GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance

• changes of fold-change resistance determined by the phenotypic assay with respect to baseline. [ Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation ] [ Designated as safety issue: No ]
• genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations) [ Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation. ] [ Designated as safety issue: No ]
• changes of the replication capacity with respect to baseline [ Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation. ] [ Designated as safety issue: No ]
• changes of HIV-RNA with respect to baseline [ Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation ] [ Designated as safety issue: No ]
• changes in CD4, CD4%, CD8, CD8% with respect to baseline [ Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation ] [ Designated as safety issue: No ]

The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay.

The secondary objectives are, as follows:

• to establish standardised genotypic assay for the HIV-1 pol gene region (region of interest, sensitivity, mutations involved as primary or compensatory changes, role of polymorphism present at baseline).
• to reach consensus on the algorithm interpretation of in house ex-vivo genotypic evaluations.
• to assess the genetic changes in RAL-failing patients under continuous drug pressure or drug discontinuation (dynamics of the reversion of resistance mutations).
• to evaluate in RAL resistant HIV-1 variants the changes in replication capacity (RC) (baseline vs. following-timepoints).
• to evaluate the immunological and virological trend associated with a raltegravir-regimen failure.

primary care clinic

• HIV-1 Infected Patients
• Fold-change Resistance
• Resistance Mutations

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Inclusion Criteria:

• Adult (at least 18 years of age) treatment-experienced, HIV-infected subjects of either sex and of any race, failing to a RAL-containing regimen will be enrolled in the study

Exclusion Criteria:

• none

• IRCCS San Raffaele
• Merck