title: Sofosbuvir for chronic hepatitis C virus infection genotype 1-4 in patients coinfected with HIV.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality among HIV-infected patients. Sofosbuvir is a first-in-class HCV NS5B inhibitor with potent pan-genotypic antiviral activity. We report a 2-part study that assessed the efficacy and safety of sofosbuvir in HCV/HIV-coinfected patients. Part A examined potential drug interactions between sofosbuvir and antiretrovirals (efavirenz, emtricitabine, tenofovir, zidovudine, lamivudine, atazanavir, ritonavir, darunavir, and raltegravir). Part B was a pilot study of sofosbuvir plus peginterferon-ribavirin administered for 12 weeks.
  
  
  METHODS
  We enrolled noncirrhotic patients with chronic HCV infection (genotype, 1-6) and stable HIV. Part A followed a 5-cohort, open-label, multiple-dose, single-sequence design; part B followed an open-label, single-arm design. The primary end point of part B was sustained virologic response (defined as undetectable HCV RNA) 12 weeks after end of treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT01565889.
  
  
  RESULTS
  Thirty-eight patients were enrolled in part A and 23 in part B. In part A, no clinically significant drug interactions were observed between sofosbuvir and any of the antiretrovirals evaluated. In part B, 21 (91.3%) patients achieved SVR12. Two patients relapsed but none experienced on-treatment HCV virologic failure. Two patients discontinued study treatment because of adverse events (altered mood and anemia). No serious adverse events, HIV viral breakthrough, or decreases in CD4 percentage were reported in either part A or part B.
  
  
  CONCLUSIONS
  Sofosbuvir may be coadministered safely with many commonly used antiretrovirals. The addition of sofosbuvir to peginterferon-ribavirin was highly effective as assessed by SVR in HCV/HIV-coinfected patients.
authors.affiliation: *Fundacion de Investigacion, Santurce, Puerto Rico; †Gilead Sciences, Inc, Foster City, CA; and ‡University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Anuj
authors.initials: A
authors.lastname: Gaggar
authors.forename: Gong
authors.initials: G
authors.lastname: Shen
authors.forename: Brian
authors.initials: B
authors.lastname: Kirby
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.forename: Diana
authors.initials: D
authors.lastname: Brainard
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Milagros
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez-Orengo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; 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
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir