title: Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.
abstract: BACKGROUND
  Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.
  
  
  METHODS
  We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
  
  
  RESULTS
  Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.
  
  
  CONCLUSIONS
  Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (S.N.); University of Ottawa, the Ottawa Hospital, Ottawa (C.C.), and Department of Hepatology, Immunodeficiency Clinic, Toronto General Hospital, University of Toronto, Toronto (D.K.W.) - both in Canada; University of Alabama at Birmingham, Birmingham (M. Saag); Emory University, Emory Healthcare, Atlanta (K.W.); Ruane Medical and Liver Health Institute (P.R.) and Kaiser Permanente Los Angeles Medical Center (W.J.T.), Los Angeles, University of California, San Francisco, San Francisco General Hospital, San Francisco (A.L.), and Gilead Sciences, Foster City (L.M.S., J.C.Y., P.G., H.D.-S., L.N., P.S.P., J.G.M.) - all in California; Weill Cornell Medical College (K.M.), Icahn School of Medicine at Mount Sinai (N.B., D.D.), New York, and James J. Peters Veterans Affairs Medical Center, Bronx (N.B.) - all in New York; Beth Israel Deaconess Medical Center (R.P.B.), Brigham and Women's Hospital and Harvard Medical School (P.E.S.), and Community Research Initiative of New England (A.E.C.) - all in Boston; University of Auckland, Auckland City Hospital, Auckland (E.G.), and Christchurch Hospital and University of Otago, Christchurch (C.A.M.S.) - both in New Zealand; University of Puerto Rico School of Medicine (J.S.-B.) and Clinical Research Puerto Rico (J.O.M.-R.) - both in San Juan; University of Miami, Miami (D.J.); University of Pennsylvania, Philadelphia (P.T.); and Johns Hopkins University School of Medicine, Baltimore (M. Sulkowski).
authors.forename: Susanna
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authors.lastname: Naggie
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Michael
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authors.lastname: Saag
authors.forename: Kimberly
authors.initials: K
authors.lastname: Workowski
authors.forename: Peter
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authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Kristen
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authors.lastname: Marks
authors.forename: Anne
authors.initials: A
authors.lastname: Luetkemeyer
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Baden
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authors.initials: PE
authors.lastname: Sax
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: Jorge
authors.initials: J
authors.lastname: Santana-Bagur
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Stamm
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Yang
authors.forename: Polina
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authors.lastname: German
authors.forename: Hadas
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authors.lastname: Dvory-Sobol
authors.forename: Liyun
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authors.lastname: Ni
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Catherine A M
authors.initials: CA
authors.lastname: Stedman
authors.forename: Javier O
authors.initials: JO
authors.lastname: Morales-Ramirez
authors.forename: Norbert
authors.initials: N
authors.lastname: Bräu
authors.forename: Dushyantha
authors.initials: D
authors.lastname: Jayaweera
authors.forename: Amy E
authors.initials: AE
authors.lastname: Colson
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: David K
authors.initials: DK
authors.lastname: Wong
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; 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; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D014542:Uridine Monophosphate; D000069474:Sofosbuvir