Analysis of discrepancies in the interpretation of antiretroviral drug resistance results in HIV-1 infected patients of Basque Country, Spain

Background: Genotypic and phenotypic analysis of HIV-1 resistance mutations constitute one important point for providing guidelines in the choice of antiretroviral regimens and to design lines of rescue treatment for patients holding HIV-1 drug-resistant variants. However, some levels of discordance among them has been described. Objectives: (i) To compare the genotypic analysis of resistance mutations to reverse transcriptase (RT) and protease (PR) inhibitors by Stanford HIVdb program (http:/hivdb.stanford.edu) (St-HIVdb), and genotype with quantitative phenotypic analysis (Virtual Phenotype (TM), VircoNET). (ii) To identify drug resistance mutations associated with discrepant results. Study design: Five hundred HIV-1 infected patients were included in this study. RNA was extracted from plasma. RT and PR regions were amplified and sequenced using ABI-Prism DNA sequencing system. Sequences were corrected and assembled with Seqman and Bioedit computer programs. The corrected sequences were submitted to the Stanford HIV-Seq program (http:/hivdb.stanford.edu) and to Virtual Phenotype (TM) (VircoNET). Results: Discrepant cases were considered if results were high or intermediate resistant by Stanford HIV-Seq program and susceptible by Virtual Phenotype (TM), being detected as follows: (i) nucleoside RT inhibitors (NRT): 31.7% (ABC) 31% (d4T), 29.5% (ddC), 27.6% (ddI), 14.3% (TDF) and 11.3% (ZDV) and to PR inhibitors: 8.8% (SQV), 5% (APV), 3.8% (NFV) and 3.2% (IDV). These discrepant results were related to the presence of thymidine analogue mutations (TAMs) and also to key resistance mutations to NRT inhibitors: 65R, 69D/N, 74V/I, 184V/I and 215Y/F. (ii) PR inhibitors: 82A/F/T/S, 84I and 90M. Concordant results were considered when the interpretations by both programs were coincident, being higher than 96.7% for non-NRT inhibitors. Conclusions: The detection of discrepant results to NRT inhibitors and PR inhibitors, including the analysis of sequences with key resistant mutations to some drugs, means that further investigation is necessary in order to establish which is the best interpretation system as antiretroviral therapy guide. (c) 2004 Elsevier B.V. All rights reserved.