title: Susceptibility of HIV-1 subtypes B', CRF07_BC and CRF01_AE that are predominantly circulating in China to HIV-1 entry inhibitors.
abstract: BACKGROUND
  The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China.
  
  
  RESULTS
  The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B'), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07_BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B' and CRF01_AE isolates to enfuvirtide. Subtype B' isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07_BC and CRF01_AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 µM exhibited no significant inhibitory activity against any of the isolates tested.
  
  
  CONCLUSIONS
  Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1-infected patients in China.
authors.affiliation: State Key Laboratory for Infection Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention (China-CDC), Beijing, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Weisi
authors.initials: W
authors.lastname: Xu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Fang
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Liying
authors.initials: L
authors.lastname: Ma
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002681:China; D004274:DNA, Recombinant / Q000235:genetics*; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D011110:Polymorphism, Genetic; D016415:Sequence Alignment
chemical_list: D004274:DNA, Recombinant; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors