16th International HIV Drug Resistance Workshop 12-16 June 2007, Barbados

THE K65R MUTATION IS RARELY DETECTED AS A MINORITY QUASISPECIES IN THERAPY-NAÏVE, CHRONICALLY HIV-1-INFECTED PERSONS

Antivir Ther. 2007; 12:S52 (abstract no. 45)

KJ Metzner ¹, H Walter¹, P Rauch¹, P Braun², H Knechten², R Ehret², M Mueller³, S Klauke⁴, J van Lunzen⁵ and B Ranneberg^6
1University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany; ²Praxis Zentrum Blondelstrasse, Aachen, Germany; ³Praxis Schwabstrasse 26, Stuttgart, Germany; ⁴Infektiologikum Frankfurt, Frankfurt, Germany; ⁵University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; ⁶Gilead Sciences, Martinsried, Germany

BACKGROUND: The prevalence of drug-resistant HIV-1 as a major virus population in therapy-naïve patients has an impact on the success of antiretroviral therapy (ART). Minority quasispecies of drug-resistant HIV-1 cannot be detected by conventional genotyping, however, it has been shown that those low-frequency mutations can also impair ART. The K65R mutation of the reverse transcriptase is associated with resistance against tenofovir (TDF) and other NRTIs. Thus, we retrospectively analysed the prevalence of the K65R mutation as minority quasispecies in baseline samples from patients receiving first line ART including Truvada (TDF + FTC) and a boosted protease inhibitor or an NNRTI.

METHODS: 194 patients from several clinical centres in Germany were included in this study. Baseline samples before ART were collected between April 2005 and August 2006. Minority quasispecies of K65R variants were detected by allele-specific real-time PCR (AS-PCR) with a discriminative power of 0.4%.

RESULTS: The K65R mutation was detected in 4/194 patients (2.1%). This variant represented minority quasispecies of 0.8 ±0.0%, 2.1 ±0.5%, 15.4 ±3.4% and 21.4 ±0.9% of plasma viral genomes, respectively. Using conventional population sequencing, the K65R mutation was not detected in any patient. The 24 week data in regard to efficacy revealed that three of these four patients did not experience therapy failure. The viral load of the fourth patients did never fall below the detection limit of 40 HIV-1 RNA copies/ml plasma; however, this was due to non-compliance.

CONCLUSIONS: The K65R mutation is very uncommon in therapy-naïve, chronically infected patients. The prevalence of the K65R mutation as a minority quasispecies before ART seems not to be associated with virological therapy failure in patients initiating ART with Truvada and a third agent.

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2007-06-12
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