title: Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.
abstract: BACKGROUND
  The human immunodeficiency virus 1 (HIV-1) epidemic in China historically stemmed from intravenous drug users (IDUs) in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV)/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.
  
  
  METHODS
  Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.
  
  
  RESULTS
  Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293), 3a (21.8%, 64/293), 6n (14.0%, 41/293), 1b (10.6%, 31/293), 1a (8.2%, 24/293), 6a (5.1%, 15/293) and 6u (2.4%, 7/293). The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong) and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan) bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1) and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6), suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A) to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs)-naïve IDUs.
  
  
  CONCLUSIONS
  This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and evolution of HCV in IDUs and are valuable for developing HCV prevention and management strategies for this population.
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Luo
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Mei
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Dong
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.
authors.forename: Manhong
authors.initials: M
authors.lastname: Jia
authors.affiliation: Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, 650022, China.|College of Public Health, Kunming Medical University, Kunming, Yunnan, 650500, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000328:Adult; D002681:China / Q000453:epidemiology; D060085:Coinfection / Q000453:epidemiology / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics; D058872:Epidemics; D005260:Female; D005838:Genotype; D005843:Geography; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000453:epidemiology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D015995:Prevalence; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D014759:Viral Envelope Proteins / Q000145:classification / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000145:classification / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase