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HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays

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Abstract
Background: HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal treatment options, massively parallel sequencing of the envelope V3 domain, in combination with tropism prediction tools, was evaluated as an alternative tropism determination strategy. Plasma samples from twelve HIV-1 infected individuals with failing phenotyping results were available. The samples were submitted to massive parallel sequencing and to confirmatory recombinant phenotyping using a fraction of the gp120 domain. Results: A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly. Conclusions: Although only demonstrated on a limited set of samples, the potential of the combined use of “deep sequencing + prediction algorithms” in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development.

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Chicago
Vandenbroucke, Ina, Herwig Van Marck, Wendy Mostmans, Veerle Van Eygen, Evelien Rondelez  , Kim Thys  , Kurt Van Baelen  , et al. 2010. “HIV-1 V3 Envelope Deep Sequencing for Clinical Plasma Specimens Failing in Phenotypic Tropism Assays.” Aids Research and Therapy 7.
APA
Vandenbroucke, I., Van Marck, H., Mostmans, W., Van Eygen, V., Rondelez  , E., Thys  , K., Van Baelen  , K., et al. (2010). HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays. AIDS RESEARCH AND THERAPY, 7.
Vancouver
1.
Vandenbroucke I, Van Marck H, Mostmans W, Van Eygen V, Rondelez  E, Thys  K, et al. HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays. AIDS RESEARCH AND THERAPY. 2010;7.
MLA
Vandenbroucke, Ina, Herwig Van Marck, Wendy Mostmans, et al. “HIV-1 V3 Envelope Deep Sequencing for Clinical Plasma Specimens Failing in Phenotypic Tropism Assays.” AIDS RESEARCH AND THERAPY 7 (2010): n. pag. Print.
@article{1233638,
  abstract     = {Background: HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal treatment options, massively parallel sequencing of the envelope V3 domain, in combination with tropism prediction tools, was evaluated as an alternative tropism determination strategy. Plasma samples from twelve HIV-1 infected individuals with failing phenotyping results were available. The samples were submitted to massive parallel sequencing and to confirmatory recombinant phenotyping using a fraction of the gp120 domain.
Results: A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly.
Conclusions: Although only demonstrated on a limited set of samples, the potential of the combined use of “deep sequencing + prediction algorithms” in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development.},
  articleno    = {4},
  author       = {Vandenbroucke, Ina and Van Marck, Herwig and Mostmans, Wendy and Van Eygen, Veerle and Rondelez  , Evelien and Thys  , Kim and Van Baelen  , Kurt and Fransen, Katrien and Vaira, Dolores and Kabeya, Kabamba  and De Wit , Stephane and Florence  , Eric and Moutschen   , Michel and Vandekerckhove, Linos and Verhofstede, Chris and Stuyver, Lieven J},
  issn         = {1742-6405},
  journal      = {AIDS RESEARCH AND THERAPY},
  language     = {eng},
  pages        = {6},
  title        = {HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays},
  url          = {http://dx.doi.org/10.1186/1742-6405-7-4},
  volume       = {7},
  year         = {2010},
}

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