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. PATIENTS AND 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.
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. PATIENTS AND 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.
Authors: A Gonzalez-Serna; R A McGovern; P R Harrigan; F Vidal; A F Y Poon; S Ferrando-Martinez; M A Abad; M Genebat; M Leal; E Ruiz-Mateos Journal: Antimicrob Agents Chemother Date: 2011-12-05 Impact factor: 5.191
Authors: S G Parisi; C Andreoni; L Sarmati; C Boldrin; A R Buonomini; S Andreis; R Scaggiante; M Cruciani; O Bosco; V Manfrin; G d'Ettorre; C Mengoli; V Vullo; G Palù; M Andreoni Journal: J Clin Microbiol Date: 2011-03-02 Impact factor: 5.948
Authors: Iris Chen; Wei Huang; Matthew B Connor; Arne Frantzell; Vanessa Cummings; Geetha G Beauchamp; Sam Griffith; Sheldon D Fields; Hyman M Scott; Steven Shoptaw; Carlos Del Rio; Manya Magnus; Sharon Mannheimer; Hong-Van Tieu; Darrell P Wheeler; Kenneth H Mayer; Beryl A Koblin; Susan H Eshleman Journal: HIV Clin Trials Date: 2016-06-14
Authors: S Baroncelli; C M Galluzzo; M Andreotti; M F Pirillo; V Fragola; L E Weimer; M Giuliano; S Vella; L Palmisano Journal: Eur J Clin Microbiol Infect Dis Date: 2013-07-04 Impact factor: 3.267
Authors: Jan Weber; Ana C Vazquez; Dane Winner; Richard M Gibson; Ariel M Rhea; Justine D Rose; Doug Wylie; Kenneth Henry; Alison Wright; Kevin King; John Archer; Eva Poveda; Vicente Soriano; David L Robertson; Paul D Olivo; Eric J Arts; Miguel E Quiñones-Mateu Journal: J Clin Microbiol Date: 2013-03-13 Impact factor: 5.948