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

On behalf of the UK HIV Drug Resistance Database and the UK Collaborative HIV Cohort

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6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2075-2082
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017

Bibliographical note

Funding Information:
The UK Collaborative HIV Cohort (CHIC) Study and the UK HIV Drug Resistance Database are funded by the Medical Research Council (MRC) UK (Grant Numbers G0000199, G0600337, G0900274 and M004236).

Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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