Evaluation of the Genotypic Prediction of HIV-1 Coreceptor Use versus a Phenotypic Assay and Correlation with the Virological Response to Maraviroc: the ANRS GenoTropism Study
Open Access
- 1 August 2010
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 54 (8), 3335-3340
- https://doi.org/10.1128/aac.00148-10
Abstract
Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.Keywords
This publication has 18 references indexed in Scilit:
- Development and performance of a new recombinant virus phenotypic entry assay to determine HIV-1 coreceptor usageJournal of Clinical Virology, 2010
- Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropismAIDS, 2008
- Antiretroviral Drug Resistance Testing in Adult HIV‐1 Infection: 2008 Recommendations of an International AIDS Society–USA PanelClinical Infectious Diseases, 2008
- Evaluation of Eight Different Bioinformatics Tools To Predict Viral Tropism in Different Human Immunodeficiency Virus Type 1 SubtypesJournal of Clinical Microbiology, 2008
- Bioinformatics prediction of HIV coreceptor usageNature Biotechnology, 2007
- Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor TropismAntimicrobial Agents and Chemotherapy, 2007
- Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 ActivityAntimicrobial Agents and Chemotherapy, 2005
- Epidemiology and Predictive Factors for Chemokine Receptor Use in HIV‐1 InfectionThe Journal of Infectious Diseases, 2005
- Assessing chemokine co-receptor usage in HIVCurrent Opinion in Infectious Diseases, 2005
- Determination of Coreceptor Usage of Human Immunodeficiency Virus Type 1 from Patient Plasma Samples by Using a Recombinant Phenotypic AssayJournal of Virology, 2001