An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs

Smit, E. et al. (2017) An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Journal of Antimicrobial Chemotherapy, 72(7), pp. 2075-2082. (doi: 10.1093/jac/dkx091) (PMID:28379449)

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Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients (n = 3410) were mostly MSM (78%) and those with subtype C (n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55–2.62, P < 0.001). Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Clark, Dr Duncan
Authors: Smit, E., White, E., Clark, D., Churchill, D., Zhang, H., Collins, S., Pillay, D., Sabin, C., Nelson, M., Winston, A., Jose, S., Tostevin, A., and Dunn, D. T.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Antimicrobial Chemotherapy
Publisher:Oxford University Press
ISSN (Online):1460-2091
Published Online:03 April 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Antimicrobial Chemotherapy 72(7):2075-2082
Publisher Policy:Reproduced under a Creative Commons License

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