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The single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene has been associated with the spontaneous clearance of hepatitis C virus. We sought to determine whether this SNP could be associated with the spontaneous control of human immunodeficiency virus (HIV) infection. We studied the prevalence of the IL28B CC genotype among 53 white HIV controllers, compared with the prevalence among 389 HIV-infected noncontrollers. We found that the IL28B CC genotype was independently associated with spontaneous HIV control (odds ratio [OR], 2.669; P = .017), as were female sex (OR, 7.077; P ≤ .001) and the presence of HLA-B57 and/or B27 (OR, 3.080; P = .017). This result supports the idea that common host mechanisms are involved in the spontaneous control of these 2 chronic infections. [ABSTRACT FROM AUTHOR]

Biobanks are infrastructures essential for research involving multi-disciplinary teams and an increasing number of stakeholders. In the field of personalized medicine, biobanks play a key role through the provision of well-characterized and annotated samples protecting at the same time the right of donors. The Andalusian Public Health System Biobank (SSPA Biobank) has implemented a global information management system made up of different modules that allow for the recording, traceability and monitoring of all the information associated with the biobank operations. The data model, designed in a standardized and normalized way according to international initiatives on data harmonization, integrates the information necessary to guarantee the quality of results from research, benefiting researchers, clinicians and donors.

Aging may enhance both oxidative stress and bone-marrow mesenchymal stem-cell (MSC) differentiation into adipocytes. That reduces osteoblastogenesis, thus favoring bone-mass loss and fracture, representing an important worldwide health-issue, mainly in countries with aging populations. Intake of antioxidant products may help to retain bone-mass density. Interestingly, a novel olive-pomace physical treatment to generate olive oil also yields by-products rich in functional antioxidants. Thus, diet of postmenopausal women was supplemented for two months with one of such by-products (distillate 6; D6), being rich in squalene. After treatment, serum from such women showed reduced both lipidic peroxidation and oxidized low-density lipoprotein (LDL). Besides, vitamin E and coenzyme Q10 levels increased. Furthermore, culture medium containing 10% of such serum both increased osteoblastogenesis and reduced adipogenesis in human MSC from bone marrow. Therefore, highly antioxidant by-products like D6 may represent a relevant source for development of functional products, for both prevention and treatment of degenerative pathologies associated with aging, like osteoporosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The IFNL4 ss469415590 polymorphism, in high linkage disequilibrium with the IL28B rs12979860 variant, has been associated with hepatitis C virus clearance. We evaluated whether ss469415590 is associated with clinical and immunovirological parameters in human immunodeficiency virus-infected subjects. We found an independent association of the IFNL4 ss469415590 polymorphism with higher prevalence of AIDS-defining illnesses and lower CD4 T cell numbers. These results suggest the existence of common host defence mechanisms against different viral infections., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Novel strategies are necessary to decrease inflammatory parameters in successfully treated HIV-infected patients. Our aim was to evaluate the maintenance of viral suppression and potential changes in inflammatory, immune-activation and coagulation biomarkers in virologically suppressed HIV-infected patients switched to a nucleoside reverse transcriptase inhibitor-sparing (NRTI) and maraviroc (MVC)-containing combined antiretroviral therapy (cART). Fifty-eight HIV-infected patients were observed after their treatment regimens were changed to MVC 150mg/once daily plus ritonavir-boosted protease inhibitor therapy. Activation-, inflammation- and coagulation-associated biomarkers and mitochondrial (mt)DNA were analyzed after a median of 24weeks of follow-up. We observed that after changing to an NRTI-sparing regimen, 96.6% of HIV-patients on viral suppressive cART maintained viral suppression and their CD4+ T cell counts did not change significantly (median of 31weeks of follow-up). This cART switch reduced soluble CD40 ligand (p=0.002), beta-2 microglobulin (p=0.025), and soluble CD14 (p=0.009) in patients with higher baseline levels of these inflammation biomarkers after a median of 24weeks of follow-up. The results of our study show that changing to NRTI-sparing dual therapy decreased the levels of inflammatory biomarkers and maintained the immune-virologic efficacy. The potential benefits of this regimen warrant further investigation to uncover the association of this therapy with the potential decrease in the morbidity and mortality of HIV-infected patients from non-AIDS-defining illnesses., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Levels of soluble CD14 (sCD14) were longitudinally measured in 85 human immunodeficiency virus (HIV)-infected subjects during long-term receipt of suppressive combined antiretroviral therapy (cART) and compared to those in young and elderly HIV-negative control subjects. cART did not normalize sCD14 levels; rather, the HIV-infected group displayed a significantly higher sCD14 level at baseline (ie, before cART initiation), 1 year after cART initiation, and 5 years after cART initiation, compared with both control groups. Furthermore, the baseline CD4(+) T-cell count was inversely associated with the baseline sCD14 level. Our results point to the necessity of complementary therapies to treat the activated/inflamed status associated with chronic HIV infection and to the benefits of early initiation of cART.

Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/β-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n = 151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/β-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year all-cause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.

A case of recurrent cytomegalovirus reactivations in a cytomegalovirus-seropositive woman who received allogeneic cord blood transplantation is described. Thirteen months posttransplantation, her CD3(+) T cell count was extremely low whereas natural killer cells represented 66% of her total lymphocytes. She showed defective thymic function that might contribute to the onset of valganciclovir resistance.

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.

The maraviroc clinical test (MCT) is a clinical approach to establish the indication of maraviroc treatment. In this study, we analysed the long-term outcome of patients receiving a combined antiretroviral therapy (cART) selected according to MCT results. Ninety-two consecutive HIV-infected patients underwent MCT. A virological response (<40 HIV-RNA copies/ml after 24 weeks) was observed in 76/92 patients (82.6%). These patients (n=76) were included in a time to treatment failure analysis; after a mean follow-up period of 88 weeks, treatment failure was confirmed in 14 patients (18.4%). Tropism switch during MCT was observed in 3/35 patients (8.6%); these patients experienced excellent long-term outcome on cART. In conclusion, MCT should be considered as an additional method before CCR5-antagonists prescription., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We analyzed the evolution of viral tropism after 8 days of maraviroc monotherapy, i.e., we used the maraviroc clinical test (MCT), in 21 patients with and 14 without virological response to the drug (MCT(+) and MCT(-) patients, respectively). No increases in CXCR4 inferred viral loads (X4IVLs) were observed in MCT(+) patients, while X4IVLs increased only in MCT(-) patients, with X4IVLs of >2 log(10) HIV RNA copies/ml. These results shed light on the evolution of viral tropism under a CCR5 antagonist in vivo.

Premature immunosenescence has been reported in different HIV scenarios. However, how premature is the HIV-related immunosenescent phenotype is still unknown. Thus, the aim of this study was to analyze the immunosenescent status of young viraemic naive HIV-infected individuals, with less than four years from infection. To this end, replicative senescence, activation and proliferation T-cell levels were analyzed in chronically HIV-infected young individuals and both, elderly and young healthy controls. We show that young HIV-infected viraemic patients, with less than four years from infection, have early immune exhaustion leading to a premature immunosenescence comparable to healthy people 40 years elder. In addition, memory T-cell subsets showed greater alterations than elder healthy controls and, in patients with high viral loads, CD57 expression at the memory T-cell subsets was correlated with lower viral increases but higher CD4 T-cell lost during follow up.

Objectives: to analyze the long-term immunovirological effect and tolerability of a maraviroc-containing antiretroviral therapy in viraemic and pretreated HIV-infected patients with a high prevalence of hepatitis C virus (HCV) coinfection., Methods: forty-six R5 HIV-infected patients (48% HCV-coinfected) started a maraviroc-containing antiretroviral regimen, including patients with multidrug resistant virus and patients after first virologic failure. A retrospective study was performed, analysing percentage of patients with undetectable viral load, mean CD4+ gain, liver enzymes, clinical events and treatment modification up to week 48., Results: Raltegravir plus a boosted protease inhibitor was combined with maraviroc in 65.2% of the patients (mainly patients with multidrug resistant virus), while the coformulation lamivudine/abacavir was combined with maraviroc in 26.1% (all of them patients after first virologic failure). After 48 weeks on maraviroc-containing regimen, 96.3% of the patients had achieved undetectability and a mean CD4+ count increase of 151 cells/mm3 was observed. Liver enzymes did not increase along the follow up. One patient died after 24 weeks follow up due to heroin overdose. One patient developed a non-Hodgkin lymphoma after 36 weeks follow up, despite undetectable viral load and significant CD4+ increase was achieved (the only AIDS-defining event observed). Treatment modification was performed in 19.6% of the patients: 77.7% of them experienced a treatment simplification and only 1/46 suspended maraviroc., Conclusions: maraviroc-containing regimen is long-term effective and well tolerated in HIV-infected patients in routine clinical practice and in different clinical scenarios.