NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain.
BACKGROUND
Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain.


METHODS
We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014-2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/).


RESULTS
In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p<0.001], respectively). Both the prevalence of Q80K and GT1a clade I were not uniform throughout the country (p<0.001), which ranged from 7.3%-22.2% and 15.7%-42.5%, respectively. The frequency of the Q80K polymorphism was far higher in patients infected with GT1a clade I than in patients infected with GT1a clade II (41.5% vs. 1.6%; p<0.001).


CONCLUSIONS
The prevalence of most resistance-associated variants in NS3 was low in patients infected with HCV GT1a in Spain, except for Q80K (11.1%), which was also notably higher in HIV/HCV-coinfected patients. The vast majority of Q80K polymorphisms were detected in GT1a clade I.
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
María Ángeles
MÁ
Jimenez-Sousa
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Mónica
M
Gutiérrez-Rivas
Preventive Medicine and Public Health Unit, Faculty of Health Sciences, Rey Juan Carlos College, Alcorcón, Madrid, Spain.
Alejandro
A
Álvaro-Meca
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Mónica
M
García-Álvarez
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
P Richard
PR
Harrigan
Diagnostic Approach Area, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Cesare Giovanni
CG
Fedele
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Verónica
V
Briz
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Sonia
http://orcid.org/0000-0002-0977-741X
S
Vázquez-Morón
Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Salvador
S
Resino
J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19741
25397486
Curr Opin Infect Dis. 2013 Feb;26(1):66-72
23242342
Antivir Ther. 2015 ;20(8):865-9
25920764
J Infect Dis. 2015 Apr 15;211(8):1288-95
25389307
Hepatol Res. 2016 May;46(6):552-8
26355704
Curr HIV Res. 2012 Oct;10(7):557-71
22973853
J Antimicrob Chemother. 2012 Apr;67(4):984-7
22258932
J Viral Hepat. 2011 Sep;18(9):608-18
20565573
J Clin Virol. 2015 Apr;65:50-3
25766988
Hepatology. 2015 Nov;62(5):1623-32
26095927
Clin Microbiol Infect. 2015 Nov;21(11):1033-9
26232533
Antivir Ther. 2015;20(3):281-7
25279715
AIDS. 2013 Sep 24;27(15):2485-8
23770494
Antimicrob Agents Chemother. 2014 Oct;58(10):6079-92
25092699
Antiviral Res. 2015 Apr;116:10-6
25614456
J Hepatol. 2014 Feb;60(2):392-420
24331294
Arch Virol. 2015 Nov;160(11):2881-5
26249823
Antimicrob Agents Chemother. 2010 Dec;54(12):5288-97
20855726
J Viral Hepat. 2015 Nov;22(11):861-70
26083155
Clin Microbiol Infect. 2016 Apr;22(4):386.e1-3
26706617
J Viral Hepat. 2016 Nov;23 (11):840-849
26775769
J Clin Virol. 2014 Sep;61(1):149-51
25027573
J Hepatol. 2016 Feb;64(2):486-504
26409317
Open Forum Infect Dis. 2015 Mar 31;2(2):ofv043
26213689
J Hepatol. 2015 May;62(5):1008-14
25445400