HIV coreceptor phenotyping in the clinical setting.
The introduction of CCR5 antagonists increases the options available for constructing antiretroviral regimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptor tropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage increases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression and increasing their risk for developing antiretroviral resistance. This review discusses current and future methods of determining HIV tropism, with a focus on their utility in the clinical setting for screening purposes. Some of these methods include recombinant phenotypic tests, such as the Monogram Trofile assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometry based methods. Currently, the best evidence supports the use of phenotypic methods, although other methods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce costs and increase turnaround time over phenotypic methods. The presence of low levels of X4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derived samples when compared to clonally derived samples. Gaining a better understanding of the output of these assays and correlating them with clinical progression and therapy response will provide some indication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usage can be improved. In addition, leveraging new technologies capable of detecting low-level minority species may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.
Low
Andrew J
AJ
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Swenson
Luke C
LC
Harrigan
P Richard
PR
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D010641:Phenotype; D011933:Reagent Kits, Diagnostic; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011995:Recombination, Genetic
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015699:HIV Envelope Protein gp120; D011933:Reagent Kits, Diagnostic; D019713:Receptors, CCR5; D019718:Receptors, CXCR4