Atazanavir-Based Therapy Is Associated with Higher Hepatitis C Viral Load in HIV Type 1-Infected Subjects with Untreated Hepatitis C

Comunicación cortaWe assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9-6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1 (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients

Different HCV exposure drives specific miRNA profile in PBMCS of HIV patients

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM"Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV-(n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.This work has been supported by grants from Institute of Health Carlos III, [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander [grant number 1.010.932 to AFR] and the Spanish AIDS Research Network (RD16CIII/0002/0002), and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) [CP14/CIII/00010 and CPII20CIII/0001]

NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins

Artículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMIncreased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targetsI.T. was supported by Fomento de Investigación and FPI-UAM fellowships by Universidad Autónoma de Madrid. E.M.G. and I.T. were funded by PID2021-127899OB-I00 Generación de Conocimiento and CNS2023-144841 consolidación investigadora grants from Agencia Estatal de Investigación. E.M.G. and C.D.A. were also supported by RYC2018-024374-I. Ramón y Cajal Program. E.M.G., M.J.B., and M.G. were supported by REDINCOV by la MARATÓ TV3 (202104-30-31) and La Caixa Foundation HR20-00218. E.M.G., I.S. and I.S.C. were funded by CIBERINFECC from Instituto de Salud Carlos III. O.P. was supported by REDINCOV. MCM was supported by La Caixa Banking Foundation LCF/PR/HR20-00218. IGA was from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER). I.S.C. was supported by the Rio Hortega Grant program (CM21/00157) and CIBERINFECC from Instituto de Salud Carlos III. F.S.M., A.A. were supported by INMUNOVACTER REACTEU grant from Comunidad de Madrid. F.S.M. was also supported by grants PDC2021-121719-I00 and PID-2020-120412RB-I00 from the Spanish Ministry of Economy and competitiveness (MINECO). M.J.B. is supported by the Agencia Estatal de Investigación project PID2021-123321OB-I00 funded by MCIN /AEI /10.13039/ 501100011033/ FEDER, UE; the Gilead Fellowship GLD22/00152, and the Miguel Servet program funded by the Spanish Health Institute Carlos III (CPII22/00005). N.M.C. was supported by S2022/BMD7209 (INTEGRAMUNE-CM) to N.M.C. C.M.C. was supported by FIS.18/01163. F.S.M. and N.M.C. were also supported by La Caixa Health Research Grant LCF/PR/HR23/52430018. Grants to A.A. from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III, co-funded by the Fondo Europeo de Desarrollo Regional (FEDER) (FIS PI19/00549; FIS PI22/01542), and Sociedad Cooperativa de Viviendas Buen Suceso, S. Coop. Mad; to A.A. and F.S.M. from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional (FEDER) (CIBER Cardiovascular). A.A. was supported by CIBER cardiovascular (CIBERCV) from Instituto de Salud Carlos III. L.E.P. was financed by Inmunovacter REACT-UE (Comunidad de Madrid). We also would like to thank Verónica Labrador from the Microscopy Core from Centro Nacional de Investigaciones Cardiovasculares for technical support in confocal image analysi

Randomized trial evaluating the neurotoxicity of dolutegravir/abacavir/lamivudine and Its reversibility after switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide: GESIDA 9016

Background: Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. Methods: We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. Results: Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. Conclusions: Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAFThis work was funded through a grant from Gilead Sciences made to the SEIMC-GESIDA Foundation (IN-ES-292-2119

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Desarrollo de recursos didácticos adaptados para la Generación Z en el ámbito de la Ingeniería Química

En este Proyecto Innova-docencia se van a elaborar una serie de recursos didácticos que sirvan de apoyo a la docencia presencial y virtual de asignaturas del área de la Ingeniería Química a nivel de Grado y de Máster enfocados a la Generación Z

Análisis de las células NK en la infección por el virus de la inmunodeficiencia humana y su relación con la progresión de la enfermedad

Tesos doctoral inédita. Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 19 de Noviembre de 199

Analisis de las celulas NK en la infeccion por el virus de la inmunodeficiencia humana y su relacion con la progresion de la enfermedad

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai