Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection
Faydra I. Lieveld†,‡, Niels Swaans*, Astrid M. Newsum§,||, Cynthia K.Y. Ho§, Janke Schinkel§, Richard Molenkamp§, Jan T.M. van der Meer¶, Joop E. Arends‡, Andy I.M. Hoepelman‡, Anne M.J. Wensing*, Peter D. Siersema†,**, Karel J. van Erpecum†, Greet J. Boland
,
Corresponding author
* Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands
† Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
‡ Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands
§ Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands
¶ Department of Internal Medicine and Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands
|| Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands
** Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
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"apellidos" => "Hoepelman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">‡</span>" "identificador" => "aff0015" ] ] ] 9 => array:3 [ "nombre" => "Anne M.J." "apellidos" => "Wensing" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff0005" ] ] ] 10 => array:3 [ "nombre" => "Peter D." "apellidos" => "Siersema" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff0035" ] ] ] 11 => array:3 [ "nombre" => "Karel J. van" "apellidos" => "Erpecum" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "aff0010" ] ] ] 12 => array:4 [ "nombre" => "Greet J." "apellidos" => "Boland" "email" => array:1 [ 0 => "g.j.boland@umcutrecht.nl" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands" "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands" "etiqueta" => "†" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands" "etiqueta" => "‡" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands" "etiqueta" => "§" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Internal Medicine and Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands" "etiqueta" => "¶" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands" "etiqueta" => "||" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands" "etiqueta" => "**" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 306 "Ancho" => 488 "Tamanyo" => 11636 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Number of NS3 resistance-associated variants in the HIV-infected and HIV-uninfected study population. Number of RAVs per subject with interquartile range: 1 (0-1) for HIV-infected vs.1 (1-2) for HIV-uninfected. Black dots represent HIV-infected and open dots represent HIV-uninfected subjects. HIV: human immunodeficiency virus. no: number. RAVs: resistance-associated variants.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">With the introduction of interferon-free direct-acting antivirals (DAAs), sustained virologic response (SVR) rates increased substantially for hepatitis C virus (HCV) infected patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> As approximately 30% of patients with human immunodeficiency virus (HIV) are infected with HCV,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> coinfected patients form a significant proportion of patients eligible for treatment with DAAs. Nevertheless, only limited data are available on HCV genetic polymorphisms in HIV/HCV coinfected patients (summarized in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>). The emergence of NS3 resistance-associated variants (RAVs) such as Q80K has been described in HCV patients, especially in those with genotype 1a.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Successful therapy could be complicated by the high genetic diversity of HCV and its rapid mutation rate.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Notably, occurrence rates of RAVs vary in different parts of the world, with a higher frequency of Q80K in North America than Europe, and a high variation in reported prevalence of Q80K (ranging from 0% to 18%) between individual European countries.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This may be related to the high prevalence of genotype 1a in North America compared to Europe, where genotype 1b is more frequent.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Moreover, within genotype 1a, two distinct clades (clade I and clade II) are distinguished, and Q80K presence appears to be restricted to clade I.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Several studies reported reduced susceptibility to NS3/4A protease inhibitors in the presence of RA<span class="elsevierStyleItalic">Vs</span>.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Q80K exhibited a 10.9 fold reduced susceptibility to simeprevir <span class="elsevierStyleItalic">in vitro</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and is reported to jeopardize achievement of SVR in the combination of the NS3/4A protease inhibitor simeprevir with pegylated-interferon and ribavirin.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In “all oral” DAA regimens with NS3A, NS5A and/or NS5B inhibitors, effects of Q80K seem to be minor or non-existent.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleItalic">In vitro</span>, for S122R, the sensitivity to simeprevir appears to be reduced by up to 20 fold.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In addition, the N174 polymorphisms are reported to lead to 3.3–5.9 fold susceptibility reduction to telaprevir and boceprevir <span class="elsevierStyleItalic">in vitro</span>.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0010" class="elsevierStylePara elsevierViewall">RAVs may form a high burden within the HIV-infected population because HCV subtype 1a is more prevalent in coinfected patients<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and more prone to NS3 drug resistance than other subtypes.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Nevertheless, it remains to be determined to what extent NS3 RAVs impact treatment results in HCV patients with and without HIV infection, during treatment with interferon-free DAA regimens. While several studies have focused on RAVs in HIV-uninfected HCV patients, few studies assessed frequencies of NS3 RAVs in HIV/HCV coinfected patients with conflicting results.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">In the current study we analyze the frequencies of NS3 RAVs in HCV genotype 1a patients with and without HIV. In addition, we assess the distribution of NS3 RAVs between clade I and II viruses.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Patients and samples</span><p id="p0020" class="elsevierStylePara elsevierViewall">A total of 148 samples from HCV genotype 1a patients were available from the University Medical Center Utrecht (UMCU) and the Academic Medical Center (AMC) in the Netherlands. Samples consisted of pretreatment archived samples from the CIRA study<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> (all HIV uninfected) and samples from patients (previously) in regular care. Patients treated with NS3/4A protease inhibitors, NS5A or NS5B polymerase inhibitors, or patients treated with experimental therapy prior to sampling have been excluded. In addition, demographic and clinical data were collected.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Sequencing procedure</span><p id="p0025" class="elsevierStylePara elsevierViewall">HCV RNA was isolated using the MagNA Pure 96 system (Roche Applied Sciences). A reverse transcription PCR was then performed using either the Superscript III One-Step Platinum Taq kit (Life Technologies, Inc., Gaithersburg, MD) with HCV genotype 1-specific primers (UMCU) or Superscript II (Life Technologies) with random hexamer primers (AMC). Subsequently, cDNA was amplified by nested PCR using either the Expand High Fidelity PCR System Kit (Roche Diagnostic) (UMCU) or Faststart Taq polymerase (Roche Applied Science) (AMC). Product length was confirmed on an agarose gel. When required, the product was purified using a QIAquick PCR purification kit (Qiagen Inc.). A cycle sequence reaction was run using the BigDye Terminator v3.1 sequencing kit (Technologies, Inc., Gaithersburg, MD) to prepare the samples for sequencing. After cycle sequence reactions, samples were sequenced using the 3730xl DNA analyzer (Applied Biosystems), covering NS3 amino acids 1-181. Both reverse transcriptase PCR protocols and nested PCR procedures were compared in 14 random samples and yielded similar results. The following amino acid positions were selected for RAV analyses (selected a-priori according to previous literature<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>) by using geno2pheno [hcv] 0.92 with a fold change cutoff value of 1.2: V36, Q41, F43, T54, V55, Q80, V107, R109, S122, V132, R155, A156, V158, D168, V/I170, N174 and L/M175.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Statistical analyses</span><p id="p0030" class="elsevierStylePara elsevierViewall">Presence of RAVs were compared between HIV-infected and HIV-uninfected groups, clade I and clade II viruses and samples taken before and after 2010. Additional sensitivity analyses were performed for RAV prevalences in samples taken before and after 2008, 2009 and 2011. Data were compared using non-parametric χ<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>, Fisher’s exact or Mann-Whitney U tests as appropriate. Qualitative data were summarized by numbers with percentages and quantitative data by medians with ranges. Statistical analyses were performed using SPSS statistics version 21.0.0 (IBM SPSS Statistics, Chicago, IL) and graphics were created using GraphPad Prism version 6.0 (GraphPad Software Inc., CA, USA). A two sided p-value of < 0.05 was considered statistically significant.</p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Results</span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Study population</span><p id="p0035" class="elsevierStylePara elsevierViewall">The NS3 region was sequenced in 148 unique samples from HCV genotype 1a infected patients (n = 68 HIV respectively n = 80 non-HIV). All samples were collected between 2000 and 2015. HIV status from all subjects was known, however, clinical data was incomplete in 19 subjects with sample dates between 2000 and 2004. Samples from HIV-infected patients were more frequently taken at later dates than those from HIV-uninfected (median 2011 (range 2003-2015) <span class="elsevierStyleItalic">vs.</span> 2008 (2000-2015), p = 0.04). HIV-infected patients were more frequently younger, male, acquired HCV more often through sexual contact (men who have sex with men (MSM)) and had higher baseline alanine aminotransferase levels (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>). HIV-uninfected patients were more likely to have acquired HCV through injection drug use or by unknown causes and had more frequently cirrhosis at baseline (diagnosis by FibroScan®, liver biopsy or imaging modalities). Of the 50 HIV-infected subjects treated with combined antiretroviral therapy, 41 (82%) had undetectable HIV RNA (< 50 copies/mL).</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">RAVs in the study population</span><p id="p0040" class="elsevierStylePara elsevierViewall">Polymorphisms at positions F43, R109, V132, S138, R155, V158, D168 and L/M175 were not observed. While samples from HIV-infected were more frequently of recent dates than those from HIV-uninfected patients, presence of at least one RAV did not differ between samples taken before or after 2010, neither in the HIV-infected group (62% <span class="elsevierStyleItalic">vs.</span> 62%, p = 1.0), nor in the HIV-uninfected group (78% <span class="elsevierStyleItalic">vs.</span> 80%, p = 1.0), nor in the whole group (72% <span class="elsevierStyleItalic">vs.</span> 70%, p = 1.0). In addition, prevalence of V36, Q41, T54, V55, Q80K, V107, S122, A156, V/I170 and N174 polymorphisms were not significantly different between samples taken before and after 2010. In sensitivity analyses, no differences were seen in samples taken before and after 2008, 2009 and 2011. As a proxy of duration of HCV infection, presence of RAVs between patients with and without cirrhosis was assessed, with no significant differences found in those with HIV (67% <span class="elsevierStyleItalic">vs.</span> 63%, p = 1.0), those without HIV (74% <span class="elsevierStyleItalic">vs.</span> 80%, p = 0.74) or in the whole group (72% <span class="elsevierStyleItalic">vs.</span> 69%, p = 1.0).</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">RAVs in HIV infected <span class="elsevierStyleItalic">vs.</span> HIV uninfected groups</span><p id="p0045" class="elsevierStylePara elsevierViewall">Overall, HIV-infected patients had lower RAV frequencies than HIV-uninfected patients, with 42 (62%) exhibiting at least one RAV <span class="elsevierStyleItalic">vs.</span> 63 patients (79%, p = 0.03) in the HIV-uninfected group (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>). In addition, total number of RAVs per subject was significantly lower in the HIV-infected group (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>). Prevalence of Q80K was higher in HIV-infected patients (50% <span class="elsevierStyleItalic">vs.</span> 24%, p = 0.001), whereas S122D/G/N/S polymorphisms (2% <span class="elsevierStyleItalic">vs.</span> 16%, p = 0.002) and N174G/N/S polymorphisms (10% <span class="elsevierStyleItalic">vs.</span> 55%, p < 0.0001) had lower prevalences (<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>). Within the HIV-infected group, CD4 cell count ≥ 350 or treatment with combined antiretroviral therapy did not affect prevalence of the RA<span class="elsevierStyleItalic">Vs.</span></p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">RAVs distribution among HCV transmission modes</span><p id="p0050" class="elsevierStylePara elsevierViewall">Distribution of RAVs among the various modes of HCV acquisition in the total study population are given in <a class="elsevierStyleCrossRef" href="#t0020">table 4</a>. Significantly higher rates of Q80K were observed in HCV transmission by MSM <span class="elsevierStyleItalic">vs.</span> other modes of transmission (29/58 (50%) <span class="elsevierStyleItalic">vs.</span> 24/90 (27%), p = 0.005). Lower frequencies of Q80K were observed among injection drug users <span class="elsevierStyleItalic">vs.</span> other modes of HCV transmission (4/25 (16%) <span class="elsevierStyleItalic">vs.</span> 49/123 (40%), p = 0.024). S122 and N174 polymorphisms displayed lower frequencies in MSM than in other modes of transmission (For S122 1/58 (2%) <span class="elsevierStyleItalic">vs.</span> 13/90 (14%) with p = 0.009, and for N174 45/90 (50%) <span class="elsevierStyleItalic">vs.</span> 6/58 (10%) with p < 0.0001). For all other polymorphisms, no differences in mode of HCV transmission were observed.</p><elsevierMultimedia ident="t0020"></elsevierMultimedia></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">RAVs in clade I <span class="elsevierStyleItalic">vs.</span> clade II viruses</span><p id="p0055" class="elsevierStylePara elsevierViewall">In HIV-infected patients, clade I viruses were significantly more prevalent than clade II viruses (85% <span class="elsevierStyleItalic">vs.</span> 15%), whereas distribution of clade I and clade II viruses was equal in HIV-uninfected subjects (49% <span class="elsevierStyleItalic">vs.</span> 51%, p<0.0001). Q80K was exclusively seen in clade I viruses, whereas S122 polymorphisms (3% <span class="elsevierStyleItalic">vs.</span> 22%, p = 0.001) and N174 polymorphisms (13% <span class="elsevierStyleItalic">vs.</span> 75%, p < 0.0001) had significantly lower relative frequencies in clade I viruses than in clade II viruses (<a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>). No significant differences in prevalence of at least one RAV or CD4 cell count were observed between clade I and clade II viruses.</p><elsevierMultimedia ident="t0025"></elsevierMultimedia></span></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Discussion</span><p id="p0060" class="elsevierStylePara elsevierViewall">In the current study, significant higher frequencies of Q80K and lower frequencies of polymorphisms on the S122 and N174 loci were observed in NS3/4A protease inhibitor treatment-naïve HIV-infected patients than in HIV-uninfected patients with HCV genotype 1a. These results may be explained by differences in HCV acquisition between the groups, as a subset of HCV genotype 1a strains may circulate among the MSM community,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> whereas a broad variety in strains may be acquired through other transmission routes. Indeed, several studies among HIVpositive MSM in European studies, including the Netherlands, revealed the existence of MSM-specific HCV transmission networks in which HCV co-circulating strains were identified.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> This may have been exhibited in the current study by higher Q80K frequencies in the MSM group whereas the other RAVs displayed a more even distribution among the other transmission modes. Another explanation may be the high prevalence of genotype 1a clade I viruses in HIV-infected patients, which may lead to subsequent higher Q80K rates.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In line with our observations, a recent study on NS3 RAVs in HIV-infected patients (n = 40 HCV genotype 1a and n = 19 genotype 1b) observed 10/23 <span class="elsevierStyleItalic">vs.</span> 4/17 RAVs in genotype 1a clade I respectively clade II, of which 8 out of 10 RAVs in clade I were Q80K.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">Q80K reduces susceptibility to simeprevir <span class="elsevierStyleItalic">in vitro</span>, with lower SVR rates especially in pegylated-interferon containing combinations,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and some studies indicate that Q80K may also reduce SVR rates in “all oral” regimens containing simeprevir.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However, guidelines state that combination of simeprevir with other DAAs may mitigate the effects of Q80K,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and as the impact of Q80K seems absent in treatment with newer NS3/4A protease inhibitors,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> the relevance of this polymorphism remains controversial. While S122 polymorphisms are associated with reduced efficacy of simeprevir,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> telaprevir and asunaprevir<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and N174 polymorphisms with reduced efficacy of simeprevir,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> reports suggest that they only have a minor impact on SVR.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">Several studies with smaller sample sizes have evaluated Q80K and other NS3 RAVs in patients with and without HIV<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>,<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>). To our knowledge the current study is the largest, and the first to unequivocally describe higher frequencies of Q80K in HIV-infected patients with HCV genotype 1a. The discrepancies in results with the other studies may be attributed to differences in demographic and geographic characteristics, as well as the smaller sample sizes in other studies. Nonetheless, one study also found higher frequencies of Q80K in coinfected patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> However, that study examined a small group (n = 21) consisting of both HCV genotype 1a and genotype 1b infected subjects.</p><p id="p0075" class="elsevierStylePara elsevierViewall">Currently, a large number of HCV-infected patients have been treated with interferon-free DAA regimens with high success rates, reaching up to 90% and above depending on the regimen.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> While baseline RAV testing may not be relevant in the majority of patients it may still have an important role in individual cases as cross-resistance exists between first- and second-generation NS3/4A protease inhibitors,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> or when other negative treatment predictors such as cirrhosis are present.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">In our study we observed lower number of RAVs per subject in the HIV-infected population, which is in line with another study on this subject.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Another instructive observation from our study is higher prevalence of clade I than clade II viruses in HIV-infected with an equal distribution of clade I and clade II viruses in HIV-uninfected subjects. This is contrary to the findings of another study<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> that found HIV-infected subjects to have a trend towards higher prevalence rates of clade II viruses. In this latter study however, both HIV-infected and HIV-uninfected subjects were most frequently infected by HCV through intravenous drug use or by unknown means as opposed to homosexual contact in our HIV-infected study population. In line with other reports, Q80K was exclusively seen in clade I viruses in our study.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However, we are the first to describe higher prevalence of S122 and N174 polymorphisms in clade II viruses.</p><p id="p0085" class="elsevierStylePara elsevierViewall">Our study has several limitations, including the retrospective design and availability of limited clinical data in some patients. Second, we assessed RAVs by population-based sequencing and do not have deep sequencing data (i.e. mutations expressed in ≥ 20% of the HCV quasispecies population).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> However, a previous study on NS5A RAVs investigating several sequencing cut off values from 1–20%, described a reduction in SVR only in high level resistant polymorphisms.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Thus, the widely used population-based sequencing method is highly likely to be sufficient in detecting clinically relevant RAKs. The strengths of this study are that we analyzed a relatively large subset of NS3 RAVs throughout 15 years of time in both HIV-infected and HIV-uninfected patients and the relatively large sample size compared to the available literature.</p><p id="p0090" class="elsevierStylePara elsevierViewall">In conclusion, the current study demonstrated increased prevalence of Q80K and reduced prevalence of S122 and N174 polymorphisms in HIV-infected patients compared to HIV-uninfected patients with HCV genotype 1a. Although testing for RAVs prior to treatment with NS3/4A protease inhibitors does not constitute standard of care with currently available DAA regimens, it could be useful in the near future when treating DAA-failures or difficult-to-treat patients.</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Abbreviations</span><p id="p0095" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">•</span><p id="p0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AMC:</span> Academic Medical Center.</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DAA:</span> direct-acting antiviral.</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCV:</span> hepatitis C virus.</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HIV:</span> human immunodeficiency virus.</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">•</span><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">MSM:</span> men who have sex with men.</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">•</span><p id="p0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">RAV:</span> resistance-associated variant.</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">•</span><p id="p0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SVR:</span> sustained virologic response.</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">•</span><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">UMCU:</span> University Medical Center Utrecht.</p></li></ul></p></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Conflict of Interest</span><p id="p0140" class="elsevierStylePara elsevierViewall">A.M. Newsum was financially supported by the “Aids Fonds” Netherlands (grant number 2013.037). C.K.Y. Ho was financially supported by the Virgo consortium, funded by the Dutch government project number FES0908, and by the Netherlands Genomics Initiative (NGI) project number 050-060-452. J.E. Arends served as an advisory board member or a speaker for Viiv, Janssen, Gilead, MSD, Abbvie and Bristol-Myers Squibb. A.I.M. Hoepelman served as an advisory board member for Gilead, Janssen, ViiV and MSD. A.M.J. Wensing has received an unrestricted grant from Janssen for this work. A.M.J. Wensing also received consultancy fees, travel and/or research grants from Bristol-Myers Squibb, Gilead, Janssen, MSD, Viiv Healthcare and Virology Education, all paid to her institution: these were not related to this work. K.J. van Erpecum has served as an advisory board member or lecturer for Abbvie, Bristol-Myers Squibb, Gilead Sciences and Janssen-Cilag (all paid to the institution). He also received grants from Janssen-Cilag and Gilead for patient support during “all oral” HCV therapy. G.J. Boland has received consultancy fees from AbbVie, paid to the institution. All other authors declare no conflict of interests.</p></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Financial Support</span><p id="p0145" class="elsevierStylePara elsevierViewall">Determination of resistance-associated polymorphisms in the University Medical Center Utrecht and the Academic Medical Center was made possible by financial support from Janssen Pharmaceuticals, Inc.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1197986" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1116632" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Patients and samples" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Sequencing procedure" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Statistical analyses" ] ] ] 4 => array:3 [ "identificador" => "s0030" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "s0035" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "s0040" "titulo" => "RAVs in the study population" ] 2 => array:2 [ "identificador" => "s0045" "titulo" => "RAVs in HIV infected vs. HIV uninfected groups" ] 3 => array:2 [ "identificador" => "s0050" "titulo" => "RAVs distribution among HCV transmission modes" ] 4 => array:2 [ "identificador" => "s0055" "titulo" => "RAVs in clade I vs. clade II viruses" ] ] ] 5 => array:2 [ "identificador" => "s0060" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "s0065" "titulo" => "Abbreviations" ] 7 => array:2 [ "identificador" => "s0070" "titulo" => "Conflict of Interest" ] 8 => array:2 [ "identificador" => "s0075" "titulo" => "Financial Support" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-11-20" "fechaAceptado" => "2016-02-21" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1116632" "palabras" => array:5 [ 0 => "Hepatitis C virus" 1 => "HIV" 2 => "Genotype 1a" 3 => "Q80K" 4 => "Drug resistance" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Background and aim.</span> Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection.</p><p id="sp1040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods.</span> HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients.</p><p id="sp2040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results.</span> 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% <span class="elsevierStyleItalic">vs.</span> 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% <span class="elsevierStyleItalic">vs.</span> 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% <span class="elsevierStyleItalic">vs.</span> 16%, p = 0.002) and N174G/N/S (10% <span class="elsevierStyleItalic">vs.</span> 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% <span class="elsevierStyleItalic">vs.</span> 22%, p=0.001) and N174 (13% <span class="elsevierStyleItalic">vs.</span> 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses.</p><p id="sp4040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusions.</span> In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.</p></span>" ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 762 "Ancho" => 1043 "Tamanyo" => 55475 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">A. Frequency of NS3 resistance-associated variants in HCV genotype 1a patients with and without HIV. Closed bars represent HIV-infected subjects and open bars represent HIV-uninfected subjects. HIV: human immunodeficiency virus. <span class="elsevierStyleBold">B.</span> Distribution of NS3 resistance-associated variants in hepatitis C genotype 1a clade I and clade II viruses. Closed bars represent clade I in HIV-infected subjects, open bars represent clade I in HIV-uninfected subjects, black/grey checkered bars represent clade II in HIV-infected subjects and white/grey checkered bars represent clade II in HIV-uninfected subjects. HIV: human immunodeficiency virus.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 306 "Ancho" => 488 "Tamanyo" => 11636 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Number of NS3 resistance-associated variants in the HIV-infected and HIV-uninfected study population. Number of RAVs per subject with interquartile range: 1 (0-1) for HIV-infected vs.1 (1-2) for HIV-uninfected. Black dots represent HIV-infected and open dots represent HIV-uninfected subjects. HIV: human immunodeficiency virus. no: number. RAVs: resistance-associated variants.</p>" ] ] 2 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study specifics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Previous treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Q80K HIV <span class="elsevierStyleItalic">vs.</span> non-HIV \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Other RAVs HIV <span class="elsevierStyleItalic">vs.</span> non-HIV \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No. of RAVs \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vicenti, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> 2012, Italy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Archived samples; genotype 1 a and 1 b;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> whole NS3 genome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2007-2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 50 HIV n = 17 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naïve to Pls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6/50 (12%) <span class="elsevierStyleItalic">vs.</span> 5/19 (29%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36L: 2/50 (4%) <span class="elsevierStyleItalic">vs.</span> 2/17 (12%); T54S: 1/50 (2%) <span class="elsevierStyleItalic">vs.</span> 1/17 (6%); V55A: 1/50 (2%) <span class="elsevierStyleItalic">vs.</span> 0/17 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At least one RAV: 10/50 (20%) <span class="elsevierStyleItalic">vs.</span> 7/17 (41%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ehret, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> 2014, Germany \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CS; all genotype 1a; NS3 amino acids 1-181 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 23 HIV n = 19 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8/19 (42%) <span class="elsevierStyleItalic">vs.</span> 9/23 (39%), p = NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Jabara, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> 2014, USA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Archived samples; all genotype 1a; NS3 amino acids 36-173 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2000-2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 20 HIV n = 20 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naïve to all anti-HCV therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6/20 (30%) <span class="elsevierStyleItalic">vs.</span> 11 /20 (55%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36ALM 38% <span class="elsevierStyleItalic">vs.;</span> 64% Q41 R 24% <span class="elsevierStyleItalic">vs.</span> 4%; T54AS 24% <span class="elsevierStyleItalic">vs.</span> 29%; V55AI 16% <span class="elsevierStyleItalic">vs.</span> 29% V107I 80% <span class="elsevierStyleItalic">vs.</span> 58%; A156SVD 22% <span class="elsevierStyleItalic">vs.</span> 16%; V/I170T 44% <span class="elsevierStyleItalic">vs.</span> 31% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overall non-Q80K RAV cumulative frequency: 0.53% <span class="elsevierStyleItalic">vs.</span> 0.37%, p = NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lin, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> 2014, USA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Archived samples; genotype 1a, 1b, 2, 4;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> 10 NS3 sites covering V36-V170, \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1998-2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 26 HIV n = 39 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naïve to Pls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36L, Q80K and R155K: 11/26 (42%) <span class="elsevierStyleItalic">vs.</span> 16/39 (41%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Beloukas, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> 2015, UK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Archived samples, genotype 1a, NS3 amino acids 1-181 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2006-2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 61 HIV n = 107 non-HIV<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naïve to all anti-HCV therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7/61 (12%) <span class="elsevierStyleItalic">vs.</span> 18/107 (17%), p = 0.379 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36LM, T54S, V55A, Q80KL, D168E, V/I170AT and N174S: 169/238<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> (63%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Applegate, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> 2015, Australia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Archived samples of a PS, genotype 1a, 11 NS3 sites covering V36-V170, NS5A, NS5B<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2004-2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 24 HIV n = 26 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naïve to Pls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2/24 (8%) <span class="elsevierStyleItalic">vs.</span> 0/26 (0%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36M: 1/24 (4%) <span class="elsevierStyleItalic">vs.</span> 0/26 (0%); V55A: 0/24 (0%) <span class="elsevierStyleItalic">vs.</span> 2/26 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median no. Of RAVs/subject: 6; Proportion subjects with 6 or more RAVs: 42% <span class="elsevierStyleItalic">vs.</span> 52%, p = 0.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">McCormick, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> 2015, UK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CS, genotype 1a, 1b, 3 and 4,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> NS3 amino acids 1-181, NS5A. NS5B<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 57 HIV n = 23 non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27/57 HIV group Experienced with PEG-IFN/RBV Unknown for non-HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5/57 (9%) <span class="elsevierStyleItalic">vs.</span> 8/23 (35%), p = NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T54ST: 0/57 (0%) <span class="elsevierStyleItalic">vs.</span> 2/23 (9%); V36L: 0/57 (0%) <span class="elsevierStyleItalic">vs.</span> 1/23 (4%); R155K: 0/57 (0%) <span class="elsevierStyleItalic">vs.</span> 1/23 (4%); \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At least one RAV: 5/57 (9%) <span class="elsevierStyleItalic">vs.</span> 11/23 (48%), p < 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045899.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Abstracts or full articles from original studies found through a systematic search of the literature in the electronic database PubMed, conducted on August 4, 2015, with the following search terms used: “HIV” and synonyms combined with “hepatitis C” and synonyms combined with “NS3” and synonyms. Studies without genotype la NS3 RAV data in HIV <span class="elsevierStyleItalic">vs.</span> non-HIV infected subjects were excluded.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Only genotype la data is given in the table.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Only NS3 data is given in the table.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Specific data only given in subgroup of 168 patients, with total study population consisting of 238 subjects. CS: cross-sectional study. RAV: resistance-associated variant. NA: not available. NS: not significant. PI: protease inhibitor. PS: prospective study.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Overview of published studies on distribution of NS3 resistance-associated variants in HCV genotype 1a patients with and without HIV.</p>" ] ] 3 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">Data are presented as median (range) or n (%).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All patients<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> n = 148 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HIV-infected n = 68 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HIV-uninfected n = 80 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (yrs.) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (22-74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 (22-67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 (23-74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male gender<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">118/129(92%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68/68 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50/61 (82%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mode of HCV transmission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Injection drug use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/148 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/68 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24/80 (30%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood products \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14/148 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/68 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/80 (13%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MSM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58/148 (39%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58/68 (85%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/80 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8/148 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/68 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7/80 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43/148 (29%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/68 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39/80 (49%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment naïve \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">124/148(84%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61/68 (90%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63/80 (79%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN mono therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2/148 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/68 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2/80 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PEG-IFN/RBV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22/148 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7/68 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/80 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT (U/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (17-2384) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">124 (17-2384) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (18-331) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilirubin (μmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (3-159) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (3-159) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (3-33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cirrhosis<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/123 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6/65 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19/58 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCV RNA (Log<span class="elsevierStyleInf">10</span> IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3 (3.1-9.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3 (3.1-8.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 (3.8-9.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative HIV RNA<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42/67 (63%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42/67 (63%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4 count<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">c</span></a> ≥ 350 cells/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51/65 (79%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51/65 (79%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">cART<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50/65 (77%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50/65 (77%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive HBsAg<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/119 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3/66 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/53 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045902.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Data incomplete in 19 patients.</p>" ] 1 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Data known in 123 patients. <a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a>HIV RNA < 50 copies/mL.</p>" ] 2 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Data unknown in 1 respectively 3 patients.</p>" ] 3 => array:3 [ "identificador" => "tblfn0040" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Data unknown in 29 patients. ALT: alanine aminotransferase. cART: combined antiretroviral treatment HBsAg: hepatitis b surface antigen. HCV: hepatitis C virus. HIV: human immunodeficiency virus. IFN: interferon. NA: not applicable. PEG-IFN: pegylated interferon. RBV: ribavirin. yrs: years.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of hepatitis C genotype 1a patients infected with and without HIV.</p>" ] ] 4 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0010" class="elsevierStyleSimplePara elsevierViewall">Data are presented as n (%). Data on F43, R109, V132, S138, R155, A156, V158, D168 and L/M175 polymorphisms prevalence are not given as they did not occur in the study population.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All patients n = 148 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HIV-infected n = 68 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HIV-uninfected n = 80 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q41H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T54ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V55AI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q80K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (36%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (24%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V107GI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">S122DGNS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (16%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A156V \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V/I170VT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N174GNS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 (35%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (55%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045903.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Distribution of resistance-associated variants in 148 NS3/4A protease inhibitor treatment-naïve patients with and without HIV infection.</p>" ] ] 5 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0015" class="elsevierStyleSimplePara elsevierViewall">Data are presented as n (%). Data on F43, R109, V132, S138, R155, A156, V158, D168 and L/M175 polymorphisms prevalence are not given as they did not occur in the study population. MSM: men who have sex with men.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MSM n = 58 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Injection drugs n = 25 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transfusion n = 14 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Other/Unknown n = 51 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q41H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T54ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V55AI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q80K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (16%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (43%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V107GI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">S122DGNS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (12%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A156V \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V/I170VT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N174GNS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (40%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (43%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (57%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045900.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Distribution of resistance-associated variants in 148 NS3/4A protease inhibitor treatment-naïve patients according to modes of HCV transmission.</p>" ] ] 6 => array:7 [ "identificador" => "t0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0020" class="elsevierStyleSimplePara elsevierViewall">Data are presented as n (%). Data on F43, R109, V132, S138, R155, A156, V158, D168 and L/M175 polymorphisms prevalence are not given as they did not occur in the study population.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clade I n = 97 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clade II n = 51 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V36L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q41H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T54ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V55AI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Q80K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (55%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V107GI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">S122DGNS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A156V \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in phase IIb/III studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Lenz O." 1 => "Verbinnen T." 2 => "Fevery B." 3 => "Tambuyzer L." 4 => "Vijgen L." 5 => "Peeters M." 6 => "Buelens A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2014.11.032" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2014" "volumen" => "62" "paginaInicial" => "1008" "paginaFinal" => "1014" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25445400" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534715036484" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic issues in HIV/HCV-coinfected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Sulkowski M." 1 => "Benhamou Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2006.00816.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2007" "volumen" => "14" "paginaInicial" => "371" "paginaFinal" => "386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17501757" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Soriano V." 1 => "Perelson A.S." 2 => "Zoulim F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jac/dkn175" "Revista" => array:6 [ "tituloSerie" => "J Antimicrob Chemother" "fecha" => "2008" "volumen" => "62" "paginaInicial" => "1" "paginaFinal" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18441341" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients in the european region" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Sarrazin C." 1 => "Lathouwers E." 2 => "Peeters M." 3 => "Daems B." 4 => "Buelens A." 5 => "Witek J." 6 => "Wyckmans Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.antiviral.2015.01.003" "Revista" => array:6 [ "tituloSerie" => "Antiviral Res" "fecha" => "2015" "volumen" => "116" "paginaInicial" => "10" "paginaFinal" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25614456" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global distribution and prevalence of hepatitis C virus genotypes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Messina J.P." 1 => "Humphreys I." 2 => "Flaxman A." 3 => "Brown A." 4 => "Cooke G.S." 5 => "Pybus O.G." 6 => "Barnes E." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.27259" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2015" "volumen" => "61" "paginaInicial" => "77" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25069599" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence for separation of HCV subtype 1a into two distinct clades" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Pickett B.E." 1 => "Striker R." 2 => "Lefkowitz E.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2010.01342.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2011" "volumen" => "18" "paginaInicial" => "608" "paginaFinal" => "618" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20565573" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Two distinct hepatitis C virus genotype 1a clades have different geographical distribution and association with natural resistance to NS3 protease inhibitors 2015" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "De Luca A." 1 => "Di Giambenedetto S." 2 => "Presti A.L." 3 => "Sierra S." 4 => "Prosperi M." 5 => "Cella E." 6 => "Giovanetti M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ofid/ofv043" "Revista" => array:5 [ "tituloSerie" => "Open Forum Infect Dis" "fecha" => "2015" "volumen" => "2" "paginaInicial" => "ofv043" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26213689" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Susceptibility of treatment-naive hepatitis C virus (HCV) clinical isolates to HCV protease inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Bae A." 1 => "Sun S.C." 2 => "Qi X." 3 => "Chen X." 4 => "Ku K." 5 => "Worth A." 6 => "Wong K.A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.00777-10" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2010" "volumen" => "54" "paginaInicial" => "5288" "paginaFinal" => "5297" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20855726" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ultratiefe pyrosequenz-analyse (UDPS) von neu beschriebenen seltenen resistenzvarianten der hepatitis C virus NS3 protease bei patienten, die mit telaprevir oder boceprevir behandelt wurden" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Susser S." 1 => "Schelhorn S." 2 => "Lange C." 3 => "Welsch C." 4 => "Vermehren J." 5 => "Perner D." 6 => "Füller C." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Z Gastroenterol" "fecha" => "2012" "volumen" => "50" "paginaInicial" => "K052" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resistance to hepatitis C virus protease inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Kieffer T.L." 1 => "George S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.coviro.2014.04.008" "Revista" => array:6 [ "tituloSerie" => "Current opinion in virology" "fecha" => "2014" "volumen" => "8" "paginaInicial" => "16" "paginaFinal" => "21" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24852142" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: The COSMOS randomised study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Lawitz E." 1 => "Sulkowski M.S." 2 => "Ghalib R." 3 => "Rodriguez-Torres M." 4 => "Younossi Z.M." 5 => "Corregidor A." 6 => "DeJesus E." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "The Lancet" "fecha" => "2014" "volumen" => "384" "paginaInicial" => "1756" "paginaFinal" => "1765" "itemHostRev" => array:3 [ "pii" => "S0022534715046133" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Grazoprevir/elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Forns X." 1 => "Gordon S.C." 2 => "Zuckerman E." 3 => "Lawitz E." 4 => "Calleja J.L." 5 => "Hofer H." 6 => "Gilbert C." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2015.04.009" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "63" "paginaInicial" => "564" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25895428" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deconvoluting the composition of low-frequency hepatitis C viral quasispecies: Comparison of genotypes and NS3 resistance-associated variants between HCV/HIV coinfected hemophiliacs and HCV monoinfected patients in japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Ogishi M." 1 => "Yotsuyanagi H." 2 => "Tsutsumi T." 3 => "Gatanaga H." 4 => "Ode H." 5 => "Sugiura W." 6 => "Moriya K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0119145" "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0119145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25748426" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Appearance of NS3 Q80K mutation in HCV genotype 1a monoor HIV/HCV co-infected patients in a berlin laboratory" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Ehret R." 1 => "Neifer S." 2 => "Walter H." 3 => "Baumgarten A." 4 => "Obermeier M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7448/IAS.17.4.19741" "Revista" => array:6 [ "tituloSerie" => "J Int AIDS Soc" "fecha" => "2014" "volumen" => "17" "numero" => "4, Suppl. 3" "paginaInicial" => "19741" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25397486" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in italy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Vicenti I." 1 => "Rosi A." 2 => "Saladini F." 3 => "Meini G." 4 => "Pippi F." 5 => "Rossetti B." 6 => "Sidella L." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jac/dkr581" "Revista" => array:6 [ "tituloSerie" => "J Antimicrob Chemother" "fecha" => "2012" "volumen" => "67" "paginaInicial" => "984" "paginaFinal" => "987" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22258932" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "No beneficial effects of amantadine in treatment of chronic hepatitis C patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "van Soest H." 1 => "van der Schaar P.J." 2 => "Koek G.H." 3 => "de Vries R.A." 4 => "van Ooteghem N.A." 5 => "van Hoek B." 6 => "Drenth J.P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.dld.2009.10.006" "Revista" => array:6 [ "tituloSerie" => "Dig Liver Dis" "fecha" => "2010" "volumen" => "42" "paginaInicial" => "496" "paginaFinal" => "502" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20018575" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on hepatitis C virus resistance to directacting antiviral agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Poveda E." 1 => "Wyles D.L." 2 => "Mena Á" 3 => "Pedreira J.D." 4 => "Castro-Iglesias Á" 5 => "Cachay E." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.antiviral.2014.05.015" "Revista" => array:6 [ "tituloSerie" => "Antiviral Res" "fecha" => "2014" "volumen" => "108" "paginaInicial" => "181" "paginaFinal" => "191" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24911972" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Nevot M." 1 => "Boesecke C." 2 => "Parera M." 3 => "Andrés C." 4 => "Franco S." 5 => "Revollo B." 6 => "Ingiliz P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jvh.12254" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2014" "volumen" => "21" "paginaInicial" => "e19" "paginaFinal" => "e28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24674023" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "van de Laar T." 1 => "Pybus O." 2 => "Bruisten S." 3 => "Brown D." 4 => "Nelson M." 5 => "Bhagani S." 6 => "Vogel M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2009" "volumen" => "136" "paginaInicial" => "1609" "paginaFinal" => "1617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19422083" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increase in HCV incidence among men who have sex with men in amsterdam most likely caused by sexual transmission" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "van de Laar T.J." 1 => "van der Bij A.K." 2 => "Prins M." 3 => "Bruisten S.M." 4 => "Brinkman K." 5 => "Ruys T.A." 6 => "van der Meer J.T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/518796" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2007" "volumen" => "196" "paginaInicial" => "230" "paginaFinal" => "238" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17570110" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Bagaglio S, Uberti-Foppa C, Messina E, Merli M, Hasson H, Andolina A, Galli A, et al. Distribution of natural resistance to NS3 protease inhibitors in hepatitis C genotype 1a separated into clades 1 and 2 and in genotype 1b of HIV infected patients. <span class="elsevierStyleItalic">Clin Microbiol Infect</span> 2015; S1198-743X(15)01033-2." ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL recommendations on treatment of hepatitis C 2015. <span class="elsevierStyleItalic">J Hepatol</span> 2015." ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a scottish cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Shepherd S.J." 1 => "Abdelrahman T." 2 => "MacLean A.R." 3 => "Thomson E.C." 4 => "Aitken C." 5 => "Gunson R.N." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2015.02.005" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2015" "volumen" => "65" "paginaInicial" => "50" "paginaFinal" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25766988" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus (HCV) NS3 sequence diversity and antiviral resistance-associated variant frequency in HCV/HIV coinfection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Jabara C.B." 1 => "Hu F." 2 => "Mollan K.R." 3 => "Williford S.E." 4 => "Menezes P." 5 => "Yang Y." 6 => "Eron J.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.03466-14" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2014" "volumen" => "58" "paginaInicial" => "6079" "paginaFinal" => "6092" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25092699" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus NS3 mutations in haemophiliacs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Lin M." 1 => "Charlton A." 2 => "Rouster S." 3 => "Zamor P." 4 => "Sherman K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hae.12420" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2014" "volumen" => "20" "paginaInicial" => "659" "paginaFinal" => "665" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24697920" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Beloukas A, King S, Childs K, Papadimitropoulos A, Hopkins M, Atkins M, Agarwal K, et al. Detection of the NS3 Q80K polymorphism by sanger and deep sequencing in hepatitis C virus (HCV) genotype 1a strains in the united kingdom. <span class="elsevierStyleItalic">Clinical Microbiology and Infection</span> 2015; pii: S1198-743X(15)00734-X." ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Applegate T.L." 1 => "Gaudieri S." 2 => "Plauzolles A." 3 => "Chopra A." 4 => "Grebely J." 5 => "Lucas M." 6 => "Hellard M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3851/IMP2821" "Revista" => array:6 [ "tituloSerie" => "Antivir Ther" "fecha" => "2015" "volumen" => "20" "paginaInicial" => "199" "paginaFinal" => "208" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25105742" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Baseline drug resistance mutations are detectable in HCV genes NS3 and NS5A but not NS5B in acute and chronic HIV-coinfected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "McCormick A.L." 1 => "Moynihan L." 2 => "Macartney M.J." 3 => "Garcia-Diaz A." 4 => "Smith C." 5 => "Johnson M.A." 6 => "Rodger A.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3851/IMP2871" "Revista" => array:6 [ "tituloSerie" => "Antivir Ther" "fecha" => "2015" "volumen" => "20" "paginaInicial" => "361" "paginaFinal" => "363" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25279548" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus treatment in the real world: Optimising treatment and access to therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Zoulim F." 1 => "Liang T.J." 2 => "Gerbes A.L." 3 => "Aghemo A." 4 => "Deuffic-Burban S." 5 => "Dusheiko G." 6 => "Fried M.W." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2015-310421" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2015" "volumen" => "64" "paginaInicial" => "1824" "paginaFinal" => "1833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26449729" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C 2015." ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consideration of viral resistance for optimization of direct antiviral therapy of hepatitis C virus genotype 1-infected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Dietz J." 1 => "Susser S." 2 => "Berkowski C." 3 => "Perner D." 4 => "Zeuzem S." 5 => "Sarrazin C." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0134395" "Revista" => array:5 [ "tituloSerie" => "PloS one" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0134395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26317755" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Tan S, He Y. Hepatitis C: Antiviral drug discovery and development. Horizon Scientific Press; 2011." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001500000005/v1_201905310950/S1665268119306313/v1_201905310950/en/main.assets" "Apartado" => array:4 [ "identificador" => "77721" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001500000005/v1_201905310950/S1665268119306313/v1_201905310950/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119306313?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 1 | 2 |
| 2024 October | 11 | 0 | 11 |
| 2024 September | 11 | 1 | 12 |
| 2024 August | 17 | 3 | 20 |
| 2024 July | 12 | 3 | 15 |
| 2024 June | 8 | 1 | 9 |
| 2024 May | 10 | 6 | 16 |
| 2024 April | 7 | 4 | 11 |
| 2024 March | 11 | 3 | 14 |
| 2024 February | 5 | 7 | 12 |
| 2024 January | 8 | 4 | 12 |
| 2023 December | 5 | 6 | 11 |
| 2023 November | 8 | 1 | 9 |
| 2023 October | 9 | 3 | 12 |
| 2023 September | 7 | 2 | 9 |
| 2023 August | 3 | 3 | 6 |
| 2023 July | 4 | 1 | 5 |
| 2023 June | 8 | 5 | 13 |
| 2023 May | 4 | 1 | 5 |
| 2023 April | 6 | 1 | 7 |
| 2023 March | 10 | 2 | 12 |
| 2023 February | 4 | 3 | 7 |
| 2023 January | 6 | 3 | 9 |
| 2022 December | 4 | 4 | 8 |
| 2022 November | 9 | 2 | 11 |
| 2022 October | 7 | 6 | 13 |
| 2022 September | 8 | 4 | 12 |
| 2022 August | 11 | 5 | 16 |
| 2022 July | 12 | 7 | 19 |
| 2022 June | 5 | 4 | 9 |
| 2022 May | 4 | 6 | 10 |
| 2022 April | 9 | 6 | 15 |
| 2022 March | 13 | 7 | 20 |
| 2022 February | 9 | 3 | 12 |
| 2022 January | 15 | 3 | 18 |
| 2021 December | 5 | 7 | 12 |
| 2021 November | 6 | 7 | 13 |
| 2021 October | 17 | 9 | 26 |
| 2021 September | 4 | 8 | 12 |
| 2021 August | 6 | 6 | 12 |
| 2021 July | 5 | 14 | 19 |
| 2021 June | 12 | 3 | 15 |
| 2021 May | 6 | 6 | 12 |
| 2021 April | 39 | 6 | 45 |
| 2021 March | 9 | 7 | 16 |
| 2021 February | 4 | 4 | 8 |
| 2021 January | 3 | 7 | 10 |
| 2020 December | 9 | 5 | 14 |
| 2020 November | 7 | 5 | 12 |
| 2020 October | 6 | 10 | 16 |
| 2020 September | 10 | 6 | 16 |
| 2020 August | 8 | 7 | 15 |
| 2020 July | 7 | 4 | 11 |
| 2020 June | 1 | 3 | 4 |
| 2020 May | 11 | 4 | 15 |
| 2020 April | 4 | 1 | 5 |
| 2020 March | 1 | 3 | 4 |
| 2020 February | 8 | 5 | 13 |
| 2020 January | 7 | 3 | 10 |
| 2019 December | 7 | 10 | 17 |
| 2019 November | 7 | 5 | 12 |
| 2019 October | 1 | 2 | 3 |
| 2019 September | 2 | 1 | 3 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 3 | 8 | 11 |
| 2019 June | 5 | 8 | 13 |
| 2019 May | 1 | 4 | 5 |
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