title: How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?
abstract: BACKGROUND
  Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)-HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials.
  
  
  METHODS
  Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOTON-1 (NCT01667731), TURQUOISE-I (NCT01939197), ION-4 (NCT02073656), and ALLY-2 (NCT02032888) that evaluated simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir/dasabuvir; sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir, respectively, to the Canadian Coinfection Cohort, representing approximately 23% of the total coinfected population in care in Canada.
  
  
  RESULTS
  Of 874 active participants, 70% had chronic HCV, of whom 410, 26, 94, and 11 had genotypes 1, 2, 3, and 4, respectively. After applying trial eligibility criteria, only 5.9% (24/410) would have been eligible for enrollment in the simeprevir trial, 9.8% (52/530) in PHOTON-1, 6.3% (26/410) in TURQUOISE-I, and 8.1% (34/421) in ION-4. The ALLY-2 study was more inclusive; 43% (233/541) of the cohort would have been eligible. The most exclusive eligibility criteria across all trials with the exception of ALLY-2 were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%).
  
  
  CONCLUSIONS
  DAA trial results may have limited generalizability, since the majority of coinfected individuals were not eligible to participate. Exclusions appeared to be related to improving treatment outcomes by not including those at higher risk of poor adherence and reinfection--individuals for whom real-world data are urgently needed.
authors.affiliation: Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre.|Department of Epidemiology & Biostatistics.
authors.forename: Sahar
authors.initials: S
authors.lastname: Saeed
authors.affiliation: Department of Epidemiology & Biostatistics.|Department of Economics, McGill University, Montreal, Quebec.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Strumpf
authors.affiliation: Division of Infectious Diseases, Toronto Hospital, University Health Network, Ontario.|Canadian Institutes of Health Research, Canadian HIV Trials Network.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walmsley
authors.affiliation: Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Rollet-Kurhajec
authors.affiliation: Division of Infectious Diseases, Oak Tree Clinic, BC Women's Hospital, Vancouver, British Columbia.
authors.forename: Neora
authors.initials: N
authors.lastname: Pick
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Quebec.
authors.forename: Valerie
authors.initials: V
authors.lastname: Martel-Laferrière
authors.affiliation: Department of Infectious Disease, Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia.
authors.forename: Mark
authors.initials: M
authors.lastname: Hull
authors.affiliation: Southern Alberta HIV Clinic, Calgary.
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.affiliation: Department of Epidemiology & Biostatistics.|Public Health Department, Montreal Health and Social Services Agency, Quebec.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cox
authors.affiliation: Department of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre.|Canadian Institutes of Health Research, Canadian HIV Trials Network.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.forename: Jeff
authors.initials: J
authors.lastname: Cohen
authors.forename: Brian
authors.initials: B
authors.lastname: Conway
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Pierre
authors.initials: P
authors.lastname: Côté
authors.forename: Joseph
authors.initials: J
authors.lastname: Cox
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Shariq
authors.initials: S
authors.lastname: Haider
authors.forename: Marianne
authors.initials: M
authors.lastname: Harris
authors.forename: David
authors.initials: D
authors.lastname: Haase
authors.forename: Mark
authors.initials: M
authors.lastname: Hull
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.forename: Erica
authors.initials: E
authors.lastname: Moodie
authors.forename: Neora
authors.initials: N
authors.lastname: Pick
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Danielle
authors.initials: D
authors.lastname: Rouleau
authors.forename: Roger
authors.initials: R
authors.lastname: Sandre
authors.forename: Joseph Mark
authors.initials: JM
authors.lastname: Tyndall
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Vachon
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.forename: David
authors.initials: D
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000592:standards*; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000998:Antiviral Agents
keywords: HIV–hepatitis C coinfection; clinical trials; direct-acting antivirals; generalizability; people who inject drugs