Comparison of population and 454 "deep" sequence analysis for HIV type 1 tropism versus the original trofile assay in non-B subtypes.
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).
BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
Guinevere Q
GQ
Lee
P Richard
PR
Harrigan
Winnie
W
Dong
Art F Y
AF
Poon
Jayvant
J
Heera
James
J
Demarest
Alex
A
Rinehart
Doug
D
Chapman
Hernan
H
Valdez
Simon
S
Portsmouth
D000465:Algorithms; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics; D010641:Phenotype; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods; D056189:Viral Tropism / Q000235:genetics*
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments