Comparison of genotyping and phenotyping methods for determining susceptibility of HIV-1 to antiretroviral drugs.
OBJECTIVE
To compare antiretroviral resistance susceptibility testing of patient HIV-1 strains using genotype and phenotype methods.


METHODS
Eighteen plasma samples with viral load > 2000 HIV-1 RNA copies/ml were randomly selected for testing by both methods. Disease and treatment data were available for all patients.


METHODS
Samples were analysed genotypically using a kit assay (HIV-1 Genotyping Systems, Applied Biosystems), performed by the Clinical Research Laboratory at Macfarlane Burnet Centre for Medical Research. Samples were analysed phenotypically using a rapid phenotypic assay (PhenoSenseTM HIV, ViroLogic), performed by the manufacturer. Results from both methods were interpreted using a defined protocol. Each susceptibility assay was performed and interpreted by individuals unaware of either the clinical data or the results of the other susceptibility assay. Concordance was defined categorically as either the presence of reduced susceptibility (> 2.5-fold change) in the phenotypic assay and resistance associated mutations in the genotypic assay, or the absence of these findings in both assays.


RESULTS
Concordance between phenotypic and genotypic susceptibility testing was 81% for nucleoside reverse transcriptase inhibitors, 91% for non-nucleoside reverse transcriptase inhibitors and 90% for protease inhibitors. Complete concordance between phenotype and genotype for all 14 drugs evaluated was observed in three (17%) patient samples.


CONCLUSIONS
Phenotypic and genotypic susceptibility appear to provide similar results. However, interpretation of genotypic results can be complicated, and both methods still require clinical validation.
Dunne
A L
AL
Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.
Mitchell
F M
FM
Coberly
S K
SK
Hellmann
N S
NS
Hoy
J
J
Mijch
A
A
Petropoulos
C J
CJ
Mills
J
J
Crowe
S M
SM
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D010641:Phenotype; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors