title: Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.
abstract: BACKGROUND
  The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1).
  
  
  METHODS
  This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks.
  
  
  RESULTS
  Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised.
  
  
  CONCLUSIONS
  Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).
authors.affiliation: From the University of California, San Diego, La Jolla (D.L.W.), Ruane Medical and Liver Health Institute (P.J.R.), the Jeffrey Goodman Clinic, Los Angeles LGBT Center (C.H.), and Southern California Men's Medical Group-Men's Health Foundation (A.M.), Los Angeles, the University of California, San Francisco, San Francisco (A.L.), Veterans Affairs Long Beach Healthcare System, Long Beach (T.R.M.), and Pacific Oaks Medical Group, Beverly Hills (A.S.) - all in California; Johns Hopkins University, Lutherville, MD (M.S.S.); Icahn School of Medicine at Mount Sinai, New York (D.D.); University of Cincinnati College of Medicine, Cincinnati (K.E.S.); Infectious Disease Specialists of Atlanta, Decatur, GA (R.D.); MedStar Washington Hospital Center (D.F.), Whitman-Walker Health (S.H.), and Capital Medical Associates (B.R.) - all in Washington, DC; the Cure C Consortium, Houston (J.C.G.), and Tarrant County Infectious Disease Associates, Fort Worth (C.M.) - both in Texas; Orlando Immunology Center, Orlando (F.H.), and Midway Immunology and Research Center, Fort Pierce (M.R.) - both in Florida; the University of Alabama at Birmingham, Birmingham (E.T.O.); the University of Colorado, Denver (G.R.); Lehigh Valley Health Network, Allentown, PA (J.Y.); and Bristol-Myers Squibb, Wallingford, CT (F.M., P.D.Y., P.A.), and Princeton, NJ (Z.L., E.H., S.N.).
authors.forename: David L
authors.initials: DL
authors.lastname: Wyles
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ruane
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.forename: Anne
authors.initials: A
authors.lastname: Luetkemeyer
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Robin
authors.initials: R
authors.lastname: Dretler
authors.forename: Dawn
authors.initials: D
authors.lastname: Fishbein
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gathe
authors.forename: Sarah
authors.initials: S
authors.lastname: Henn
authors.forename: Federico
authors.initials: F
authors.lastname: Hinestrosa
authors.forename: Charles
authors.initials: C
authors.lastname: Huynh
authors.forename: Cheryl
authors.initials: C
authors.lastname: McDonald
authors.forename: Anthony
authors.initials: A
authors.lastname: Mills
authors.forename: Edgar Turner
authors.initials: ET
authors.lastname: Overton
authors.forename: Moti
authors.initials: M
authors.lastname: Ramgopal
authors.forename: Bruce
authors.initials: B
authors.lastname: Rashbaum
authors.forename: Graham
authors.initials: G
authors.lastname: Ray
authors.forename: Anthony
authors.initials: A
authors.lastname: Scarsella
authors.forename: Joseph
authors.initials: J
authors.lastname: Yozviak
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
authors.forename: Philip D
authors.initials: PD
authors.lastname: Yin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
authors.forename: Peter
authors.initials: P
authors.lastname: Ackerman
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015497:HIV-1; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; D014542:Uridine Monophosphate; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir