HIV-1 Tropism Test Evaluation: Assessment and Clinical Implications

CCR5 and CXCR4 chemokines receptors are critical coreceptors for the binding of HIV to specific host cells. Guidelines recommend its assessment in case of virological failure or before prescription of CCR5 inhibitors. Strategies to assess viral tropism may be divided into phenotypic and genotypic assays; registrative trials of CCR5 inhibitors used phenotypic assay, but recently genotypic ones have been used in clinical practice. The presence of CXCR4 is increasing in na？ve patients, with both acute and chronic HIV-1 infections; this coreceptor usage is associated with CD4 depletion. The assessment of viral tropism should be considered in every stage of HIV-1 infection. 1. Introduction HIV enters target cells by interacting with specific surface receptors. While CD4 represents the main molecule with which the HIV envelope is able to interact, several cofactors have been identified. Among those, CCR5 (as discussed by Alkhatib et al. [1]) and CXCR4 (as discussed by Feng et al. [2]) chemokines receptors are critical coreceptors for the binding of HIV to specific host cells. Most HIV-1 quasispecies infect cells expressing CCR5 and are thus defined as CCR5- or R5-tropic, while a smaller proportion of viruses bind to CXCR4 and are defined as CXCR4- or X4-tropic. Moreover, some patients harbour mixed viral populations, and some quasispecies are able to use both coreceptors: those patients are defined as carrying dual/mixed viruses (DM-tropic) (as discussed by Berger et al. [3]). Maraviroc, a CCR5 inhibitor, is the only antiretroviral agent targeting coreceptor binding currently licensed for use in HIV infection. Its use is limited to patients with a determined CCR5 tropism (as discussed elsewhere [4, 5]). Several techniques were developed to assess HIV tropism, and treatment guidelines from different countries are not uniform in defining which methods should be employed in clinical practice. 2. Methods Strategies to assess viral tropism may be divided into two broad categories: phenotypic and genotypic assays. Phenotypic assays determine HIV tropism by culturing host infected cells or by engineering a recombinant virus derived from the virus population of the subject (as discussed by Raymond et al. [6]). Genotypic tests are based on amplification and subsequent sequence analysis of HIV V3 segment by means of prespecified algorithms (as discussed by Obermeier et al. [7]). Among phenotypic assays, Trofile test has been the most widely used (as discussed by Whitcomb et al. [8]), and it has been recently replaced by an equivalent with enhanced sensitivity (Trofile