title: Resistance-associated mutations to HCV protease inhibitors naturally pre-existed in HIV/HCV coinfected, treatment-naïve patients.
abstract: OBJECTIVE
  Presently, it has been approved to treat hepatitis C virus (HCV) infection with protease inhibitors (PIs). In the present study, we aimed to illustrate the natural prevalence of HCV NS3/4A PI resistance mutations in HIV/HCV coinfected, treatment-naïve patients.
  
  
  METHODS
  Population sequence analysis of the NS3/4A protease was conducted in 96 HIV/HCV coinfected, treatment-naïve patients.
  
  
  RESULTS
  Complete HCV NS3/4A sequence information was obtained from 70 (72.92%) samples, including 68 patients (97.14%) with genotype 1b and 2 patients (2.86%) with genotype 2a. A total of 21 patients (30.88%) of the 68 patients with HCV genotype 1b showed amino acid substitutions associated with HCV PI resistance. Mutation F43S was observed in 1.47% of patients with genotype 1b. The mutations of T54S, Q80K/R, R155K, A156G and D168A/E/G were found in 4.41%, 1.47%/1.47%, 2.94%, 23.53% and 1.47%/1.47%/1.47% of patients with genotype 1b, respectively. In addition, 4.41% of patients with genotype 1b showed double mutations in the NS3 region. The multiple mutations of Q80R+R155K+D168G and Q80K+R155K+A156G+D168A were detected in 1.47% and 1.47% of patients with HCV genotype 1b, respectively.
  
  
  CONCLUSIONS
  The most predominant HCV genotype was 1b in patients with HIV/HCV coinfection. Naturally occurring mutations resistant to HCV PIs (simeprevir, vaniprevir, boceprevir, telaprevir, asunaprevir and paritaprevir) pre-existed in patients with HIV/HCV genotype 1b coinfection. The effects of baseline PI resistance on treatment outcome should be further analyzed.
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China; Department of Neurology, Shiyan Taihe Hospital, Shiyan, Hubei Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
authors.forename: Feili
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China.
authors.forename: Renwen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China. Electronic address: xiaoyuanxu6@163.com.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Xu
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D060085:Coinfection; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011480:Protease Inhibitors / Q000627:therapeutic use*
chemical_list: D011480:Protease Inhibitors