title: [Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy].
abstract: OBJECTIVE
  To elucidate the molecular evolutional characteristics of HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) drug resistance-associated mutations in patients with AIDS receiving highly active antiretroviral therapy.
  
  
  METHODS
  We selected 4 AIDS patients receiving highly active antiretroviral therapy (HAART) with good adherence under a HIV-1 drug resistance cohort from a rural region in central China. Those people carried susceptible virus at the beginning of treatment and gradually came to produce virus resistant to NRTIs during the process of antiretroviral therapy (ART). Reverse transcriptase (RT) genes from each patient's peripheral blood samples (from 3 to 33 months after withdrawal) were cloned and sequenced in succession.
  
  
  RESULTS
  We sequenced a total number of 855 clones and obtained the HIV-1 NRTI drug resistance-associated mutations patterns of the 4 patients. Typical resistance mutations of thymidine analogue mutations (TAMs) pattern 1, such as L210W, T215Y and M41L, were generated in patient 'A'. TAMs pattern 2, including D67N, K70R and K219Q mutations, was discovered in patient 'B'. Interestingly, in patient 'C', some clones comprising not only TAMs pattern 1 mutations (T215Y) but also TAMs pattern 2 mutations (K70R, D67N).
  
  
  CONCLUSIONS
  The four patients show different pathways on HIV-1 NRTI drug resistance-associated mutations, including TAMs pattern 1, TAMs pattern 2 and the fusion pattern of TAMs-1 & TAMs-2. We also noticed that the tendency of gradual accumulation was obvious and those mutations detected earlier tended to be the predominant strains.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Li
authors.forename: Li-yan
authors.initials: LY
authors.lastname: Jiao
authors.forename: Han-ping
authors.initials: HP
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Yong-jian
authors.initials: YJ
authors.lastname: Liu
authors.forename: Dao-min
authors.initials: DM
authors.lastname: Zhuang
authors.forename: Si-yang
authors.initials: SY
authors.lastname: Liu
authors.forename: Zuo-yi
authors.initials: ZY
authors.lastname: Bao
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Jing-yun
authors.initials: JY
authors.lastname: Li
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors