical Center, University of Washington, Seattle.
authors.forename: Margaret
authors.initials: M
authors.lastname: Shuhart
authors.affiliation: Division of HIV/AIDS, San Francisco General Hospital, University of California, San Francisco.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Luetkemeyer
authors.affiliation: Internal Medicine, University of California Davis Medical Center in Sacramento.
authors.forename: David
authors.initials: D
authors.lastname: Asmuth
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: Anuj
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: Liyun
authors.initials: L
authors.lastname: Ni
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Fundacion De Investigacion San Juan, Puerto Rico.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.affiliation: Department of Medicine-Liver Diseases, Mount Sinai School of Medicine, New York, New York.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000009:adverse effects / 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