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Original article

Predicting antiretroviral drug resistance from the latest or the cumulative genotype

Federico Garcia, Marta Alvarez, Zoe Fox, Ana Garcia-Diaz, Vicente Guillot, Margaret Johnson, Natalia Chueca, Andrew Phillips, José Hernández-Quero, Anna Maria Geretti

Corresponding author name: Anna Maria Geretti
Corresponding author e-mail: a.geretti@medsch.ucl.ac.uk

Citation: Antiviral Therapy 2011; 16:373-382
doi: 10.3851/IMP1753

Date accepted: 24 September 2010
Date published online: 15 March 2011

Abstract

Background: This study evaluates the added benefit when estimating antiretroviral drug resistance of combining all available resistance test results in a cumulative genotype relative to using the latest genotype alone.

Methods: The prevalence of resistance and genotypic sensitivity scores (GSS) predicted by the latest and the cumulative genotype, together with virological outcomes after the latest genotype, were measured in treatment-experienced patients who underwent ≥2 resistance tests in 1999–2008.

Results: Comparing the latest with the cumulative genotype in 227 patients, 4 (1.7%) versus 0 (0.0%) showed no major resistance mutations, whereas 74 (32.6%) versus 46 (20.3%), 88 (38.8%) versus 76 (33.5%) and 61 (26.9%) versus 105 (46.3%) showed single-class, dual-class and triple-class resistance mutations, respectively. The median (IQR) number of fully or partially active drugs was 6 (5–6) versus 5 (4–6) for the nucleoside/nucleotide reverse transcriptase inhibitors, 3 (1–3) versus 1 (1–3) for the non-nucleoside reverse transcriptase inhibitors and 7 (7–7) versus 7 (7–7) for the protease inhibitors, respectively. Among 163 patients who started a new regimen after the latest genotype, both the latest and the cumulative GSS were predictive of early (≤24 weeks) virological responses. The GSS decreased by median 1 unit (IQR 0.5–1.0) in the cumulative genotype and larger differences relative to the latest genotype corresponded to smaller decreases in viral load.

Conclusions: The cumulative genotype offers a more comprehensive evaluation of the burden of resistance. This approach can guide small but appreciable improvements in the selection of antiretroviral regimens for treatment-experienced patients.

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