|
|
14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. ThOrB1385
BACKGROUND: We evaluated genotype interpretations from clinical specimens by an international panel of experts. We tested the ability to predict assayed phenotype, agreement between experts in predicting phenotype, antiretroviral drug activity and consistency of treatment recommendations.
METHODS: We randomly selected 50 genotypes from the VIRCO database with matching phenotype. The isolates had to be resistant to at least one drug (IC50 >4-fold). For each genotype, experts were asked to predict the susceptibility to each of 16 antiretrovirals (ARV's) as a categorical fold-change (FC) in IC50 (<2.5; 2.5-<4; 4-<7; 7-<10; 10-<20; >20). Expected drug activity was rated on a 6 point scale and experts noted whether or not the ARV would be recommended for use in treatment.
RESULTS: 12 experts interpreted 50 genotypes. Accuracy in predicting FC varied within nRTI's from 25% for abacavir to 74% for 3TC; within PI's it varied from 26% for NFV to 40% for LPV/r. Experts were able to predict FC for NNRTI's about 2/3's of the time. Median difference between predicted FC and assayed FC category was 0 (ie no difference) for all drugs except AZT, D4T, DDI, DDC and ABC where the median difference was +1 category. The correlation (rho) between experts in predicting phenotype ranged from 0.23 for TDF to 0.84 for 3TC for nucleos/tide analogs, from 0.89 for EFV to 0.93 for NVP for NNRTI's and 0.68 for APV to 0.79 for IDV and RTV for PI's. The inter-expert correlation in predicting drug activity showed a similar range and pattern as predicted phenotype. Consensus between experts on treatment recommendations ranged from 62% for DDI to 90% for 3TC with a median of 79%.
CONCLUSIONS: This panel was able to predict phenotype FC within a relatively narrow range. However, experts systematically overestimated the FC for AZT, d4T, ddI, ddC, and ABC. Inter-expert agreement in predicting FC, predictions of drug activity and treatment recommendations was high but varied by ARV.
Presenting author: A R Zolopa
1 Stanford University 1101 welch road, suite a3, Palo Alto, CA, United States 94025
2 Stanford University 1101 welch road, suite a3, Palo Alto, CA, United States 94025
3 Tibotec-Virco, Durham ,NC, United States
4 Harvard University, Boston, MA, United States
020707
ThOrB1385
Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.
