title: Distinctive Drug-resistant Mutation Profiles and Interpretations of HIV-1 Proviral DNA Revealed by Deep Sequencing in Reverse Transcriptase.
abstract: OBJECTIVE
  To investigate distinctive features in drug-resistant mutations (DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients.
  
  
  METHODS
  Forty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA.
  
  
  RESULTS
  Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher's exact test, P<0.05). Considering 'majority resistant variants', 15 samples (19.48%) showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering 'minority resistant variants', 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA.
  
  
  CONCLUSIONS
  Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China; State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Zhen Peng
authors.initials: ZP
authors.lastname: Li
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Wei Si
authors.initials: WS
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Key Laboratory of Medical Molecular Virology (Ministries of Education and Health), Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200433, China.
authors.forename: Shi Bo
authors.initials: SB
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Yi Ming
authors.initials: YM
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Ma
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D002681:China; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011533:Proviruses / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase
keywords: Deep sequencing; Drug-resistance interpretation; HIV-1 drug-resistant mutation; Proviral DNA; Viral RNA