title: Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial.
abstract: OBJECTIVE
  Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake.
  
  
  OBJECTIVE
  To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis.
  
  
  METHODS
  TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen.
  
  
  METHODS
  Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized.
  
  
  METHODS
  The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12).
  
  
  RESULTS
  Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment.
  
  
  CONCLUSIONS
  In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01939197.
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: University of North Carolina, Chapel Hill.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.affiliation: University of California, San Diego, La Jolla.
authors.forename: David
authors.initials: D
authors.lastname: Wyles
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Roger
authors.initials: R
authors.lastname: Trinh
authors.affiliation: Quest Clinical Research, San Francisco, California.
authors.forename: Jay
authors.initials: J
authors.lastname: Lalezari
authors.affiliation: Virginia Mason Medical Center, Seattle, Washington.
authors.forename: Chia
authors.initials: C
authors.lastname: Wang
authors.affiliation: St Michael's Medical Center, Newark, New Jersey.
authors.forename: Jihad
authors.initials: J
authors.lastname: Slim
authors.affiliation: AIDS Healthcare Foundation, Beverly Hills, California.
authors.forename: Laveeza
authors.initials: L
authors.lastname: Bhatti
authors.affiliation: Cure C. Consortium, Houston, Texas.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.affiliation: Ruane Medical and Liver Health Institute, Los Angeles, California.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ruane
authors.affiliation: Whitman-Walker Health, Washington, DC.
authors.forename: Richard
authors.initials: R
authors.lastname: Elion
authors.affiliation: Metropolis Medical Group, San Francisco, California.
authors.forename: Fritz
authors.initials: F
authors.lastname: Bredeek
authors.affiliation: Infectious Diseases Associates of Central Virginia, Lynchburg.
authors.forename: Robert
authors.initials: R
authors.lastname: Brennan
authors.affiliation: Circle Care Center, Norwalk, Connecticut.
authors.forename: Gary
authors.initials: G
authors.lastname: Blick
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Amit
authors.initials: A
authors.lastname: Khatri
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Krystal
authors.initials: K
authors.lastname: Gibbons
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Yiran B
authors.initials: YB
authors.lastname: Hu
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Linda
authors.initials: L
authors.lastname: Fredrick
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Gretja
authors.initials: G
authors.lastname: Schnell
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Tami
authors.initials: T
authors.lastname: Pilot-Matias
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Barbara
authors.initials: B
authors.lastname: Da Silva-Tillmann
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Barbara
authors.initials: B
authors.lastname: McGovern
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Campbell
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
mesh_terms: D015081:2-Naphthylamine; D000328:Adult; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D060085:Coinfection; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011392:Proline / Q000031:analogs & derivatives; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir