Clinical trial NCT01381328: GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
Official title: GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: HIV-1 Infected Patients
Fold-change Resistance
Resistance Mutations
Keywords: HIV-1 infected patients
RALTEGRAVIR regimen
genotypic evaluations
phenotypic evaluations
Lead sponsor: Università Vita-Salute San Raffaele
Sponsor class: OTHER
Collaborators: name: IRCCS San Raffaele
name: Merck Sharp & Dohme LLC
First posted: 2011-06-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: primary care clinic

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: - mean value of fold-change resistance determined by the phenotypic assay at baseline
timeFrame: baseline
Secondary outcomes:
measure: changes of fold-change resistance determined by the phenotypic assay with respect to baseline.
timeFrame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
measure: genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations)
timeFrame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
measure: changes of the replication capacity with respect to baseline
timeFrame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
measure: changes of HIV-RNA with respect to baseline
timeFrame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
measure: changes in CD4, CD4%, CD8, CD8% with respect to baseline
timeFrame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Department of Infectious Diseases, IRCCS San Raffaele Hospital
Study officials:
affiliation: University Vita-Salute San Raffaele Laboratory of Microbiology and Virology
name: Massimo Clementi, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, IRCCS San Raffaele Hospital
name: Antonella Castagna, MD
role: STUDY_DIRECTOR
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