Journal Article

Comparative evaluation of three computerized algorithms for prediction of antiretroviral susceptibility from HIV type 1 genotype

Maurizio Zazzi, Laura Romano, Giulietta Venturi, Robert W. Shafer, Caroline Reid, Federico Dal Bello, Cristina Parolin, Giorgio Palù and Pier E. Valensin

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 2, pages 356-360
Published in print February 2004 | ISSN: 0305-7453
Published online February 2004 | e-ISSN: 1460-2091 | DOI:
Comparative evaluation of three computerized algorithms for prediction of antiretroviral susceptibility from HIV type 1 genotype

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Objectives: To compare three methods for using HIV-1 genotype to predict antiretroviral drug susceptibility.

Methods: We applied three genotypic interpretation algorithms to 478 reverse transcriptase (RT) and 410 protease sequences for which phenotypic data were available. Sequences were obtained from clinical practice and from published sequences in the Stanford HIV-1 RT and Protease Sequence Database. The genotypic interpretation algorithms included: Stanford HIVdb program (HIVdb), the Visible Genetics/Bayer Diagnostics Guidelines 6.0 (VGI) and a genotypic interpretation program (AntiRetroScan, ARS) developed at the University of Siena, Italy. Genotypic interpretations were normalized to a three-level output: susceptible, intermediate and resistant. Discordances were defined as differences between genotype and phenotype for the same virus isolate. Discordances for which an isolate was considered susceptible by one test but resistant by another test were considered major discordances.

Results: The frequency of major discordances between genotype and phenotype was 10.6, 13.7 and 15.7% for ARS, VGI and HIVdb, respectively (P < 0.0001 for ARS versus HIVdb and for ARS versus VGI; P = 0.002 for VGI versus HIVdb). The correlation between genotype and phenotype was highest for non-nucleoside RT inhibitors and lowest for nucleoside RT inhibitors. Half of the major discordances involved stavudine, didanosine and zalcitabine. The concordance among the three genotypic algorithms was high, with weighted Kappa values ranging between 0.76 and 0.84 for the pairwise comparisons between each of the algorithms.

Conclusions: Genotype interpretation algorithms correctly predict phenotype in 85–90% of cases, but the rate of concordance is not uniformly distributed among different drugs. These data provide insight into the potential additional benefit derived from phenotyping.

Keywords: Keywords: antiretroviral drug resistance, genotype, phenotype, virtual phenotype

Journal Article.  2997 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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