title: Determination of viral tropism by genotyping and phenotyping assays in Brazilian HIV-1-infected patients.
abstract: The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were 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 needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.
authors: Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors: Liã Bárbara
authors: LB
authors: Arruda
authors: Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology School of Medicine at University of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors: Marilia Ladeira de
authors: ML
authors: Araújo
authors: Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology School of Medicine at University of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors: Maira Luccia
authors: ML
authors: Martinez
authors: HIV Out-clinic, Ambulatory of Secondary Immunodeficiencies, ADEE3002, Department of Dermatology, Hospital of Clinics at School of Medicine, University of São Paulo.
authors: Claudio Roberto
authors: CR
authors: Gonsalez
authors: Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology School of Medicine at University of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors: Alberto José da Silva
authors: AJ
authors: Duarte
authors: Monogram Biosciences, Inc., South San Francisco, CA, USA.
authors: Eoin
authors: E
authors: Coakley
authors: Monogram Biosciences, Inc., South San Francisco, CA, USA.
authors: Yolanda
authors: Y
authors: Lie
authors: Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors: Jorge
authors: J
authors: Casseb
mesh_terms: D001938:Brazil; D065100:CCR5 Receptor Antagonists; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D010641:Phenotype; D056189:Viral Tropism / Q000235:genetics*
chemical_list: D065100:CCR5 Receptor Antagonists