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

Smit, Erasmus and White, Ellen and Clark, Duncan and Churchill, Duncan and Zhang, Hongyi and Collins, Simon and Pillay, Deenan and Sabin, Caroline and Nelson, Mark and Winston, Alan and Jose, Sophie and Tostevin, Anna and Dunn, David T (2017) An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The Journal of antimicrobial chemotherapy. ISSN 1460-2091.

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Official URL: https://academic.oup.com/jac/article/3098563/An-as...

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.

Item Type: Article
Subjects: W Public health. Health statistics. Occupational health. Health education
WC Communicabable diseases
Divisions: Clinical Support > Infectious Diseases
Related URLs:
Depositing User: Mr Philip O'Reilly
Date Deposited: 31 May 2017 14:37
Last Modified: 31 May 2017 14:37
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1379

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