| Abstract: | The clinical application of CCR5 antagonists involves first determiningthe coreceptor usage by the infecting viral strain. Bioinformatics programs thatpredict coreceptor usage could provide an alternative method to screen candidates fortreatment with CCR5 antagonists, particularly in countries with limited financialresources. Thus, the present study aims to identify the best approach usingbioinformatics tools for determining HIV-1 coreceptor usage in clinical practice.Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects underclinical monitoring were analyzed in this study. Based on the Trofile results, theviral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination oftropism using a Geno2pheno[coreceptor] analysis with a false positive rateof 10% gave the most suitable performance in this sampling: the R5 and X4 strainswere found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6%concordance between the phenotypic and genotypic results. Further studies are neededto clarify how genetic diversity amongst virus strains affects bioinformatics-drivenapproaches for determining tropism. Although this strategy could be useful forscreening patients in developing countries, some limitations remain that restrict thewider application of coreceptor usage tests in clinical practice. |
