Document Detail


Comparison of population and 454 "deep" sequence analysis for HIV type 1 tropism versus the original trofile assay in non-B subtypes.
MedLine Citation:
PMID:  23350534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV-1 tropism can be predicted using V3 genotypic algorithms. The performance of these prediction algorithms for non-B subtypes is poorly characterized. Here, we use these genotypic algorithms to predict viral tropism of HIV-1 subtype A, B, C, and D to find apparent sensitivity, specificity, and concordance against a recombinant phenotypic assay, the original Trofile assay. This is a substudy of an epidemiological study (Pfizer A4001064). Plasma samples were selected to represent a large number of DM/X4 and R5 viruses. The HIV-1 env gene V3 loop was genotyped by Sanger sequencing (N=260) or 454 "deep" sequencing (N=280). Sequences were scored with g2p[coreceptor], PSSM X4/R5, PSSM SI/NSI, and PSSM subtype C matrices. Overall, non-B subtypes tropism prediction had similar concordance and apparent sensitivity and specificity as subtype B in predicting Trofile's results in both population sequencing (81.3%, 65.6%, and 90.5% versus 84.2%, 78.5%, and 88.2%) and 454 "deep" sequencing (82.3%, 80.0%, and 83.6% versus 86.8%, 92.0%, and 82.6%) using g2p[coreceptor]. By population sequencing, subtype A had lower sensitivity, whereas subtype D had lower specificity for non-R5 predictions, both in comparison to subtype B. 454 "deep" sequencing improved subtype A sensitivity but not subtype D. Subtype C had greater concordance than subtype B regardless of sequencing methods. In conclusion, genotypic tropism prediction algorithms may be applied to non-B HIV-1 subtypes with caution. Collective analysis of non-B subtypes revealed a performance similar to subtype B, whereas a subtype-specific analysis revealed overestimation (subtype D) or underestimation (subtype A).
Authors:
Guinevere Q Lee; P Richard Harrigan; Winnie Dong; Art F Y Poon; Jayvant Heera; James Demarest; Alex Rinehart; Doug Chapman; Hernan Valdez; Simon Portsmouth
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-06
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  29     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-13     Completed Date:  2013-08-30     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  979-84     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Genotype
HIV Envelope Protein gp120 / genetics
HIV-1 / genetics,  physiology*
Peptide Fragments / genetics
Phenotype
Sensitivity and Specificity
Sequence Analysis, DNA / methods
Viral Tropism / genetics*
Grant Support
ID/Acronym/Agency:
201009HOP-235256//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/HIV Envelope Protein gp120; 0/HIV envelope protein gp120 (305-321); 0/Peptide Fragments
Comments/Corrections

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