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High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability, or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with prefrailty. Thus, our objective was to study the association of hsCRP and Hcy with prefrailty and frailty in 1,211 Spanish men and women aged 65â 98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Friedâ s criteria. Hcy was independently associated with frailty (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.01â 1.12), whereas hsCRP was independently associated with both prefrailty (OR = 1.03; 95% CI: 1.01â 1.06) and frailty (OR = 1.07; 95% CI: 1.02â 1.12). Furthermore, both markers were positively correlated with the number of Friedâ s criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR = 1.03, 95% CI: 1.00â 1.06), weakness (hsCRP: OR = 1.03, 95% CI: 1.01â 1.05), and low physical activity (hsCRP: OR = 1.04, 95% CI: 1.02â 1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength, and decreased physical activity., This study was supported by the Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad; RD06/0013/0001, and RD12/0043/0012). Ministerio de Ciencia e Innovación; PI07/90175). NA-S was supported by fellowships from the Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad; RD06/0013/0001 and RD12/0043/0012) and by a fellowship from the Consejería de Salud, Junta de Andalucía (PC-0111-2016-0111). IC-C was supported by fellowships from the Ministerio de Educación, Cultura y Deporte (FPU13/01210) and Junta de Andalucía (CTS160).

15 Páginas.-- 6 Figuras.-- 1 Tabla, Metabolic-associated fatty liver disease (MAFLD) is the most important cause of liver disease worldwide. It is characterized by the accumulation of fat in the liver and is closely associated with abdominal obesity. In addition, oxidative stress and inflammation are significant features involved in MAFLD. Recently, our group demonstrated that lupin protein hydrolysates (LPHs) had lipid lowering, antioxidant, and anti-inflammatory effects. Sixty male mice fed with a Western diet were intragastrically treated with LPHs (or vehicle) for 12 weeks. Liver and adipose tissue lipid accumulation and hepatic inflammatory and oxidant status were evaluated. A significant decrease in steatosis was observed in LPHs-treated mice, which presented a decreased gene expression of CD36 and LDL-R, crucial markers in MAFLD. In addition, LPHs increased the hepatic total antioxidant capacity and reduced the hepatic inflammatory status. Moreover, LPHs-treated mice showed a significant reduction in abdominal adiposity. This is the first study to show that the supplementation with LPHs markedly ameliorates the generation of the steatotic liver caused by the intake of a Western diet and reduces abdominal obesity in ApoE−/− mice. Future clinical trials should shed light on the effects of LPHs on MAFLD., This research was funded by the Spanish Government, Ministerio de Economía y Competitividad [AGL2012-40247-C02-01 and AGL2012-40247-C02-02], the Andalusian Government Ministry of Health [PC-0111-2016-0111], and the PAIDI Program from the Andalusian Government [CTS160]. G.S.-S. and I.C.-C. were supported by FPU grants from the Spanish Ministerio de Educación, Cultura y Deporte, [FPU16/02339] and [FPU13/01210], respectively. N.Á.-S. was supported by a fellowship from the National Net RETICEF for Aging Studies (RD12/0043/0012 from the Instituto de Salud Carlos III, Spanish Ministerio de Ciencia e Innovación). B.R.-O. was supported by a grant from European Social Fund and Spanish Ministerio de Empleo y Seguridad Social [EJ-086]. A.I.Á.-L. was funded by the Andalusian Government Ministry of Health [PI-0136-2019]. I.B. was supported by the VI Program of Inner Initiative for Research and Transfer of University of Seville (VI PPIT-US).

10 Páginas.-- 4 Figuras.-- 8 Tablas, Scope We have previously demonstrated the anti-inflammatory and antioxidant properties of in vitro administered Lupinus angustifolius protein hydrolysates (LPHs) on human peripheral blood mononuclear cells (PBMCs). This study aims to evaluate the safety and efficacy of a beverage containing LPHs (LPHb) on the immune, oxidative and metabolic status of healthy subjects. Methods and Results In this open-label intervention, 33 participants daily ingest a LPHb containing 1 g LPHs for 28 days. Biochemical parameters are assayed in fasting peripheral blood and urine samples before, during (14 days) and after LPHb ingestion. Participants’ health status and the immune and antioxidant responses of PBMCs are also evaluated throughout the trial. The LPHb ingestion is safe and effective in both increasing the anti-/pro-inflammatory response of PBMCs and improving the cellular anti-oxidant capacity. LPHb also reduces the low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C) atherogenic index. LPHb effect is particularly beneficial on decreasing not only the LDL-C/HDL-C index but also serum total cholesterol levels in the male cohort that shows the highest baseline levels of well-known cardiovascular risk factors. Conclusion This is the first study to show the pleiotropic actions of a lupine bioactive peptides-based functional food on key steps of atherosclerosis including inflammation, oxidative stress, and cholesterol metabolism., Ministerio de Economía y Competitividad. Grant Numbers: AGL2012-40247-C02-01, AGL2012-40247-C02-02 Programa PAIDI Junta de Andalucia. Grant Number: CTS160 Ministerio de Educación, Cultura y Deporte. Grant Numbers: FPU13/01210, FPU16/02339 Ministerio de Ciencia e Innovación (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad; RETICEF). Grant Numbers: RD06/0013/0001, RD12/0043/0012 Universidad de Sevilla. Grant Numbers: V PPIT-US, VI PPIT-US Consejería de Salud y Familias, Junta de Andalucía. Grant Number: PC-0111-2016-0111

Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

Between 15% and 30% of HIV‐infected subjects fail to increase their CD4+ T‐cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad‐MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad‐MSC infusions. They had a median CD4+ nadir count of 16/μL (range, 2‐180) and CD4+ count of 253 cells per microliter (171‐412) at baseline after 109 (54‐237) months on antiretroviral treatment and 69 (52‐91) months of continuous undetectable plasma HIV‐RNA. After a year of follow‐up, an independent committee recommended the suspension of the study because no increase of CD4+ T‐cell counts or CD4+/CD8+ ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV‐DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad‐MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad‐MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004. EudraCT number: 2014‐000307‐26., Between 15%‐30% of HIV‐infected subjects, do not achieve a significant immune recovery despite continuous viral suppression (immunological non‐responders). These subjects have an aberrant state of immune activation and inflammation. The treatment with adipose tissue allogeneic adult mesenchymal stromal cells does not neither improve immune recovery, nor has it succeeded in reducing the state of immune activation and inflammation.

The activation phenotypes and functional changes in monocyte subsets during hepatitis C virus (HCV) elimination in HIV/HCV-coinfected patients were evaluated. Twenty-two HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antiviral (DAA) therapy and 10 HIV-monoinfected patients were included. The activation phenotype (10 markers) and polyfunctionality (intracellular interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-10 production) in three monocyte subsets (classical, intermediate, and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV DNA levels were assayed by droplet digital PCR. After HCV clearance, there was a significant increase in classical monocyte and decreases in intermediate and nonclassical monocyte levels. The levels of the activation markers CD49d, CD40, and CX3CR1 were decreased after treatment in the monocyte subsets, reaching the levels in HIV-monoinfected patients. After lipopolysaccharide (LPS) stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations, such as the IL-1α− (IL-1α-negative) IL-1β− IL-6+ (IL-6-producing) IL-8− TNF-α− IL-10− combination, were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV DNA levels correlated with activation markers before but not after treatment. HCV clearance after DAA treatment in patients on cART exerts an anti-inflammatory profile on monocyte subsets, activation phenotypes, and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients., This work was supported by the Instituto de Salud Carlos III (research contracts CPII014/00025 to E.R.-M., CP19/00159 to A.G.-V., FI17/00186 to M.R.J.-L., and FI14/00431 to L.T.-D. and research projects PI16/00684 and PI19/01127 to E.R.-M.) and the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020 and RD16/0025/0019), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016, Instituto de Salud Carlos III, Fondos FEDER. E.R.-M. was supported by the Consejería de Salud y Bienestar Social of the Junta de Andalucía through the Nicolás Monardes program (C-0032/17).

Background Optimal haemostasis management in orthotropic liver transplant (OLT) could reduce blood loss and transfusion volume, improve patient outcomes and reduce cost. Methods We performed a study including 336 OLTs to evaluate the clinical and cost effectiveness of a new point-of-care (POC)-based haemostatic management approach in OLT patients. Results In terms of health benefit we found that the new approach showed a significant reduction in transfusion requirements (red blood cell transfusion units were reduced from 5.3±4.6 to 2.8±2.9 [p Conclusions POC haemostatic monitoring during OLT is cost effective.

Background Homocysteine (Hcy) high levels are associated with fractures, bone resorption and an early onset of osteoporosis in elderly persons; a relationship between Hcy and bone formation has also been suggested but is still controversial. Frailty, an independent predictor of fractures and decreased bone mineral density is associated with altered bone metabolism in women. However, no previous works have studied the relationship among frailty, Hcy levels and bone turnover. Methods We studied the association among Hcy, osteoporosis and N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (β-CTX), parathyroid hormone (PTH), calcium and 25-hydroxyvitamin D (25(OH)D) in 631 Spanish women between the ages of 65–78 from the Toledo Study for Healthy Aging (TSHA) cohort, who were classified as highly functional (robust subjects) or non-robust (pre-frail or frail subjects) according to Fried's criteria. Results Hcy was independently associated with β-CTX in the entire population (B = 0.22; 95% CI, 0.09–0.34; p = 0.001) and in the non-robust group (B = 0.24; 95% CI, 0.09–0.39; p = 0.002). Hcy was also associated with PINP in the entire and non-robust populations, but the association was lost after including the levels of β-CTX, but not the other bone biomarkers, in the multivariate analysis. This suggests that the controversial relationship between Hcy and bone formation might be explained, at least to a certain extent, by the confounding effects of β-CTX. Conclusions This work highlights the important implication of frailty status in the association between Hcy and increased bone turnover in older women.

[Background] Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness., [Methods] Subjects (> 60 years old) who were vaccinated against influenza virus were included, and the vaccine response was measured by a haemagglutination inhibition (HAI) test. At baseline, peripheral CD4 and CD8 T-cells were phenotypically characterized. Thymic function and the levels of different inflammation-related biomarkers, including Lipopolysaccharide Binding Protein (LBP) and anti-cytomegalovirus (CMV) IgG antibodies, were also measured., [Results] Influenza vaccine non-responders showed a tendency of higher frequency of regulatory T-cells (Tregs) before vaccination than responders (1.49 [1.08–1.85] vs. 1.12 [0.94–1.63], respectively, p = 0.061), as well as higher expression of the proliferation marker Ki67 in Tregs and different CD4 and CD8 T-cell maturational subsets. The levels of inflammation-related biomarkers correlated with the frequencies of different proliferating T-cell subsets and with thymic function (e.g., thymic function with D-dimers, r = − 0.442, p = 0.001)., [Conclusions] Age-related homeostatic dysregulation involving the proliferation of CD4 and CD8 T-cell subsets, including Tregs, was related to a limited responsiveness to influenza vaccination and a higher inflammatory status in a cohort of elderly people., This work was supported by grants from the Fondo de Investigación Sanitaria (FIS; PI18/01216), which is co-funded by Fondos Europeos para el Desarrollo Regional (FEDER) and the Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo (Proyecto de Investigación de Excelencia; CTS2593). The Spanish AIDS Research Network of Excellence also supported this study (RD16/0025/0019). YM.P was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the “Nicolás Monardes” programme (C-0013-2017).

[Objective] Cardiovascular diseases (CVDs) are one of the main causes of morbimortality in HIV-infected patients on suppressive antiretroviral therapy. The objective of this work was to evaluate the role of single nucleotide polymorphisms (SNPs) in lipopolysaccharide (LPS) Toll-like receptor 4 (TLR4) and CVDs occurrence in HIV-infected patients. Additionally, the functional consequences of carrying these SNPs were analyzed., [Methods] The association of TLR4 SNPs, Asp299Gly/Thr399Ile with CVDs occurrence was analyzed using multivariate logistic regression models. Clinical, immunological, and traditional cardiovascular risk factors were used as covariates. The monocyte phenotype and response were assessed by multiparametric flow cytometry comparing carriers with noncarriers of this SNP., [Results] Asp299Gly SNP, assayed in 253 HIV-infected patients, was independently associated with the occurrence of CVDs after adjusting for CD4+ T-cell nadir, HCV-coinfection, bacterial pneumonia, diabetes mellitus, and traditional cardiovascular risk factors [odds ratio (confidence interval 95%) = 3.672 (1.061–12.712), P = 0.04). Carriers of Asp299Gly SNP showed higher percentage of patrolling and intermediate monocytes producing a proinflammatory combination of cytokines compared with noncarriers (P = 0.037 and P = 0.046, respectively). Intermediate monocyte subset levels correlated with soluble interleukin-6 levels only in carriers (r = 0.89; P = 0.01)., [Conclusion] TLR4 Asp299Gly polymorphism is independently associated with the occurrence of CVDs in HIV-infected patients. The proinflammatory profile associated to this variant could be involved in the development of atherosclerotic pathologies.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antinuclear autoantibodies. In addition, the involvement of CD4+ T-helper (Th) cells in SLE has become increasingly evident. Although the role of melatonin has been tested in some experimental models of lupus with inconclusive results, there are no studies evaluating the melatonin effect on cells from patients with SLE. Therefore, the aim of this study was to analyse the role of in vitro administered melatonin in the immune response of peripheral leukocytes from treated patients with SLE (n = 20) and age- and sex-matched healthy controls. Melatonin was tested for its effect on the production of key Th1, Th2, Th9, Th17 and innate cytokines. The frequency of T regulatory (Treg) cells and the expression of FOXP3 and BAFF were also explored. Our results are the first to show that melatonin decreased the production of IL-5 and to describe the novel role of melatonin in IL-9 production by human circulating cells. Additionally, we highlighted a two-faceted melatonin effect. Although it acted as a prototypical anti-inflammatory compound, reducing exacerbated Th1 and innate responses in PHA-stimulated cells from healthy subjects, it caused the opposite actions in immune-depressed cells from patients with SLE. Melatonin also increased the number of Treg cells expressing FOXP3 and offset BAFF overexpression in SLE patient cells. These findings open a new field of research in lupus that could lead to the use of melatonin as treatment or cotreatment for SLE.

Immunological characterization of HIV-infected subjects with low CD4-recovery (LR-subjects) has been extensively performed after a variable period of combined antiretroviral therapy (cART). We now explore immunological alterations present before the cART onset. In a case-control study, we selected pre-cART samples of HIV-subjects with and without low CD4-recovery after CART (n = 21 per group). CD4 T-cell activation, senescence and exhaustion related markers were not found specifically altered before cART initiation. On the other hand, we found that LR-subjects before cART already showed increased levels of IL6 (p = 0.009) and increased frequencies of Ki67+FCD4(+) T-cells (p = 0.026), CD45RA-CD27+CD4(+) T-cells (p = 0.008) and Treg (p = 0.001), as well as increased expression of CD95 and CD127 on CD4 T-cells (p = 0.016; p = 0.032, respectively). These parameters characterize the immunological damage in LR-subjects before the cART onset and could be associated to the mechanisms hindering the subsequent CD4 recovery. (C) 2017 Elsevier B.V. All rights reserved.

Frail older people are at high risk for fractures and falls increasing the rates of institutionalization and mortality. Bone markers have been related to both aging and fractures. However, no previous reports have shown a potential relationship between serum bone markers such as N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (β-CTX) and parathyroid hormone (PTH) with frailty in elderly female populations. This study is aimed at examining the associations of bone metabolism markers and frailty in older Spanish women through a descriptive cross-sectional analysis based on a cohort of the Toledo Study for Healthy Aging (TSHA). The levels of serum PINP, β-CTX, PTH and 25-hydroxyvitamin D (25(OH)D) were assessed in 592 participants (median age 74years) who were defined as robust, prefrail and frail according to Fried's approach. Frail subjects had significantly high levels of PINP, β-CTX and PTH and low production of 25(OH)D. After adjustment for confounders, high PINP levels (defined by the upper quartile) and low levels of 25(OH)D (lower quartile) remained significantly associated to frailty [OR for PINP: 2.19 (95% CI, 1.15-4.18; P=0.017); OR for 25(OH)D: 1.65 (95% CI, 1.02-2.67; P=0.042)]. Women with both high PINP levels and low 25(OH)D levels presented a 5.85-fold increased frailty risk (95% CI, 1.64-20.93; P=0.007). The main contribution of this paper is the novel definition of PINP and 25(OH)D markers as potential biomarkers of frailty and targets for intervention.

Optimal haemostasis management can improve patient outcomes and reduce blood loss and transfusion volume in orthotopic-liver-transplant (OLT).We performed a prospective study including 200 consecutive OLTs. The first 100 patients were treated according to the clinic's standards and the next 100 patients were treated using the new point-of-care (POC)-based haemostasis management strategy. Transfusion parameters and other outcomes were compared between groups.Transfusion requirements were reduced in the POC group. The median and IQR of red-blood-cells (RBC) transfusion units were reduced from 5 [2-8] to 3 [0-5] (p0.001), plasma from 2 [0-4] to 0 (p0.001), and platelets from 1 [0-4] to 0 [0-1] (p0.001), into the POC group only four patients received tranexamic acid and fibrinogen transfusion rate was 1.13 ± 1.44 g (p = 0.001). We also improved the incidence of transfusion avoidance, 5% vs. 24% (p0.001) and reduced the incidence of massive transfusion (defined as the transfusion of more than 10 RBC units), 13% vs. 2% (p = 0.005). We also observed a relationship between RBC transfusion requirements and preoperative haemoglobin, and between platelet transfusion and preoperative fibrinogen levels. The incidence of postoperative complications, such as, reoperation for bleeding, acute-kidney-failure or haemodynamic instability was significantly lower (13.0% vs. 5%, p = 0.048, 17% vs. 2%, p0.001, and 29% vs. 16%, p = 0.028). Overall, blood product transfusion was associated with increased risk of postoperative complications.A haemostatic therapy algorithm based on POC monitoring reduced transfusion and improved outcome in OLT.

BACKGROUND Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known. METHODS We analysed soluble inflammatory levels [high-sensitivity C-reactive protein, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and IL-17] in a cohort of viraemic HIV-infected patients compared with (i) age-matched, (ii) elderly and (iii) non-survivor elderly, uninfected healthy controls. We longitudinally analysed the effect of long-term 48 and 96 week suppressive combined antiretroviral therapy (cART) on the soluble inflammatory levels compared with those found in control subjects. RESULTS Baseline IL-6 and IL-8 levels were at similar or lower concentrations in untreated patients compared with healthy elderly individuals. However, TNF-α and IFN-γ levels broadly exceeded those found in survivors and non-survivor elderly individuals. Long-term suppressive cART normalized most of the inflammatory markers, with the exception of TNF-α levels, which persisted as high as those in elderly non-survivor controls. CONCLUSIONS Chronic inflammatory alterations associated with HIV infection are maintained at a different level from those of ageing. The persistent alteration of TNF-α levels in HIV-infected patients might cause tissue damage and have implications for developing non-AIDS-defining illnesses, even when HIV replication is long-term controlled by cART.

The potential effect of blocking the CCR5 receptor on HIV disease progression biomarkers is not well understood. We showed that an 8-day maraviroc (MVC) monotherapy clinical test (MCT) can be used in selecting patients to receive MVC-containing combined antiretroviral therapy (cART). Using this MCT model, we assessed the effect of MVC on several HIV disease progression biomarkers during the MCT (MVC-specific effect) and following short-term (12-week) cART. We compared 45 patients on MVC monotherapy with a control group of 25 patients on MVC-sparing cART. We found that MVC did not modify any biomarkers in patients that had no virological response after the MCT. MVC-specific effects in patients with virological responses included increased CD8 + T-cell activation and senescence levels, preservation of an increase in soluble CD14 (sCD14), and a decrease in D dimer levels. After 12 weeks, MVC-containing cART increased CD8 + T-cell counts and preserved CD4 + T-cell senescence levels compared with MVC-sparing cART. Moreover, there was a decrease in sCD14 levels in patients that received MVC-containing cART. In conclusion, effects compatible with CD8 + T-cell redistribution in peripheral blood were observed after MVC therapy. However, MVC was associated with a favorable profile in HIV disease progression biomarkers only in patients with a virological response. These results support a potential clinical benefit of a therapy which includes MVC in HIV-infected patients. Copyright © 2012, American Society for Microbiology. All Rights Reserved., This work was supported by Pfizer/ViiV Healthcare (grant number WS843473) and by Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD06/0006/0021), Fondo de Investigación Sanitaria (grant PS09/01595), and the Fondos Europeos para el Desarrollo Regional (FEDER). S.F.M. and E.R.M. have grants from the Fondo de Investigaciones Sanitarias (CD10/00382 and CP08/00172, respectively). Manuel Leal has a grant from Pfizer.

Objectives: Bacterial lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels have been indistinctly used to measure bacterial translocation independently of the immunovirological stage in HIV infection; however, when the association of both markers with different HIV-progression end-points has been studied, discrepant results have been reported. The aim of this study was to assess the relationship between LPS and sCD14 in different HIV-infection immune stages and to determine the relationship between these biomarkers with established HIV-disease-progression-related markers, as T-cell immune activation, high-sensitivity C-reactive protein and D-dimer. Methods: Seventy-three chronically HIV-1-infected patients with detectable HIV-1 RNA levels were analyzed. LPS levels by use of limulus lysate assay, sCD14, intestinal fatty acid binding protein and inflammation-coagulation-associated biomarkers were assessed. Results: In this study, we found that LPS and sCD14 levels were only associated when low CD4+ T-cell levels and high HIV RNA levels were present. In addition, only sCD14 levels, but not LPS, were independently associated with HIV-disease progression-related markers, supporting the clinical importance of sCD14. Conclusions: These results indicate that LPS and sCD14 have a different biological significance and should not be indistinctly used without taking the HIV immunovirological stage into account. © 2012 The British Infection Association., This study was supported by Pfizer (Project Number WS843473) and Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD06/0006/0021, RD06/0006/0035 and RD06/0006/1004), Fondo de Investigación Sanitaria grants PI07/0976 and by the Fondos Europeos para el Desarrollo Regional (FEDER). YMP, SFM and ERM have grants from the Fondo de Investigaciones Sanitarias (CP07/00172, CD10/00382 and CP08/00172, respectively).