HIV Coreceptor Phenotyping in the Clinical Setting

The introduction of CCR5 antagonists increases the options available for constructing antiretroviralregimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptortropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usageincreases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression andincreasing their risk for developing antiretroviral resistance. This review discusses current and futuremethods of determining HIV tropism, with a focus on their utility in the clinical setting for screeningpurposes. Some of these methods include recombinant phenotypic tests, such as the MonogramTrofile™ assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometrybased methods. Currently, the best evidence supports the use of phenotypic methods, although othermethods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists mayreduce costs and increase turnaround time over phenotypic methods. The presence of low levels ofX4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derivedsamples when compared to clonally derived samples. Gaining a better understanding of the outputof these assays and correlating them with clinical progression and therapy response will provide someindication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usagecan be improved. In addition, leveraging new technologies capable of detecting low-level minorityspecies may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.