HIV‐1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation

• Published in: HIV medicine Vol. 7; no. 5; pp. 294 - 298
• Main Authors: Boucher, S, Recordon‐Pinson, P, Ragnaud, JM, Dupon, M, Fleury, H, Masquelier, B
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-2006
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral - genetics; France; HIV Infections - genetics; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV‐1 drug resistance; Human immunodeficiency virus 1; Humans; K65R; Mutation; nucleoside reverse transcriptase inhibitors; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; tenofovir; France
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/j.1468-1293.2006.00379.x

Background
The K65R HIV‐1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations.
Objectives
The aims of this study were: (i) to determine the prevalence of the K65R mutation in a cohort of antiretroviral‐treated patients; (ii) to study genotypic patterns and treatment characteristics in patients in whom the K65R mutation was present.
Study design
We included in the study all antiretroviral‐experienced patients followed up at the Bordeaux University Hospital in 2003 and 2004 for whom an HIV‐1 genotypic resistance analysis was available. Information on RT resistance mutations was reported from a hospital database including therapeutic and biological parameters. The prevalence of K65R was investigated for all patients. Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation.
Results
The prevalence of K65R was 1.9% (26 of 1404 patients). K65R was associated with nucleoside RT inhibitor‐based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients, respectively. The M184V and Q151M mutations were the most commonly co‐selected substitutions. Thymidine analogue mutations (TAMs) were rarely co‐selected with K65R and inversely associated with K65R.
Conclusion
The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs.