title: Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison.
abstract: OBJECTIVE
  Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV).
  
  
  METHODS
  A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared.
  
  
  RESULTS
  The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL.
  
  
  CONCLUSIONS
  After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts. Electronic address: elyse.swallow@analysisgroup.com.
authors.forename: Elyse
authors.initials: E
authors.lastname: Swallow
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Song
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Anupama
authors.initials: A
authors.lastname: Kalsekar
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kelley
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts.
authors.forename: Miranda
authors.initials: M
authors.lastname: Peeples
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts.
authors.forename: Fan
authors.initials: F
authors.lastname: Mu
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut.
authors.forename: Peter
authors.initials: P
authors.lastname: Ackerman
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Signorovitch
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D002219:Carbamates; D017326:Clinical Trials, Phase III as Topic; D060085:Coinfection; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D011759:Pyrrolidines; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: HIV; daclatasvir; hepatitis C; matching-adjusted indirect comparison; ribavirin; sofosbuvir