[Methods for determination of HIV tropism and their clinical use].
Determination of HIV-1 tropism is mandatory before using CCR5 antagonists in clinical practice. One drug of this class, maraviroc, has been approved for the treatment of HIV infection. The phenotypic assay, TrofileTM, was clinically validated in the clinical development program of maraviroc and has been widely used to select candidates for maraviroc therapy. Phenotypic tests, however, have the disadvantage of being complex, are costly and time-consuming, and their accessibility is limited, which hampers their routine use in clinical diagnosis. Genotypic assays, based on sequencing the third hypervariable (V3 loop) of the viral gene env, interpreted according to various genotypic bioinformatic tools, such as geno2pheno and PSSM, are faster and cheaper than phenotypic assays, and are also more accessible. In retrospective analyses of the maraviroc pivotal trials, genotypic methods using either conventional ("bulk") or deep-sequencing technology predicted virologic response to maraviroc similarly to phenotypic assays and are now included within several European recommendations to guide the clinical use of CCR5 antagonists.
Servicio de Enfermedades Infecciosas, Hospital General Universitario de Elche, Alicante, Departamento de Medicina, Universidad Miguel Hernández, Alicante, España. gutierrez_fel@gva.es
Félix
F
Gutiérrez
Juan Carlos
JC
Rodríguez
Federico
F
García
Eva
E
Poveda
D000465:Algorithms; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use; D005060:Europe; D015752:Genes, env; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000077592:Maraviroc; D010446:Peptide Fragments / Q000235:genetics; D010641:Phenotype; D017410:Practice Guidelines as Topic; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D012189:Retrospective Studies; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D056189:Viral Tropism / Q000187:drug effects / Q000235:genetics; D014773:Virology / Q000379:methods*; D053586:Virus Internalization / Q000187:drug effects
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014230:Triazoles; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1; D000077592:Maraviroc