Phenotyping methods for determining HIV tropism and applications in clinical settings

Abstract

HIV-1 enters CD4-expressing cells via one or both of the chemokine receptors CCR5 and CXCR4. Specific CCR5 antagonists are now in clinical use, but only for CCR5-tropic viruses. Hence, several methods have been developed for assessing HIV-1 tropism in patients who are candidates for CCR5 antagonists. This article reviews current data on phenotypic assays of tropism. Phenotypic assays are still used as reference, although genotypic methods have improved. The main advantages of phenotypic assays are their great sensitivity for detecting minor CXCR4-using variants and their capacity to assess non-B subtypes of HIV-1. Clinical trials of maraviroc have, thus, relied on the phenotypic determination of HIV-1 tropism. However, new genotypic approaches that are more sensitive for minor CXCR4-using variants, notably ultra-deep pyrosequencing, are now challenging phenotypic assays. Nevertheless, phenotypic assays are essential for improving genotypic algorithms for determining HIV-1 tropism as well as for assessing the resistance of R5-tropic viruses to CCR5 antagonists. HIV-1 tropism should be determined before using CCR5 antagonists. Phenotypic recombinant assays are still the benchmark tests for characterizing HIV-1 tropism as their great sensitivity enables them to detect minor CXCR4-using variants of both B and non-B HIV-1 subtypes.