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Accuracy, Precision and Consistency of HIV-1
Genotype Interpretation by Experts
Resistance
testing
is considered standard of care in HIV medicine,
but there is no standard interpretation system
for genotype
tests. The authors of the present study sought to
determine how much agreement exists within
a group of experts in the interpretation of
complex genotypes.
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. ·
The
highest accuracy was observed for lamivudine (Epivir)
(74%) and the non
nucleoside reverse transcriptase inhibitors [NNRTIs]
(66% 69%).
·
Experts
generally predicted higher levels of resistance
to the remaining nucleoside
reverse transcriptase inhibitors (NRTIs) 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%).
·
The
same pattern was observed in predicting expected
drug activity (median agreement, 45%.
·
Experts
agreed on treatment recommendations in a median
of 79% of instances, and recommendations were
consistent over time, with blinded retesting.
Based
on these findings, the authors conclude, “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.”
Stanford
University School of Medicine
and Veterans Affairs Palo
Alto Healthcare System, Palo
Alto, and Veterans Affairs
San Diego Healthcare System
and University of California,
San Diego, California; University
of Washington School of
Medicine, Seattle; Weill Medical
College of Cornell University,
New York; Section of
Retroviral Therapeutics, Brigham
and Women's Hospital and
Division of AIDS, Harvard
Medical School, Boston, Massachusetts;
Tibotech-Virco, Mechelen, Beligum;
Bichat Hospital University and
Inserm U552, Hospital Bichat-Claude
Bernard, Paris, France; McGill
University AIDS Center, Montreal,
Quebec, and University of
British Columbia, Canada; and
University of Rome Tor
Vergata, Italy.
06/13/05
Reference
A R Zolopa and others.
Accuracy, Precision, and Consistency
of Expert HIV Type 1
Genotype Interpretation: An International
Comparison (The GUESS Study).
Clinical Infectious Diseases 41(1): 92-99. July 1, 2005.
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