Epidemiology of fungal infection in COVID 19 in Spain during 2020 and 2021: a nationwide study.

We realize a nationwide population-based retrospective study to analyze the characteristics and risk factors of fungal co-infections in COVID-19 hospitalized patients as well as describe their causative agents in the Spanish population in 2020 and 2021. Data were obtained from records in the Minimum Basic Data Set of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health, and annually published with two years lag. The assessment of the risk associated with the development of healthcare-associated fungal co-infections was assessed using an adjusted logistic regression model. The incidence of fungal co-infection in COVID-19 hospitalized patients was 1.41%. The main risk factors associated were surgery, sepsis, age, male gender, obesity, and COPD. Co-infection was associated with worse outcomes including higher in-hospital and in ICU mortality, and higher length of stay. Candida spp. and Aspergillus spp. were the microorganisms more frequent. This is the first study analyzing fungal coinfection at a national level in hospitalized patients with COVID-19 in Spanish population and one of the few studies available that demonstrate that surgery was an independent risk factor of Aspergillosis coinfection in COVID-19 patients.

Epidemiology of bacterial co-infections and risk factors in COVID-19-hospitalized patients in Spain: a nationwide study.

BACKGROUND: We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome. METHODS: Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model. RESULTS: The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second. CONCLUSIONS: Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.

COVID-19 in donation and transplant.

SARS-CoV-2 infection has had a major impact on donation and transplantation. Since the cessation of activity two years ago, the international medical community has rapidly generated evidence capable of sustaining and increasing this neccesary activity. This paper analyses the epidemiology and burden of COVID-19 in donation and transplantation, the pathogenesis of the infection and its relationship with graft-mediated transmission, the impact of vaccination on donation and transplantation, the evolution of donation in Spain throughout the pandemic, some lessons learned in SARS-CoV-2 infected donor recipients with positive PCR and the applicability of the main therapeutic tools recently approved for treatment among transplant recipients.

Bacterial translocation and clinical progression of HCV-related cirrhosis in HIV-infected patients.

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV-coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well-conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver-related death (LRD) and death of any cause. After a median (Q1-Q3) follow-up of 51 (27-72) months, 67 patients (24%; 95% CI: 19-29) developed their first LD or died during follow-up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83-196, 197-355, >355 [copies/µL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1-0.6, 0.6-1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis.

Trends in nontuberculous mycobacterial disease in hospitalized subjects in Spain (1997-2010) according to HIV infection.

OBJECTIVES: The aim of the study was to estimate the incidence of nontuberculous mycobacterial (NTM) disease and the rate of NTM disease-related mortality and to analyse trends in these variables according to HIV infection. METHODS: We performed a retrospective study for the period 1997-2010 using data from the Minimum Basic Data Set (MBDS) provided by the Spanish Ministry of Health. The exposure variables were: (i) HIV infection (HIV positive versus HIV negative); (ii) calendar period in relation to widespread use of combination antiretroviral therapy (cART) [1997-1999 (early cART period), 2000-2003 (middle cART period) and 2004-2010 (late cART period)]. The outcome variables were (i) new NTM disease diagnosis and (ii) mortality. RESULTS: A total of 3729 cases of incident NTM disease were collected in MBDS, 1795 in the HIV-negative group and 1934 in the HIV-positive group, among whom 602 deaths occurred, 223 in the HIV-negative group and 379 in the HIV-positive group. The incidence of NTM disease and the rate of NTM disease-related mortality were 1000-fold higher in the HIV-positive group than in the HIV-negative group. Regarding the incidence of NTM disease, in the HIV-negative group the incidence increased from 2.91 to 3.97 events per 1,000,000 patient-years from 1997-1999 to 2004-2010 (P < 0.001), while in the HIV-positive group the incidence decreased from 2.29 to 0.71 events per 1000 patient-years from 1997-1999 to 2004-2010 (P < 0.001). Regarding mortality, in the HIV-negative group mortality increased from 2.63 to 4.26 events per 10,000,000 patient-years from 1997-1999 to 2000-2003 (P = 0.059), and then the rate stabilized at around 3.87 events per 10,000,000 patient-years in 2004-2010 (P = 0.128), while in the HIV-positive group mortality decreased from 4.28 to 1.39 events per 10,000 patient-years from 1997-1999 to 2004-2010 (P < 0.001). CONCLUSIONS: HIV infection was associated with a higher NTM disease incidence and higher NTM disease-related mortality than in the general population, but these rates decreased in the HIV-positive group from 1997-1999 to 2004-2010, whereas the NTM disease incidence increased in the HIV-negative group.

Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

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

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.

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

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.

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

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.

Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus.

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.

Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients.

The efficacy of current hepatitis C therapy in HIV/HCV-coinfected patients is largely dependent on HCV genotype. The annual prevalence of HCV genotypes/subtypes and their influence on HCV clearance with antiviral treatment were examined in a dynamic cohort of HIV/HCV-coinfected patients followed up in Madrid since 2000. Patients entered the cohort at first visit and left the cohort when HCV clearance was achieved with HCV therapy or when follow-up was interrupted for any reason, including death. A total of 672 HIV/HCV-coinfected patients constituted the cohort. The mean follow-up time was 5.5 years, corresponding to 4108 patient-years. Mean age at entry was 37 years, and 73% were men and 86% were intravenous drug users. Overall distribution of HCV genotypes was as follows: 57.1% HCV-1 (1a: 29.2%, 1b: 20.4%, unknown: 7.6%), 1.3% HCV-2, 25.4% HCV-3 and 15.9% HCV-4. A total of 274 (40.8%) patients were treated with peginterferon-ribavirin, of whom 116 (42.3%) achieved HCV clearance following 1-3 courses of therapy. The proportion of HCV-1/4 rose from 71.7% in 2000 to 76.8% in 2008, whereas the proportion of HCV-2/3 fell from 28.1% in 2000 to 23.2% in 2008. The yearly prevalence increased for HCV-1 (R(2) : 0.92, b: 0.59, P < 0.001) and HCV-4 (R(2) : 0.77, b: 0.33, P < 0.005) and conversely diminished for HCV-3 (R(2) : 0.94, b: -0.82, P < 0.001). In summary, the prevalence of HCV-1 and HCV-4 has increased over the last decade in HIV/HCV-coinfected patients, whereas conversely it has declined for HCV-3, in association with the wider use of HCV therapy (41%) in this population.

Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naive vertically HIV-infected children on highly active antiretroviral therapy(HAART). PATIENTS AND METHODS: We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. RESULTS: We found hypercholesterolaemia (4200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (4170 mg/dL) in 14.3, 8.3, 13,4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (Po0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART.At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy,and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores 2. CONCLUSIONS: HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.

Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006).

OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. METHODS: An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1. CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients.

BACKGROUND: CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. METHODS: We carried out a cross-sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-alpha and ribavirin. T- and B-cell subsets were analysed by flow cytometry. RESULTS: We found that HIV/HCV coinfected patients with HCV-RNA > or =850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L- and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81-CD62L+ and higher values of CD3+CD81+CD62L- and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L- subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. CONCLUSIONS: We observed a different pattern of CD81 T-cell and B-cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

High rate of infection and immune disorders in patients with hepatitis C virus after liver transplantation.

The aim of this prospective study was to analyze the incidence of serious infections and changes in immunological markers after liver transplantation (LT) in a cohort of patients with hepatitis C virus (HCV). This study included 34 patients who had LT, 20 patients with HCV etiology (HCV group), and 14 patients with alcoholic etiology (non-HCV group). Patients with HCV were more likely to have severe infections (80%) in comparison with patients in the non-HCV group (42%) (P=0.05). The HCV group had a 3-fold greater likelihood of early severe bacterial infections than the non-HCV group. At 1 week post LT, the HCV group showed higher values of CD19+ B cells/microL than the non-HCV group (P<0.05). At weeks 4 and 12 post LT, the HCV group had lower values of CD19+ B cells/microL (P<0.05). Our data suggest that HCV recurrence after LT was associated with a high incidence of early severe infections and immunological alterations, which may be related to this increased risk.

Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence.

This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage > or =F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient > or=6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients (P<0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49-0.91; P=0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54-0.94; P=0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67-0.98; P=0.005), and HA (AUC: 0.80; CI 95%: 0.55-0.94; P=0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.

Identification of liver fibrosis in HIV/HCV-coinfected patients using a simple predictive model based on routine laboratory data.

We constructed noninvasive models to predict significant fibrosis (F > or = 2) and advanced fibrosis (F > or = 3) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients, naïve for anti-HCV treatment. A total of 296 patients with liver biopsy were randomly assigned to an estimation group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the Hospital Gregorio Marañón (HGM)-1 index, based on platelet count, aspartate aminotransferase (AST) and glucose, to predict F > or = 2 and the HGM-2 index, based on platelet count, international normalized ratio, alkaline phosphatase and AST to predict F > or = 3. The area under the receiver operating characteristic curves (AUROCs) of the HGM-1 index for the EG and the VG were 0.807 and 0.712 respectively. The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and 0.815 respectively. With the HGM-1 index applied to the VG, using best cutoff scores, the negative predictive value (NPV) to exclude F > or = 2 was 54.5% and the positive predictive value (PPV) to confirm F > or = 2 was 93.3%. With the HGM-2 index applied to the VG, using best cutoff scores, the NPV to exclude F > or = 3 was 92.3, and the PPV to confirm F > or = 3 was 64.3%. Thus, HGM-2 accurately predicted F > or = 3 among HIV/HCV-coinfected patients. HGM-1 was less accurate at predicting F > or = 2.

La terapia combinada puede ser tan efectiva como la terapia antirretroviral de alta eficacia en el control de la carga viral en niños con un sistema inmunitario conservado / Combination therapy can be as effective as highly active antiretroviral therapy in controlling viral load in children with a preserved immune system

Objetivo: Comparar la efectividad de la terapia combinada (TC) y del tratamiento antirretroviral de alta eficacia (TARGA) en el control de la replicación viral en una cohorte de niños infectados por el virus de la inmunodeficiencia humana tipo 1 (VIH-1) con un sistema inmunitario relativamente conservado. Material y métodos: Realizamos un estudio observacional en 21 niños infectados verticalmente por el VIH-1 con terapia antirretroviral(TAR), comparando la efectividad de la TC y del TARGA, en el control de la carga viral (CV) plasmática. Principales variables evaluadas: Las principales variables medidas fueron la presencia de carga viral indetectable (400 copias/ml) y el desarrollo de fracasos virológicos tras alcanzaruna CV indetectable con rebotes de CV (>400 y/o >5.000 copias/ml). Resultados: Los niños con TARGA alcanzaban CV indetectables más precozmente. La media de tiempo para alcanzar CV indetectable fue de 8,1 +/- 3,7 meses en el grupo de TC y de 2,9 +/- 0,2 meses en el grupo con TARGA (p 400 copias/mL. El tiempo mediopara el aumento de CV >400 y CV >5.000 copias/mL fue similaren ambos grupos (p >0,05). Ocho niños del grupo de la TC y6 del grupo con TARGA presentaron un rebote de CV >5.000 copias/mL. En ninguno de los dos grupos hubo reducción en el porcentaje de CD4+, que se mantuvo elevado durante todo el seguimiento. El porcentaje de niños con CV <5.000 copias/mL fue similar en ambos grupos. Conclusiones: Nuestro estudio muestra que la TC puedes ertan efectiva como el TARGA en niños infectados por el VIH con un sistema inmunitario relativamente conservado

Objective: To compare the effectiveness of combination therapy (CTI and highly active antiretroviral therapy (HAART} in the control of viral replication in a group of HIV-1-infected children with a relatively preserved immune system. Design and setting: For this purpose, we carried out an observational study in 21 vertically HIV-1-infected children on ART, comparing the effectiveness of CT and HAART regimens in the control of plasma viral load (VL). Main outcome measures: The outcome variables were undetectable VL (uVL; VL 400 copies/mL; VL >5.000 copies/mL). Results: The children on HAART achieved u VL at earlier timepoints. The median time required to achieve uVL was 8.1 +/- 3.7 months in the CT group and 2.9 +/- 0.2 months in the HAART group (p 400 copies/mL. The median time to a rebound of VL >400 and VL>5.000 copies/mL were similar in the two groups of children(p >0.05). Eight children in the CT group and 6 children in the HAART group presented a rebound of VL over 5.000 copies/mL. In the CT group and HAART group, there was no reduction of the mean %CD4+, which remained high throughout the follow uperiod. The percentage of HIV children with VL <5.000copies/mL was similar in the two groups. Conclusions: The present study suggests that CT may be justs a effective as HAART in children with a relatively preservedimmune system