Performance of a population-based HIV-1 tropism phenotypic assay and correlation with V3 genotypic prediction tools in recent HIV-1 seroconverters.
BACKGROUND
Pure X4 and X4R5 dual-tropic viruses may be recognized in approximately 15% of drug-naive HIV-1-positive patients. CCR5 antagonists are active against R5 viruses; therefore, HIV tropism should be known before their prescription.


METHODS
A population-based phenotypic assay was performed in 61 recent HIV-1 seroconverters. The results were compared with those obtained using 8 different predictor software programs (C4.5, C4.5 with 8 and 12, PART, SVM, Charge Rule, PSSMsinsi, PSSMx4r5, and geno2pheno), which are freely available at 3 different Web sites and use V3 sequences derived from patient's viruses.


RESULTS
Phenotypic testing reported X4R5 dual-tropic viruses in 10 (16.4%) patients. CD4 cell counts and viral loads were significantly lower in X4R5 dual-tropic (450 cells/microL and 3.9 log HIV RNA copies/mL) than in R5 viruses (629 cells/microL, 4.5 log HIV RNA copies/mL) (P<0.05). The overall concordance of genotype and phenotype was relatively good (>80%). Although specificity was >90% using all but 1 genotypic predictor (geno2pheno), however, the sensitivity for the detection of X4 variants was low (<30%), except for SVM and geno2pheno (70%).


CONCLUSIONS
The prevalence of X4 and X4/R5 dual-tropic viruses in recent HIV seroconverters is 16%. Current genotypic algorithms need to be improved for the estimation of HIV-1 coreceptor use before moving to the clinic. This information is crucial for the selection of candidates to receive CCR5 antagonists in places where phenotypic tropism assays may not be feasible.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. cmendoza@teleline.es
Carmen
C
de Mendoza
Kurt
K
Van Baelen
Eva
E
Poveda
Evelien
E
Rondelez
Natalia
N
Zahonero
Lieven
L
Stuyver
Carolina
C
Garrido
Jorge
J
Villacian
Vincent
V
Soriano
D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D005814:Genes, Viral; D005821:Genetic Techniques; D005838:Genotype; D006679:HIV Seropositivity / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D012680:Sensitivity and Specificity; D018523:Tropism; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load
D014759:Viral Envelope Proteins