Purpose of review: 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.
Recent findings: 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.
Summary: 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.