title: Mutation covariation of HIV-1 CRF07_BC reverse transcriptase during antiretroviral therapy.
abstract: OBJECTIVE
  To understand the effect of HIV-1 drug resistance mutations in the context of antiretroviral therapy (ART), we compared the prevalence of protease (PR) and reverse transcriptase (RT) mutations in HIV-1 CRF07_BC sequences from blood samples of treatment-naive and ART-treated patients.
  
  
  METHODS
  Mutation covariation in the RT and PR of HIV-1 CRF07_BC viruses from 542 treatment-naive patients and 261 patients treated with lamivudine/zidovudine/nevirapine or lamivudine/zidovudine/efavirenz was analysed. Stratified networks were used to display the mutation covariation.
  
  
  RESULTS
  Based on the comparison between treatment-naive and ART-treated patients, three types of featured mutations for RT and PR were initially identified: treatment-associated mutations, treatment-agonistic mutations and overlapping polymorphisms. Twelve significant covariation pairs were found between five treatment-associated mutations (K103N, M184V, Q197K, G190A and Y181C) and nine overlapping polymorphisms (A36E, D39N, Y121H, D123E, R135I, T200A, R277K, L283I and D291E). Meanwhile, three covariation pairs between three treatment-associated mutations (I132L and M184V for RT and I15V for PR) and three overlapping polymorphisms (L10I, L36M and A71V) for PR were also detected. Finally, the overlapping polymorphisms for RT and PR were both found to have significant correlations with treatment-associated mutations, indicating a possible association between polymorphisms and drug resistance. When compared with HIV-1 subtype B under the same regimens as CRF07_BC, the mutation covariations of CRF07_BC showed a distinct pattern of RT and PR mutation covariation.
  
  
  CONCLUSIONS
  The role of polymorphisms in the development of drug resistance has been widely reported. Here, we found a significant correlation between overlapping polymorphisms for RT and PR and treatment-associated mutations, indicating that polymorphisms exert a global influence on treatment-associated mutations. Polymorphism mutations might therefore be considered before initiating ART to improve the efficacy of drug combinations.
authors.affiliation: State Key Laboratory for 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 (China-CDC), Beijing 102206, China.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Yabo
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.forename: Lingjie
authors.initials: L
authors.lastname: Liao
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.forename: Liying
authors.initials: L
authors.lastname: Ma
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense
chemical_list: D044966:Anti-Retroviral Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease
keywords: ART; RT; drug resistance