Comparison of two genotypic algorithms to determine HIV-1 tropism.
OBJECTIVE
One or both of two co-receptors, CCR5 (R5) and CXCR4 (X4), are used by HIV-1 to enter into host cells. The glycoprotein 120 (gp120) V3 sequence is correlated with the R5 and X4 phenotype. CCR5 inhibitors are specifically active against R5 viruses, suggesting the need to determine tropism before the use of these antagonists. A comparison of the position-specific scoring matrices (PSSM) and Geno2pheno algorithms based on the V3 loop gp120 sequences and previously described to be correlated to the R5 or X4 phenotype was carried out.


METHODS
V3 envelope (env) genes from 83 plasma samples were amplified and sequenced, and 69 sequences were analysed with the PSSM and Geno2pheno algorithms.


RESULTS
These two algorithms were concordant in 86.5% of cases. The Geno2pheno algorithm gave a tropism result more frequently than the PSSM algorithm, but R5X4 or X4 viruses were less frequently detected by the Geno2pheno algorithm. R5X4 or X4 tropism was predicted in 29.9% of samples. There was more R5X4 co-receptor use in the antiretroviral-treated group than in the antiretroviral-naïve group.


CONCLUSIONS
It is advisable to run a validated co-receptor use prediction tool before using co-receptor antagonists. If genotyping methods are considered, the PSSM and Geno2pheno algorithms are complementary and both are necessary. The association between predicted co-receptor use and virological response to co-receptor antagonists needs to be thoroughly evaluated.
Soulié
C
C
Department of Virology, Pitié Salpêtrière Hospital, Pierre et Marie Curie-Paris 6 University, 47-83 Bd de l'Hôpital, 75651 Paris Cedex 13, France. cathia.soulie@psl.aphp.fr
Derache
A
A
Aimé
C
C
Marcelin
A-G
AG
Carcelain
G
G
Simon
A
A
Katlama
C
C
Calvez
V
V
D000328:Adult; D000368:Aged; D000465:Algorithms; D018791:CD4 Lymphocyte Count / Q000379:methods; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D019713:Receptors, CCR5 / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018523:Tropism; D019562:Viral Load
D019713:Receptors, CCR5; D019718:Receptors, CXCR4