Assessment of HIV-1 tropism using genotypic approaches

2012 | Hot Topics in HIV and other Retroviruses: Issue 3

Program(s): Laboratory |

Hot Topics in HIV and other Retroviruses

Abstract:

Human immunodeficiency virus-1 (HIV-1) infects cells by binding onto cell-surface CD4 molecules and coreceptors such as CC chemokine receptor type 5 (CCR5) or CXC chemokine receptor type 4 (CXCR4); HIV-1 tropismrefers to the virus’ coreceptor preference. CCR5-antagonists are a class of clinically approved HIV cell-entry inhibitors effective only against variants that use CCR5; thus requiring a viral tropism screen before use. Currently, treatment guidelines from the United States recommend a phenotypic (infection-assay-based) screening method called Enhanced Sensitivity Trofile Assay (ESTA), whereas Canadian and European treatment guidelines recommend genotypic (sequencing-assay-based) screening of viral tropism. This review provides background information on HIV-1 tropism and methods of its determination, with a focus on genotypic methods. Different genotypic tropism interpretation algorithms (including geno2pheno_[coreceptor], position-specific scoring matrices [PSSMs], and Wetcat) and two types of sequencing technologies (Sanger and “deep” sequencing) are described. Finally, studies on concordance between these methods against phenotypic methods and clinical outcome are summarized. Overall, genotypic HIV tropism prediction methods have been validated as clinically useful and are gaining popularity worldwide.

BC Centre for Excellence in HIV/AIDS

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Assessment of HIV-1 tropism using genotypic approaches

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