Background. Resistance testing is considered standard of care in HIV medicine, but there is no standard interpretation system for genotype tests. We sought to determine how much agreement exists within a group of experts in the interpretation of complex genotypes. Methods. Genotypes from clinical specimens were sent to an international panel of 12 resistance experts. Phenotypic susceptibility testing of these clinical isolates was performed with antivirogram. Experts predicted phenotype fold change category (< 2.5-fold change, 2.5-4.0-fold change, > 4.0- to 7.0-fold change, > 7.0- to 10-fold change, > 10- to 20-fold change, or > 20-fold change) and predicted expected drug activity for each of 16 antiretroviral drugs. Experts were also asked to make treatment recommendations on the basis of the genotype. Results. The experts predicted the exact phenotype fold change category correctly 44% of the time, but they varied widely by antiretroviral drug (range, 25%-74%). The highest accuracy was observed for lamivudine (74%) and the nonnucleoside reverse transcriptase inhibitors (66%-69%). Experts generally predicted higher levels of resistance to the remaining nucleoside reverse transcriptase inhibitors than what was found by phenotypic testing. Agreement among experts in predicting phenotype fold change category ranged widely depending on the drug (median agreement, 42% [range, 28%-74%]); the same pattern was observed in predicting expected drug activity (median agreement, 45% [range, 32%-87%]). Experts agreed on treatment recommendations in a median of 79% of instances, and recommendations were consistent over time, with blinded retesting. Conclusions. Although their ability to predict phenotype from a genotype varied for individual antiretroviral drugs, this expert panel had a high degree of agreement in deriving treatment recommendations from the genotype.

Zolopa, A., Lazzeroni, L., Rinehart, A., Vezinet, F., Clavel, F., Collier, A., et al. (2005). Accuracy, precision, and consistency of expert HIV type 1 genotype interpretation: An international comparison (the GUESS Study). CLINICAL INFECTIOUS DISEASES, 41(1), 92-99 [10.1086/430706].

Accuracy, precision, and consistency of expert HIV type 1 genotype interpretation: An international comparison (the GUESS Study)

PERNO, CARLO FEDERICO;
2005-01-01

Abstract

Background. Resistance testing is considered standard of care in HIV medicine, but there is no standard interpretation system for genotype tests. We sought to determine how much agreement exists within a group of experts in the interpretation of complex genotypes. Methods. Genotypes from clinical specimens were sent to an international panel of 12 resistance experts. Phenotypic susceptibility testing of these clinical isolates was performed with antivirogram. Experts predicted phenotype fold change category (< 2.5-fold change, 2.5-4.0-fold change, > 4.0- to 7.0-fold change, > 7.0- to 10-fold change, > 10- to 20-fold change, or > 20-fold change) and predicted expected drug activity for each of 16 antiretroviral drugs. Experts were also asked to make treatment recommendations on the basis of the genotype. Results. The experts predicted the exact phenotype fold change category correctly 44% of the time, but they varied widely by antiretroviral drug (range, 25%-74%). The highest accuracy was observed for lamivudine (74%) and the nonnucleoside reverse transcriptase inhibitors (66%-69%). Experts generally predicted higher levels of resistance to the remaining nucleoside reverse transcriptase inhibitors than what was found by phenotypic testing. Agreement among experts in predicting phenotype fold change category ranged widely depending on the drug (median agreement, 42% [range, 28%-74%]); the same pattern was observed in predicting expected drug activity (median agreement, 45% [range, 32%-87%]). Experts agreed on treatment recommendations in a median of 79% of instances, and recommendations were consistent over time, with blinded retesting. Conclusions. Although their ability to predict phenotype from a genotype varied for individual antiretroviral drugs, this expert panel had a high degree of agreement in deriving treatment recommendations from the genotype.
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
abacavir; amprenavir; antiretrovirus agent; delavirdine; didanosine; efavirenz; indinavir; lamivudine; lopinavir plus ritonavir; nelfinavir; nevirapine; ritonavir; RNA directed DNA polymerase inhibitor; saquinavir; stavudine; tenofovir; zalcitabine; zidovudine; accuracy; article; controlled study; drug activity; drug sensitivity; genotype; Human immunodeficiency virus 1; nonhuman; phenotype; priority journal; Anti-HIV Agents; Data Interpretation, Statistical; Drug Resistance, Viral; Genotype; HIV Infections; HIV Protease; HIV Protease Inhibitors; HIV-1; HIV-1 Reverse Transcriptase; Humans; Internationality; Microbial Sensitivity Tests; Mutation; Phenotype; Reverse Transcriptase Inhibitors
Zolopa, A., Lazzeroni, L., Rinehart, A., Vezinet, F., Clavel, F., Collier, A., et al. (2005). Accuracy, precision, and consistency of expert HIV type 1 genotype interpretation: An international comparison (the GUESS Study). CLINICAL INFECTIOUS DISEASES, 41(1), 92-99 [10.1086/430706].
Zolopa, A; Lazzeroni, L; Rinehart, A; Vezinet, F; Clavel, F; Collier, A; Conway, B; Gulick, R; Holodniy, M; Perno, Cf; Shafer, R; Richman, D; Wainberg, M; Kuritzkes, D
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

Questo articolo è pubblicato sotto una Licenza Licenza Creative Commons Creative Commons

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/42114
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 8
social impact