title: Natural Polymorphisms Conferring Resistance to HCV Protease and Polymerase Inhibitors in Treatment-Naïve HIV/HCV Co-Infected Patients in China.
abstract: BACKGROUND
  The advent of direct-acting agents (DAAs) has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China.
  
  
  METHODS
  Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1-6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs) were identified in positions associated with HCV resistance.
  
  
  RESULTS
  Overall, 72.8% (566/778) of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193) of genotype 1, 100% (23/23) of genotype 2, 100% (237/237) of genotype 3 and 92% (299/325) of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69) patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance.
  
  
  CONCLUSIONS
  The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed.
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.|University of California San Francisco, Department of Medicine, Division of Gastroenterology, 513 Parnassus Avenue, Room S-357, San Francisco, California, 94143-0538 United States of America.
authors.forename: Kali
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liang
authors.affiliation: UNC-Project - China, Division of Infectious Diseases, Department of Medicine, UNC Chapel Hill School of Medicine, 130 Mason Farm Rd., 2nd Floor, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, 27599-3368, United States of America.|Brown University School of Medicine, Department of Medicine, Division of Gastroenterology 593 Eddy Street, APC 406, Providence, Rhode Island, 02903, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Hu
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.|UNC-Project - China, Division of Infectious Diseases, Department of Medicine, UNC Chapel Hill School of Medicine, 130 Mason Farm Rd., 2nd Floor, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, 27599-3368, United States of America.
authors.forename: Chuanyi
authors.initials: C
authors.lastname: Ning
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Tang
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.|UNC-Project - China, Division of Infectious Diseases, Department of Medicine, UNC Chapel Hill School of Medicine, 130 Mason Farm Rd., 2nd Floor, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, 27599-3368, United States of America.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Tucker
authors.affiliation: Guangzhou Eighth People's Hospital, 627 Dongfeng Dong Road, Guangzhou, Guangdong 510060, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000494:pharmacology*; D002681:China; D060085:Coinfection; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010641:Phenotype; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011480:Protease Inhibitors / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase