Bienvenido a EMEI

Esta web ha sido acreditada por distintos organismos y fundaciones. Dicha acreditación sirve como garantía de que este sitio web, en la fecha de su certificación, cumple con unos requisitos mínimos que garantizan la fiabilidad y credibilidad de la información científica, médica y de salud que muestra.

EMEI- Últimos artículos científicos publicados:

• PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV coinfected patients under HCV therapy. -

  PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV coinfected patients under HCV therapy.

  J Acquir Immune Defic Syndr. 2014 Jul 26;

  Authors: Fernández-Rodríguez A, Berenguer J, Rallón N, Jiménez-Sousa MA, López JC, Soriano V, García-Álvarez M, Cosín J, Martínez P, Guzmán-Fulgencio M, Miralles P, Benito JM, Resino S

  Abstract
  OBJECTIVES:: To analyze whether peroxisome proliferator-activated receptor gamma (PPAR[Latin Small Letter Gamma]2) rs1801282 (Pro12Ala) polymorphism is associated with the response to peg-interferon-alpha plus ribavirin treatment in human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) coinfected patients, and whether it is able to predict the outcome of HCV treatment.
  DESIGN:: Retrospective follow-up study.
  METHODS:: 285 naïve patients, who started HCV-treatment, were genotyped for PPARγ2 and IL28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.
  RESULTS:: The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 (adjusted odds ratio (aOR)= 7.66 (95% of confidence interval (95%CI)= 3.96; 14.81) p<0.001), HCV-viremia <500,000 IU/mL (aOR= 2.20 (95%CI= 1.16; 4.15) p=0.015), no/mild liver fibrosis (F<2) (aOR= 1.92 (95%CI= 1.08; 3.42) p=0.026), IL28B rs12980275 AA genotype (aOR= 2.70 (95%CI= 1.54; 4.71) p<0.001), and PPARγ2 rs1801282 CG/GG genotype (aOR= 2.93 (95%CI= 1.27; 6.72) p=0.011). When PPARγ2 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves (AUROC) was 0.766±0.028.
  CONCLUSIONS:: The presence of PPARγ2 rs1801282 CG/GG genotype (Ala variant) was associated with increased odds for achieving SVR in HIV/HCV coinfected patients on HCV treatment.
  

  PMID: 25072612 [PubMed - as supplied by publisher]

• Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery. -

  Related Articles

  Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery.

  J Infect. 2014 Jul 17;

  Authors: Jiménez-Sousa MA, Tamayo E, Guzmán-Fulgencio M, Heredia M, Fernández-Rodríguez A, Gómez E, Almansa R, Gómez-Herreras JI, García-Álvarez M, Gutiérrez-Junco S, Bermejo-Martin JF, Resino S, the Spanish Sepsis Group (SpSG)

  Abstract
  OBJECTIVE: To analyse whether mitochondrial DNA (mtDNA) haplogroups are associated with severe sepsis and mortality after major surgery.
  METHODS: We performed a case-control study on 240 cardiac or abdominal surgery patients developing severe sepsis (Case-group) and 267 cardiac or abdominal surgery patients without severe sepsis and with systemic inflammatory response syndrome (SIRS, Control-group). Furthermore, a longitudinal substudy was performed for analysing the survival in septic patients. Only European white patients within the N macro-cluster were included.
  RESULTS: Case-group underwent cardiac surgery had lower frequencies of cluster HV (p = 0.005) and haplogroup H (p = 0.005) and higher frequencies of cluster JT (p = 0.028) than Control-group; but no significant differences were found for abdominal surgery. Besides, both cluster HV and haplogroup H were associated with decreased odds of severe sepsis (odds ratio (aOR) = 0.45 (95%CI = 0.25; 0.82); p = 0.009) and aOR = 0.48 (95%CI = 0.26; 0.87); p = 0.015), respectively) among patients underwent cardiac surgery. In Case-group, 45.4% (109/240) patients died with a survival median of 39 (95%CI = 31.4; 46.62) days. When the clusters were examined, 41% (55/134) patients within cluster HV died versus 71.4% (10/14) patients within cluster IWX (p = 0.018). Additionally, patients within cluster IWX had an increased risk of death (adjusted hazard ratio (aHR) = 2.22; (95%CI = 1.14; 4.34); p = 0.019).
  CONCLUSIONS: European mitochondrial haplogroups might be related to the onset of severe sepsis in patients who underwent major cardiac surgery, but not in patients underwent major abdominal surgery. Besides, mtDNA haplogroups could have influence on mortality in septic patients.
  

  PMID: 25043396 [PubMed - as supplied by publisher]

• Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis. -

  Related Articles

  Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis.

  Hepatology. 2014 Jun 27;

  Authors: García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S

  Abstract
  Background and Aims: There is growing evidence that vitamin D is related to chronic hepatitis C (CHC) pathogenicity. We analysed the relationship of vitamin D status with advanced liver fibrosis (ALF) in CHC treatment-naïve patients and sustained virologic response (SVR) in CHC patients on pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) therapy. Methods: We performed a meta-analysis of all eligible studies published to date (April, 2014) in PubMed, SCOPUS, LILACS and the Cochrane Library , assessing plasma/serum vitamin D levels related to ALF and/or SVR. Pooled odds ratios were estimated by either fixed or random effects models. Results: Fourteen studies were selected from the literature search, 7 for ALF (1083 patients) and 11 for SVR (2672 patients). For liver fibrosis, low vitamin D status was related to a diagnosis of ALF, with the cut-offs of 10 ng/mL (OR=2.37 (95%CI=1.20, 4.72)) and 30 ng/mL (OR=2.22 (95%CI=1.24, 3.97)) being significant, and a near-significance for 20 ng/mL (OR=1.44 (95%CI=0.99, 2.12)). Regarding SVR, a significant heterogeneity among studies was found (p<0.001), and we only found a significant association with SVR for a vitamin D cut-off of 20 ng/mL (OR=0.53 (95%CI=0.31, 0.91)). When meta-analysis was performed excluding the outliers, significant pooled ORs were found for all patients [10 ng/mL (OR=0.48 (95%CI=0.34, 0.67)) and 20 ng/mL (OR=0.58 (95%CI=0.45, 0.76))] and GT1/4 patients [10 ng/mL (OR=0.53 (95%CI=0.34, 0.81)) and 20 ng/mL (OR=0.54 (95%CI=0.39, 0.74))]. Conclusions: Low vitamin D status in CHC patients is associated with a higher likelihood of having ALF and lower odds of achieving SVR following pegIFNα/ribavirin therapy. (Hepatology 2014;).
  

  PMID: 24975775 [PubMed - as supplied by publisher]

• European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients. -

  Related Articles

  European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients.

  HIV Med. 2014 Aug;15(7):425-30

  Authors: Guzmán-Fulgencio M, Rallón N, Berenguer J, Fernández-Rodríguez A, Soriano V, Miralles P, Jiménez-Sousa M, Restrepo C, López J, García-Álvarez M, Aldámiz T, Benito J, Resino S

  Abstract
  OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV).
  METHODS: We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data.
  RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype.
  CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.
  

  PMID: 24580757 [PubMed - in process]

• Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients. -

  Related Articles

  Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients.

  Eur J Clin Invest. 2014 May;44(5):453-62

  Authors: Pineda-Tenor D, Berenguer J, García-Broncano P, Jiménez-Sousa MA, Fernández-Rodríguez A, Diez C, García-Álvarez M, Carrero A, Catalán P, Aldámiz-Echevarria T, Resino S

  Abstract
  BACKGROUND: The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients.
  METHODS: We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL and HOMA≥3·8) according to ADIPOQ genotype under a dominant inheritance model.
  RESULTS: Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P=0·038) and percentages of TC≥200 mg/dL (P=0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR)=0·92 [(95% CI=0·85; 0·99) P=0·024]) and low likelihood of TC≥200 mg/dL (odds ratio (OR)=0·32 [(95% CI=0·11; 0·88) P=0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR=0·89; P=0·027), LDL-C (AMR=0·85; P=0·039) and non-HDL-C (AMR=0·86; P=0·015). No significant associations were found between rs2241766 and HOMA values.
  CONCLUSIONS: The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.
  

  PMID: 24528335 [PubMed - in process]

• SLC30A8 rs13266634 polymorphism is related to a favorable cardiometabolic lipid profile in HIV/hepatitis C virus-coinfected patients. -

  Related Articles

  SLC30A8 rs13266634 polymorphism is related to a favorable cardiometabolic lipid profile in HIV/hepatitis C virus-coinfected patients.

  AIDS. 2014 Jun 1;28(9):1325-32

  Authors: Pineda-Tenor D, Micheloud D, Berenguer J, Jiménez-Sousa MA, Fernández-Rodríguez A, García-Broncano P, Guzmán-Fulgencio M, Diez C, Bellón JM, Carrero A, Aldámiz-Echevarria T, García-Álvarez M, Resino S

  Abstract
  OBJECTIVE: To analyze the relationship of SLC30A8 rs13266634 polymorphism with insulin resistance and dyslipidemia in HIV/hepatitis C virus (HCV)-coinfected patients.
  DESIGN: Cross-sectional study in 260 HIV/HVC-coinfected patients.
  METHODS: SLC30A8 polymorphisms were genotyped by GoldenGate assay. Genetic data were analyzed under the dominant inheritance model (CT/TT versus CC). Cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, atherogenic index, and homeostatic model assessment of insulin resistance (HOMA-IR) values were assayed for each genotype.
  RESULTS: rs13266634 CT/TT carriers had higher serum values of HDL-C (P = 0.014) and lower values of LDL-C/HDL-C (P = 0.036) and atherogenic index (P = 0.011) than CC carriers. Additionally, rs13266634 CT/TT carriers had lower percentage of HDL 35 mg/dl or less (P = 0.050) and higher percentage of LDL/HDL at least 3 (P = 0.091) and atherogenic index at least 3.5 (P = 0.003) than CC carriers. When adjusted regression analysis was performed, rs13266634 CT/TT genotype was associated with high serum values of HDL-C [arithmetic mean ratio (AMR) = 1.10 (95% confidence interval, CI = 1.03-1.19) P = 0.006], and low values of LDL-C/HDL-C [AMR = 0.88 (95% CI = 0.79-0.99) P = 0.045] and atherogenic index [AMR = 0.89 (95% CI = 0.81-0.98) P = 0.024]. For categorical outcomes, rs13266634 CT/TT carriers had lower significant likelihood of having atherogenic index at least 3.5 [odds ratio = 0.47 (95% CI = 0.26-0.83) P = 0.009], and very close to significance for LDL-C/HDL-C at least 3 [odds ratio = 0.52 (95% CI = 0.27-1.02) P = 0.056], supporting the protective effect of the CT/TT genotypes. No significant relationship was observed between rs13266634 and HOMA-IR values.
  CONCLUSION: rs13266634 CT/TT genotype was associated to higher levels of HDL-C and lower values of cardiovascular risk indices (LDL-C/HDL-C and atherogenic index), but there was a lack of association with HOMA-IR values. Thus, rs13266634 polymorphism might play a significant role in lipid metabolism and cardiovascular risk in HIV/HCV-coinfected patients.
  

  PMID: 24499956 [PubMed - in process]

• IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients. -

  Related Articles

  IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

  J Viral Hepat. 2014 Mar;21(3):189-97

  Authors: Jiménez-Sousa MA, Berenguer J, Fernández-Rodríguez A, Micheloud D, Guzmán-Fulgencio M, Miralles P, Pineda-Tenor D, García-Álvarez M, López JC, Aldámiz-Echevarria T, Carrero A, Resino S

  Abstract
  Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.
  

  PMID: 24438680 [PubMed - in process]

• Incidence and mortality of tuberculosis disease in Spain between 1997 and 2010: impact of human immunodeficiency virus (HIV) status. -

  Related Articles

  Incidence and mortality of tuberculosis disease in Spain between 1997 and 2010: impact of human immunodeficiency virus (HIV) status.

  J Infect. 2014 Apr;68(4):355-62

  Authors: Alvaro-Meca A, Rodríguez-Gijón L, Díaz A, Gil A, Resino S

  Abstract
  OBJECTIVE: To estimate incidence and mortality of TB disease in Spain, as well as TB recurrence and its mortality, and to analyse its trend from 1997 to 2010 in human immunodeficiency virus (HIV)-infected patients (HIV(+) group), compared to HIV-uninfected subjects (HIV(-) group).
  METHODS: We performed a retrospective study using data from Minimum Basic Data Set. The outcome variables were new TB diagnosis, TB recurrences, and mortality; which were analysed through three calendar periods related to widespread use of combination antiretroviral therapy (cART): a) From 1997 to 1999 for early-period cART; b) from 2000 to 2003 for mid-period cART; and c) from 2004 to 2008 for late-period cART.
  RESULTS: We studied 86,093 HIV-uninfected patients and 17,031 HIV infected patients. TB diagnosis in HIV(-) group (events per 100,000 patients-yr) decreased from 20.16 (1997-1999) to 16.31 (2000-2003; p < 0.001), and later to 13.48 (2004-2010; p < 0.001); and among HIV(+) group (events per 1000 patients-yr) it decreased from 19.23 (1997-1999) to 10.93 (2000-2003; p < 0.001), and later to 6.35 (2004-2010; p < 0.001). For the mortality, HIV(-) group (events per 1,000,000 patients-yr) decreased from 11.5 (1997-1999) to 9.8 (2000-2003; p < 0.001), and later to 7.2 (2004-2010; p < 0.001); and HIV(+) group (events per 10,000 patients-yr) decreased from 20.69 (1997-1999) to 13.20 (2000-2003; p < 0.001), and later to 6.83 (2004-2010; p < 0.001). During the whole period, the diagnostic rate and mortality of TB remained 100-fold higher in HIV(+) group than HIV(-) group (p < 0.001). Moreover, HIV (+) group had higher percentage of patients with TB recurrence than HIV(-) group (p < 0.001).
  CONCLUSION: TB diagnosis and mortality decreased in Spain between 1997 and 2010, in both HIV infected patients and people without HIV infection; but these rates remained higher in HIV infected patients.
  

  PMID: 24365787 [PubMed - in process]

• Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients. -

  Related Articles

  Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients.

  J Infect. 2014 Feb;68(2):176-84

  Authors: Guzmán-Fulgencio M, García-Álvarez M, Berenguer J, Jiménez-Sousa MÁ, Cosín J, Pineda-Tenor D, Carrero A, Aldámiz T, Alvarez E, López JC, Resino S

  Abstract
  OBJECTIVE: To study the association of plasma 25-hydroxy vitamin D (25(OH)D) levels in HIV/HCV coinfected patients with severity of liver disease and virological response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV).
  METHODS: A cross-sectional study in 174 HIV/HCV coinfected patients that underwent a liver biopsy previously to start HCV therapy and a retrospective study of 125 of them. Plasma 25(OH)D levels were quantified by enzyme immunoassay. Liver biopsies were evaluated by METAVIR score. A sustained virological response (SVR) was defined as an undetectable serum HCV viral load (<10 IU/mL) up through 24 weeks after the end of HCV treatment.
  RESULTS: The median of plasma 25(OH)D level was 48 nmol/L (p25th: 32.5; p75th: 56.1) and 27 (15.5%) had 25(OH)D deficiency (<25 nmol/L). The percentage of 25(OH)D deficiency was higher in patients with significant fibrosis (F ≥ 2) (92.6% vs. 57.1%; p = 0.010) and moderate necroinflammatory activity grade (A ≥ 2) (85.2% vs. 60%; p = 0.043). However, adjusted logistic regression analyses showed that 25(OH)D deficiency was only associated with severity of liver disease [F ≥ 2 (OR = 8.47 (95% of confidence interval (CI) = 1.88; 38.3); p = 0.005) and A ≥ 2 (OR = 3.25 (95%CI = 1.06; 10.1); p = 0.040)]. Moreover, any significant relationship was found between 25(OH)D deficiency and SVR after HCV therapy.
  CONCLUSION: Plasma 25(OH)D deficiency was associated with liver disease severity in HIV/HCV coinfected patients, but it was not associated with HCV treatment failure.
  

  PMID: 24184809 [PubMed - in process]

• ACSM4 polymorphisms are associated with rapid AIDS progression in HIV-infected patients. -

  Related Articles

  ACSM4 polymorphisms are associated with rapid AIDS progression in HIV-infected patients.

  J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):27-32

  Authors: Guzmán-Fulgencio M, Jiménez JL, Jiménez-Sousa MA, Bellón JM, García-Álvarez M, Soriano V, Gijón-Vidaurreta P, Bernal-Morell E, Viciana P, Muñoz-Fernández MÁ, Resino S

  Abstract
  : Our aim was to explore the association among ACSM4 and PECI polymorphisms and AIDS progression in 454 HIV-infected patients never treated with antiretroviral drugs (146 long-term nonprogressors, 228 moderate progressors, and 80 rapid progressors). For ACSM4 polymorphisms, rs7137120 AA/AG and rs7961991 CC/CT genotypes had higher odds of having a rapid AIDS progression [odds ratio (OR) = 3.21; 95% of confidence interval (95% CI) = 1.26 to 8.16; P = 0.014 and OR = 3.60; 95% CI = 1.38 to 9.36; P = 0.009, respectively]. Additionally, the ACSM4 haplotype integrated for both rs7961991 A and rs7137120 C alleles had higher odds of having a rapid AIDS progression (OR = 2.85; 95% CI = 1.28 to 6.25; P = 0.010). For PECI polymorphisms, no significant associations were found. In conclusion, ACSM4 polymorphisms might play a significant role in AIDS progression.
  

  PMID: 23982661 [PubMed - indexed for MEDLINE]

• HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy. -

  Related Articles

  HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.

  AIDS. 2013 May 15;27(8):1231-8

  Authors: Guzmán-Fulgencio M, Berenguer J, Rallón N, Fernández-Rodríguez A, Miralles P, Soriano V, Jiménez-Sousa MA, Cosín J, Medrano J, García-Álvarez M, López JC, Benito JM, Resino S

  Abstract
  OBJECTIVES: To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients.
  DESIGN: Retrospective follow-up study.
  METHODS: We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment.
  RESULTS: The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35-3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03-2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47-31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ± 0.024.
  CONCLUSION: The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.
  

  PMID: 23811951 [PubMed - indexed for MEDLINE]

• Prediction of hepatic fibrosis in patients coinfected with HIV and hepatitis C virus based on genetic markers. -

  Related Articles

  Prediction of hepatic fibrosis in patients coinfected with HIV and hepatitis C virus based on genetic markers.

  J Acquir Immune Defic Syndr. 2013 Dec 15;64(5):434-42

  Authors: Fernández-Rodríguez A, Berenguer J, Jiménez-Sousa MA, Guzmán-Fulgencio M, Micheloud D, Miralles P, López JC, Bellón JM, Aldamiz-Echevarria T, García-Broncano P, Carrero A, Alvarez E, Resino S

  Abstract
  OBJECTIVE: To assess the ability of the cirrhosis risk score (CRS) to predict liver fibrosis progression in HIV/hepatitis C virus (HCV)-coinfected patients.
  DESIGN: Retrospective follow-up study.
  METHODS: Based on a minimum follow-up time of 10 years with HCV infection, 190 HIV/HCV-coinfected patients were classified according to their METAVIR score: (1) 25 nonprogressor patients who did not develop fibrosis (F0) and (2) 165 progressor patients who developed fibrosis (F ≥ 1). Seven polymorphisms of CRS signature and IL28B genotype were performed using the GoldenGate assay. The CRS signature was calculated by naive Bayes formula as previously described.
  RESULTS: Nonprogressors had CRS values significantly lower than progressors (0.61 versus 0.67; P = 0.043). Among the progressors, we observed similar CRS values through all the fibrosis stages (F1/F2/F3/F4). The percentage of patients with CRS > 0.70 (high risk of developing fibrosis) was higher in progressors than in nonprogressors; but the percentages with values between 0.50 and 0.70 (intermediate risk) and <0.50 (low risk) were quite similar for each of the fibrosis stages (P = 0.047). The area under the receiver-operating characteristic curve of CRS for discriminating nonprogressor versus progressor was 0.625 (P = 0.043). When clinical variables were considered (age at HCV infection, intravenous drug use, gender, IL28B, and HCV genotype), the area under the receiver-operating characteristic curve of CRS improved up to 0.739 (P < 0.001).
  CONCLUSIONS: CRS itself seems not to be a good marker for identifying HIV/HCV-coinfected patients who are at high risk of developing liver fibrosis. However, CRS score coupled with clinical factors might help to distinguish between nonprogressors and progressors patients.
  

  PMID: 23797694 [PubMed - indexed for MEDLINE]

• European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy. -

  Related Articles

  European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy.

  J Antimicrob Chemother. 2013 Oct;68(10):2349-57

  Authors: Guzmán-Fulgencio M, Berenguer J, Micheloud D, Fernández-Rodríguez A, García-Álvarez M, Jiménez-Sousa MA, Bellón JM, Campos Y, Cosín J, Aldámiz-Echevarría T, Catalán P, López JC, Resino S

  Abstract
  BACKGROUND: There is substantial interindividual variability in the rate and extent of CD4+ T cell recovery after starting combination antiretroviral therapy (cART). The aim of our study was to determine whether mitochondrial DNA (mtDNA) haplogroups are associated with recovery of CD4+ in HIV-infected patients on cART.
  METHODS: We carried out a retrospective study on 275 cART-naive patients with CD4+ counts <350 cells/mm(3), who were followed-up during at least 24 months after initiating cART. mtDNA genotyping was performed by Sequenom's MassARRAY platform.
  RESULTS: Patients within cluster JT and haplogroup J had a lower chance of achieving a CD4+ count ≥500 cells/mm(3) than patients within cluster HV and haplogroup H [hazard ratio (HR) = 0.68 (P = 0.058) and HR = 0.48 (P = 0.010), respectively]. The time of follow-up during which the CD4+ count was ≥500 cells/mm(3) was longer in haplogroups HV and H than in haplogroups JT and J [20 months versus 6.2 months (P = 0.029) and 20 months versus 0 months (P = 0.024), respectively]. Additionally, haplogroups HV and H had greater chances of achieving a CD4+ count ≥500 cells/mm(3) during at least 12, 36, 48 and 60 months post-cART initiation compared with patients within haplogroups JT and J. Patients within haplogroup T only had a lesser chance of achieving a CD4+ count ≥500 cells/mm(3) during at least 48 months and 60 months post-cART initiation.
  CONCLUSION: European mitochondrial haplogroups might influence CD4+ recovery in HIV-infected patients following initiation with cART. Haplogroups J and T appear to be associated with a worse profile of CD4+ recovery, whereas haplogroup H was associated with a better CD4+ reconstitution.
  

  PMID: 23749950 [PubMed - indexed for MEDLINE]

• Mitochondrial haplogroups are associated with clinical pattern of AIDS progression in HIV-infected patients. -

  Related Articles

  Mitochondrial haplogroups are associated with clinical pattern of AIDS progression in HIV-infected patients.

  J Acquir Immune Defic Syndr. 2013 Jun 1;63(2):178-83

  Authors: Guzmán-Fulgencio M, Jiménez JL, García-Álvarez M, Bellón JM, Fernández-Rodriguez A, Campos Y, Rodríguez C, González-Garcia J, Riera M, Viciana P, Muñoz-Fernández MÁ, Resino S

  Abstract
  We performed a cross-sectional study in 469 HIV-infected patients, whose mitochondrial haplogroups were genotyped to study their association with the clinical pattern of AIDS progression. The chance of not having an AIDS progression was 1.45 [95% of confidence interval (CI) = 1.02 to 2.05, P = 0.035) times greater in patients with cluster HV and 1.51 (95% CI = 1.06 to 2.18, P = 0.021) times greater in patients with haplogroup H. However, we only found significant values for haplogroup H (odds ratio = 1.52, 95% CI = 1.01 to 2.32, P = 0.049) in an ordinal logistic regression adjusted by gender, age at HIV infection, intravenous drug users, and hepatitis C virus infection. These data suggest that mitochondrial haplogroups might play a significant role in AIDS progression.
  

  PMID: 23666137 [PubMed - indexed for MEDLINE]

• IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients. -

  Related Articles

  IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients.

  J Viral Hepat. 2013 May;20(5):358-66

  Authors: Jiménez-Sousa MA, Berenguer J, Rallón N, Guzmán-Fulgencio M, López JC, Soriano V, Fernández-Rodríguez A, Cosín J, Restrepo C, García-Álvarez M, Miralles P, Benito JM, Resino S

  Abstract
  Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.
  

  PMID: 23565619 [PubMed - indexed for MEDLINE]