MAIN APPLICATIONS

• Determination of viral tropism
  Before starting treatment with antagonist of CCR5 a tropism test should be performed in every patient. The recombinant viruses covered by this patent can be used to perform that task at a reasonable price.
• Titration of neutralizing antibodies
  -Our results are highly concordant with those of the laboratories and methodologies considered the gold standards in the field.
  -Different panels of HIV strains that cover the spectrum of viruses that should be neutralized by an effective vaccine have been developed.
• Evaluation of new antivirals
  -The system has many advantages as compared to other current tests (biological test, low costs and time, sensitivity, versatility…).
  -A broad collection of recombinant viruses generated in the laboratory allows full characterization of the antiviral activity of a given compound.
• Phenotypic resistance to antiretroviral drugs
  A collection of viral clones carrying different mutations of resistance has been generated. This panel of resistant viruses remains a major tool to analyze cross-resistance of new antiretroviral drugs.

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1. Determination of viral tropism: According to regulatory authority (FDA, EMA) only patients displaying an R5 phenotype should be treated with CCR5 inhibitors. Genotypic testing and predictive algorithms have many limitations, however, our recombinant viruses can be used to perform the test solving these problems. Our test increases sensitivity in the detection of minority variants and lacks of algorithms for interpretation that can biased results. This tropism test has been validated with the TROFILE^TM

2. Titration of neutralizing antibodies: The development of new vaccine prototypes aiming at the induction of neutralizing antibodies has increased the utility of this application. Our laboratory has participated in this validation and our results are highly concordant with the laboratories and methodologies that are considered as the gold standards in the field. We have developed different panels of HIV strains that cover the spectrum of viruses that should be neutralized by an effective vaccine.

3. Activity of new antivirals and phenotypic resistance to antiretroviral drugs: The system has many advantages as compared to other current tests (biological test, low costs and time, sensitivity, versatility…). For new drugs it is important to check its activity against resistant viruses to other drugs of the same family. In this context, we have generated along these years a broad collection of viral clones carrying different mutations of resistance to non-nucleoside reverse transcriptase inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, integrase inhibitors and Maraviroc. The large collection of recombinant viral clones and specific techniques have been set up to fully characterize the mechanism of action of a given compound displaying antiviral activities: viral entry, fusion, retrotranscription, integration, transcription and viral morphogenesis and infectivity.