000 02326cam a2200205 4500
001 NMDX7453
008 120401t2017 xxu||||| |||| 00| 0 eng d
100 _aAinsworth, J.
240 _aJournal of Antimicrobial Chemotherapy
245 _aAn association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs
260 _c2017
500 _aNMUH Staff Publications
500 _aEMBASE
500 _a72
520 _a<span style="font-size: 10pt;">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. </span>
700 _aSchwenk, A.
700 _aMiller, S.
700 _aWood, C.
856 _uhttps://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkx091
999 _c76348
_d76348