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The clinical and epidemiological implications of abnormal immune responses in COVID-19 for latent tuberculosis infection (LTBI) screening are unclear.We reviewed QuantiFERON TB Gold Plus (QFT-Plus) results (36,709 patients) from July 2016 until October 2021 in Asturias (Spain). We also studied a cohort of ninety hospitalized patients with suspected/confirmed COVID-19 pneumonia and a group of elderly hospitalized patients with COVID-19 who underwent serial QFT-Plus and immune profiling testing.The indeterminate QFT-Plus results rate went from 1.4% (July 2016 to November 2019) to 4.2% during the COVID-19 pandemic. The evolution of the number of cases with low/very low interferon-gamma (IFN-gamma) response in the mitogen tube paralleled the disease activity and number of deaths during the pandemic waves in our region (from March 2020 to October 2021). The percentages of positive QFT-plus patients did not significantly change before and during the pandemic (13.9%Low IFN-gamma responses in mitogen tube of QFT-Plus often occur in COVID-19 pneumonia, which is associated with a low number of an effector CD8 + T-cell subset and does not seem to affect LTBI screening; however, this abnormality seems to parallel the dynamics of COVID-19 at the population level and its mortality.

To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART.We included adults aged 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route.Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA 5 logThe rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA 5 log

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts. This study has been partially supported by the Spanish Ministry of Science and Innovation within the DOTTHEALTH Project (MCI/AEI/FEDER, UE) under Grant PID2019-106942RB-C32, the OBSER-MENH Project (MCIN/AEI/10.13039/501100011033 and UE (“NextGenerationEU”/PRTR)) under Grant TED2021-130398B-C21 and the project RAICES (IMIENS 2022), PI18CIII/00004 “Infobanco para uso secundario de datos basado en estándares de tecnología y conocimiento: implementación y evaluación de un infobanco de salud para CoRIS (Info-bank for the secondary use of data based on technology and knowledge standards: implementation and evaluation of a health info-bank for CoRIS) - SmartPITeS” and PI18CIII/00019 - PI18/00890 - PI18/00981 “Arquitectura normalizada de datos clínicos para la generación de infobancos y su uso secundario en investigación: solución tecnológica (Clinical data normalized architecture for the generation of info-banks and their secondary use in research: technological solution) - CAMAMA 4” from Fondo de Investigación Sanitaria (FIS) Plan Nacional de I+D+i. The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and co-financed by ISCIII-Subdirección General de Evaluación and el Fondo Europeo de Desarrollo Regional (FEDER). The list of members of the Cohort of the Spanish HIV Research Network (CoRIS) is included in the Supplementary Material. Additional relationships between HIV-related diseases confirmed or discarded are included as Supplementary Material. This study would not have been possible without the collaboration of all patients, medical and nursing staff and data mangers who have taken part in the Project. Sí

Objectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA

Introduction Infective endocarditis (IE) still carries high morbidity and mortality and frequently requires surgery. The benefit of mitral valve repair (MVr) in the setting of IE is yet to be proven. The goal of this study was to assess the results of MVr in patients with IE after a minimum follow-up of 1 year. Methods This study is based on a Spanish nationwide prospective registry that included patients operated on for native mitral valve IE. The collaborating Institutions pooled their pre-, peri-, and postoperative data into the database of the GAMES group [Grupo de Apoyo al Manejo de la EndocarditiS (Group for support and management of infective endocarditis)]. Results Data from 27 hospitals were recorded and 3524 cases of active IE identified between 2008 and 2016. There were 1513 cases of mitral IE, of which 898 involved native valves. Of these, 437 patients underwent surgical treatment, and 369 completed the 1-year follow-up. The valve was repaired in 68 cases (18.4%). Preoperative groups were comparable (EuroSCORE MVr 7.7 vs MVR 8.0; p = ns). Mortality in the repair group was inferior to that in the replacement group (16.2% vs 27.2%, p = 0.058). At 1 year, mortality remained higher in the replacement group: 3.7% vs 2.9%. Relapse of the infection was slightly more frequent in the repair group (7.1% vs 3.7%; p = ns), although this did not lead to higher rates of reintervention (MVr/MVR: 2.9% vs 4.9%). Conclusion MVr is an attractive option for specific patients with IE and does not seem to negatively impact on relapses.

For the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) investigators: Hospital Costa del Sol, Marbella: Fernando Fernández Sánchez, Mariam Noureddine, Gabriel Rosas, Javier de la Torre Lima. Hospital Universitario de Cruces, (Bilbao): Roberto Blanco, María Victoria Boado, Marta Campaña Lázaro, Alejandro Crespo, Josune Goikoetxea, José Ramón Iruretagoyena, Josu Irurzun Zuazabal, Leire López-Soria, Miguel Montejo, Javier Nieto, David Rodrigo, Regino Rodríguez, Yolanda Vitoria, Roberto Voces. Hospital Universitario Virgen de la Victoria, Málaga: María (Mª) Victoria García López, Radka Ivanova Georgieva, Guillermo Ojeda, Isabel Rodríguez Bailón, Josefa Ruiz Morales. Hospital Universitario Donostia-Policlínica Gipuzkoa, San Sebastián: Ana María Cuende, Tomás Echeverría, Ana Fuerte, Eduardo Gaminde, Miguel Ángel Goenaga, Pedro Idígoras, José Antonio Iribarren, Alberto Izaguirre Yarza, Xabier Kortajarena Urkola, Carlos Reviejo. Hospital General Universitario de Alicante, Alicante: Rafael Carrasco, Vicente Climent, Patricio Llamas, Esperanza Merino, Joaquín Plazas, Sergio Reus. Complejo Hospitalario Universitario A Coruña, A Coruña: Nemesio Álvarez, José María Bravo-Ferrer, Laura Castelo, José Cuenca, Pedro Llinares, Enrique Miguez Rey, María Rodríguez Mayo, Efrén Sánchez, Dolores Sousa Regueiro. Complejo Hospitalario Universitario de Huelva, Huelva: Francisco Javier Martínez. Hospital Universitario de Canarias, Canarias: Mª del Mar Alonso, Beatriz Castro, Dácil García Rosado, Mª del Carmen Durán, Mª Antonia Miguel Gómez, Juan Lacalzada, Ibrahim Nassar. Hospital Regional Universitario de Málaga, Málaga: Antonio Plata Ciezar, José Mª Reguera Iglesias. Hospital Universitario Central Asturias, Oviedo: Víctor Asensi Álvarez, Carlos Costas, Jesús de la Hera, Jonnathan Fernández Suárez, Lisardo Iglesias Fraile, Víctor León Arguero, José López Menéndez, Pilar Mencia Bajo, Carlos Morales, Alfonso Moreno Torrico, Carmen Palomo, Begoña Paya Martínez, Ángeles Rodríguez Esteban, Raquel Rodríguez García, Mauricio Telenti Asensio. Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona: Manuel Almela, Juan Ambrosioni, Manuel Azqueta, Mercè Brunet, Marta Bodro, Ramón Cartañá, Carlos Falces, Guillermina Fita, David Fuster, Cristina García de la Mària, Laura García-Valls, Marta Hernández-Meneses, Jaume Llopis Pérez, Francesc Marco, José M. Miró, Asunción Moreno, David Nicolás, Salvador Ninot, Eduardo Quintana, Carlos Paré, Daniel Pereda, Juan M. Pericás, José L. Pomar, José Ramírez, Irene Rovira, Elena Sandoval, Marta Sala, Marta Sitges, Dolors Soy, Adrián Téllez, José M. Tolosana, Bárbara Vidal, Jordi Vila. Hospital General Universitario Gregorio Marañón, Madrid: Iván Adán, Javier Bermejo, Emilio Bouza, Daniel Celemín, Gregorio Cuerpo Caballero, Antonia Delgado Montero, Ana Fernández Cruz, Ana García Mansilla, Mª Eugenia García Leoni, Víctor González Ramallo, Martha Kestler Hernández, Amaia Mari Hualde, Mercedes Marín, Manuel Martínez-Sellés, Mª Cruz Menárguez, Patricia Muñoz, Cristina Rincón, Hugo Rodríguez-Abella, Marta Rodríguez-Créixems, Blanca Pinilla, Ángel Pinto, Maricela Valerio, Pilar Vázquez, Eduardo Verde Moreno. Hospital Universitario La Paz, Madrid: Isabel Antorrena, Belén Loeches, Alejandro Martín Quirós, Mar Moreno, Ulises Ramírez, Verónica Rial Bastón, María Romero, Araceli Saldaña. Hospital Universitario Marqués de Valdecilla, Santander: Jesús Agüero Balbín, Carlos Armiñanzas Castillo, Ana Arnaiz, Francisco Arnaiz de las Revillas, Manuel Cobo Belaustegui, María Carmen Fariñas, Concepción Fariñas-Álvarez, Rubén Gómez Izquierdo, Iván García, Claudia González Rico, Manuel Gutiérrez-Cuadra, José Gutiérrez Díez, Marcos Pajarón, José Antonio Parra, Ramón Teira, Jesús Zarauza. Hospital Universitario Puerta de Hierro, Madrid: Fernando Domínguez, Pablo García Pavía, Jesús González, Beatriz Orden, Antonio Ramos. Hospital Universitario Ramón y Cajal, (Madrid): Tomasa Centella, José Manuel Hermida, José Luis Moya, Pilar Martín-Dávila, Enrique Navas, Enrique Oliva, Alejandro del Río, Jorge Rodríguez-Roda Stuart, Soledad Ruiz Rodríguez. Hospital Universitario Virgen de las Nieves, Granada: Carmen Hidalgo Tenorio. Hospital Universitario Virgen Macarena, Sevilla: Manuel Almendro Delia, Omar Araji, José Miguel Barquero, Román Calvo Jambrina, Marina de Cueto, Juan Gálvez Acebal, Irene Méndez, Isabel Morales, Luis Eduardo López-Cortés. Hospital Universitario Virgen del Rocío, Sevilla: Arístides de Alarcón, Emilio García, Juan Luis Haro, José Antonio Lepe, Francisco López, Rafael Luque. Hospital San Pedro, Logroño: Luis Javier Alonso, Pedro Azcárate, José Manuel Azcona Gutiérrez, José Ramón Blanco, Lara García-Álvarez, José Antonio Oteo, Mercedes Sanz. Hospital de la Santa Creu i Sant Pau, Barcelona: Natividad de Benito, Mercé Gurguí, Cristina Pacho, Roser Pericas, Guillem Pons. Complejo Hospitalario Universitario de Santiago de Compostela, A Coruña: M. Álvarez, A. L. Fernández, Amparo Martínez, A. Prieto, Benito Regueiro, E. Tijeira, Marino Vega. Hospital Santiago Apóstol, Vitoria: Andrés Canut Blasco, José Cordo Mollar, Juan Carlos Gainzarain Arana, Oscar García Uriarte, Alejandro Martín López, Zuriñe Ortiz de Zárate, José Antonio Urturi Matos. Hospital SAS Línea de la Concepción, Cádiz: Gloria García Domínguez, Antonio Sánchez-Porto. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia: José Mª Arribas Leal, Elisa García Vázquez, Alicia Hernández Torres, Ana Blázquez, Gonzalo de la Morena Valenzuela. Hospital de Txagorritxu, Vitoria: Ángel Alonso, Javier Aramburu, Felicitas Elena Calvo, Anai Moreno Rodríguez, Paola Tarabini-Castellani. Hospital Virgen de la Salud, Toledo: Eva Heredero Gálvez, Carolina Maicas Bellido, José Largo Pau, Mª Antonia Sepúlveda, Pilar Toledano Sierra, Sadaf Zafar Iqbal-Mirza. Hospital Rafael Méndez, Lorca-Murcia: Eva Cascales Alcolea, Pilar Egea Serrano, José Joaquín Hernández Roca, Ivan Keituqwa Yañez, Ana Peláez Ballesta, Víctor Soriano. Hospital Universitario San Cecilio, Granada: Eduardo Moreno Escobar, Alejandro Peña Monje, Valme Sánchez Cabrera, David Vinuesa García. Hospital Son Llátzer, Palma de Mallorca: María Arrizabalaga Asenjo, Carmen Cifuentes Luna, Juana Núñez Morcillo, Mª Cruz Pérez Seco, Aroa Villoslada Gelabert. Hospital Universitario Miguel Servet, Zaragoza: Carmen Aured Guallar, Nuria Fernández Abad, Pilar García Mangas, Marta Matamala Adell, Mª Pilar Palacián Ruiz, Juan Carlos Porres. Hospital General Universitario Santa Lucía, Cartagena: Begoña Alcaraz Vidal, Nazaret Cobos Trigueros, María Jesús Del Amor Espín, José Antonio Giner Caro, Roberto Jiménez Sánchez, Amaya Jimeno Almazán, Alejandro Ortín Freire, Monserrat Viqueira González. Hospital Universitario Son Espases, Palma de Mallorca: Pere Pericás Ramis, Mª Ángels Ribas Blanco, Enrique Ruiz de Gopegui Bordes, Laura Vidal Bonet. Complejo Hospitalario Universitario de Albacete, Albacete: Mª Carmen Bellón Munera, Elena Escribano Garaizabal, Antonia Tercero Martínez, Juan Carlos Segura Luque., [Background] Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). [Methods] Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008–2012) was performed. [Results] A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56–76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P < .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04–1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09–.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22–.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. [Conclusions] OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded., This work was supported by the Ministerio de Economia and Competitividad (Madrid, Spain) (FIS NCT00871104, Instituto de Salud Carlos III). J. M. P. received a “Rio Hortega” research grant from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad (Madrid, Spain) and the European Society for Clinical Microbiology and Infectious Diseases and Federation of European Microbiological Societies Research Fellowship 2016. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Madrid, Spain) provided J. M. M. with a personal intensification research grant (INT15/00168) during 2016 and a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Pi i Sunyer for the period 2017–2019.

Background To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45–60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45–50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38–6.55 and 2.63; 1.44–4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13–4.14) and urogenital symptoms (2.54; 1.42–4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74–13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

© The Author(s) 2020., [Background]: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS)., [Methods]: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL), [Results]: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL, [Conclusions]: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads., The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I+D+i and cofnanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER)”.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/mu L. HIV-RNA was

Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer).

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population.We conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs.Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.

[Objectives]: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004–2017., [Methods]: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models., [Results]: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL., [Conclusions]: The initial assessment of HIV‐infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations., The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/ 0017/0018 and RD16/0002/0006) as part of the Plan Nacional I+D+i and cofinanced by ISCIII-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER).

[EN]: [Introduction]: Our aims were to investigate the adherence to national guidelines of initial antiretroviral therapy (ART) in the Spanish multicenter CoRIS cohort during the years 2010–2015, to identify the reasons for the prescription of nonrecommended treatments, and to explore the role of institutional constraints to guideline compliance. [Methods]: ART regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Physicians were asked the reasons for prescribing nonrecommended regimens. Factors associated with the prescription of non recommended regimens were assessed using multivariable logistic regression. [Results]: During the study period, 586 (10.7%) of 5479 patients who started ART were given a regimen not recommended in the guidelines. The most frequent reasons for prescribing nonrecommended regimens were: enrolment in clinical trials (43.3%), comorbidities and/or interactions (10.2%), pregnancy (8.7%), and cost (7.7%). Among 37 participating centers, 16 (43%), treating 3561 patients, reported limitations related with the cost of ART, and 20 (54%), treating 1365 patients, reported restrictions for prescribing at least one recommended antiretroviral. In multivariable analysis, a higher risk of receiving nonrecommended regimens was associated with male gender, HIV acquisition by heterosexual transmission, low viral loads, initiation of treatment during the years 2011 to 2015, and initiation of treatment in a center with restricted access to at least one antiretroviral drug. [Conclusions]: Compliance to clinical guidelines was high. A high proportion of centres reported cost limitations for ART or restricted access to at least one recommended antiretroviral drug, with a significant impact on the choice of initial regimens., [ES]: [Introducción]: Nuestros objetivos fueron investigar la adecuación del tratamiento antirretroviral (TAR) inicial a las guías nacionales en la cohorte multicéntrica española CoRIS durante los años 2010-2015, identificar las razones para la prescripción de pautas no recomendadas y estudiar la influencia de limitaciones institucionales en el cumplimiento de las guías. [Métodos]: Se clasificaron las pautas de TAR en recomendadas, alternativas o no recomendadas según las guías de GeSIDA/Plan Nacional sobre el sida. Se preguntaron las razones para haber prescrito pautas no recomendadas a los médicos prescriptores. Se evaluaron los factores asociados a la prescripción de pautas no recomendadas mediante regresión logística multivariable. [Resultados]: Durante el periodo de estudio 586 (10,7%) de 5.479 pacientes que iniciaron TAR recibieron una pauta no recomendada. Las razones más frecuentes para prescribir pautas no recomendadas fueron: participación en ensayo clínico (43,3%), comorbilidades y/o interacciones (10,2%), embarazo (8,7%) y coste (7,7%). Entre los 37 centros participantes 16 (43%), que incluían 3.561 pacientes, referían limitaciones en el coste del TAR y 20 (54%), que incluían 1.365 pacientes, referían restricciones para la prescripción de al menos un fármaco recomendado. En el análisis multivariable el riesgo de recibir una pauta no recomendada se asoció a ser varón, adquisición del VIH por vía heterosexual, carga viral baja, inicio del tratamiento durante los años 2011 a 2015 e inicio del tratamiento en un centro con acceso restringido al menos a un antirretroviral. [Conclusiones]: El cumplimiento de las guías de TAR fue elevado. Una alta proporción de centros refirieron limitaciones de coste para el TAR o acceso restringido al menos a uno de los fármacos antirretrovirales recomendados; esto último influyó en la elección de pautas no recomendadas.

OBJECTIVES We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (NRTI), and 1 drug from another family. Four of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further 6 regimens, which are based on an INSTI, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with cobicistat or ritonavir (PI/COBI, PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include 3 (or at least 2) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART).We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure.Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200-499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE.In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.

Background: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions. Objectives: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions. Methods: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89). Results: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients. Conclusions: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered. Sin financiación 18.639 JCR (2018) Q1, 3/136 Cardiac & Cardiovascular Systems 9.280 SJR (2018) Q1, 1/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

ObjectivesContemporary data from country-wide cohorts are needed to reveal trends in the occurrence of acute myocardial infarction (AMI) in people living with HIV (PLWH). We analysed time trends in the standardized incidence rate (sIR) of AMI in PLWH in Spain from 2004 to 2015, and compared them with trends in the general population. MethodsA longitudinal study in a nationwide contemporary multicentre HIV-infected cohort was carried out. Data on all incident AMI events were collected, and age- and sex-standardized IRs calculated. To analyse the IR of AMI in the general population, the national rates of hospital discharges for AMI per 100000 inhabitants stratified for age and sex from 2004 to 2015 were obtained using the morbidity report data from the National Statistics Institute. A Poisson regression model was fitted to assess the effect of covariates of interest on AMI occurrence. ResultsThe sIRs of AMI in 2004-2015 were 237.92 [95% confidence interval (CI) 225.95-249.90] and 66.75 (95% CI: 23.49-110.01) per 100000 patient-years in male and female PLWH, respectively. There was a decrease in the sIR of AMI in male PLWH from 279.02 (95% CI: 265.46-292.59) per 100000person-years in 2004-2009 to 222.13 (95% CI: 210.83-233.42) per 100000 person-years in 2010-2015. Compared with the general population, the sIR ratio was 1.41 (95% CI: 1.26-1.55) in 2004-2009, and 1.28 (95% CI: 1.15-1.43) in 2010-2014. AMI occurrence was associated with older age (P350 cells/L compared with the 0-100 cells/L stratum), and the period 2004-2009 (P

Summary Background Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir–ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. Methods In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. Findings Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI −5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3–4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). Interpretation In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. Funding Bristol Myers-Squibb and Fundacion SEIMC-GESIDA.

Cohorte de la Red de InvestigacioÂn en Sida (CoRIS)., [Objetives] Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013., [Design] Prospective multicenter cohort study., [Methods] Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced (“NAE development”); from alive and NAE-experienced to death (“Death after NAE”); and from alive and NAE-free to death (“Death without NAE”). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition “Death after NAE”., [Results] 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80–30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition “Death after NAE” was 12.1 (95%CI, 4.90–29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45–6.57) for intermediate-severity; and 9.85 (5.45–17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11–3.84), age>50 years (1.78, 1.08–2.94), hepatitis C-coinfection (2.52, 1.38–4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20–5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01–4.66 for CD4 cell count between 200–350, both compared to CD4 cell count higher than 500) and concomitant CD4, [Conclusion] NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts., This work was supported by the RD12/0017/0023 and RD 16/0025/0038 projects as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), FIS (PI08/893), FIS (PI13/02256), FIS (PI16/01740), FISABIO UGP-14-197, Contrato de Intensificación de la Actividad Investigadora INT 14/00207, Contrato Predoctotal FISABIO 2015 (UGP-15-152) and Contrato Río Hortega (CM15/00187).

The aim of the study was to draw a comparison between the characteristics of infective endocarditis (IE) in patients with cancer and those of IE in noncancer patients.Patients with IE, according to the modified Duke criteria, were prospectively included in the GAMES registry between January 2008 and February 2014 in 30 hospitals. Patients with active cancer were compared with noncancer patients.During the study period, 161 episodes of IE fulfilled the inclusion criteria. We studied 2 populations: patients whose cancer was diagnosed before IE (73.9%) and those whose cancer and IE were diagnosed simultaneously (26.1%). The latter more frequently had community-acquired IE (67.5% vs 26.4%, P

Objectives We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. Methods CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naive at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. Results In total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01–15.15] and 7.06 (95% CI 5.45–9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28–0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94; 95% CI 1.21–3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving 4 years of ART was 0.72 (95% CI 0.36–1.44), 0.10 (95% CI 0.04–0.25) and 0.05 (95% CI 0.01–0.17), respectively, compared with ART-naive patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. Conclusions The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens.

Background The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. Methods miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms. Results A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response. Conclusions Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.

Objectives The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean (LAC) or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP). Methods The Cohort of the Spanish AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naive patients representing 13 of the 17 Spanish regions. The study period was 2004–2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. Results Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio (OR) 2.0 (95% confidence interval (CI) 1.5–2.8) and OR 1.7 (95% CI 1.4–2.1), respectively], as did LAC aged 35–50 years [OR 1.3 (95% CI 1.0–1.6)]. There were no major differences in time to antiretroviral therapy (ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [OR 0.8 (95% CI 0.7–1.0) and OR 0.7 (95% CI 0.6–0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [OR 2.0 (95% CI 1.1–3.7) and OR 1.6 (95% CI 1.1–2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. Conclusions Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis.

Objectives To compare causes of death (CoDs) from two independent sources: National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research cohort [Cohort de adultos con infeccion por VIH de la Red de Investigacion en SIDA CoRIS)] and compare the two coding algorithms: International Classification of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death in HIV (revised CoDe). Methods Between 2004 and 2008, CoDs were obtained from the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies, infections, cardiovascular, blood disorders, pulmonary, central nervous system, drug use, external, suicide, other causes and ill defined. Results There were 160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the two sources and in 115 (72%) cases for the two coding algorithms. According to revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%) and liver related (9%), these percentages were similar, 57, 10 and 8%, respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70% due to liver-related, infections and ill-defined causes being coded as HIV/AIDS. Conclusion There is substantial variation in CoDs in HIV-infected persons according to sources and algorithms. ICD-10 in patients known to be HIV-positive overestimates HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined causes. CoDe seems as the best option for cohort studies.

Background The aim of this study was to analyse associations between educational level and delayed HIV diagnosis (DD), late initiation of combined antiretroviral therapy (cART), overall and in subjects with timely HIV diagnosis, virological and immunological responses to cART, and mortality from HIV diagnosis and cART initiation. Methods This was a multicentre cohort study of HIV-positive treatment-naive subjects in Spain between 2004–2009. Logistic and Cox regression analyses were used. Results Of 4,549 subjects, 44.5% had low education level (LOW), 34.4% medium education level (MED) and 21.1% high education level (HIG). In men, DD was more common in MED (OR 1.3 [95% CI 1.0, 1.7]) or LOW [OR 1.8 (95% CI 1.4, 2.3)] compared to HIG. In women, the opposite was observed; women with HIG were 40% more likely to have DD than those with LOW (OR 1.4 [95% CI 0.8, 2.5]). In individuals with timely HIV diagnoses, percentages of late cART initiators were similar (LOW 9.5%, MED 11.4% and HIG 7.0%; P=0.114). Immunological (LOW 68%, MED 76% and HIG 84%) and virological (LOW 76%, MED 83% and HIG 86%) responses to cART increased significantly with educational level; these increases remained significant in multivariate analyses. Mortality for LOW subjects was higher than for HIG, from HIV diagnosis (hazard ratio [HR] 2.3 [95% CI 1.1, 4.9]) and from cART initiation (HR 1.8 [95% CI 0.8, 3.9]). Conclusions We found important differences by educational level in diagnosis delay, virological and immunological responses to cART and mortality in a country with universal health care. Women with high educational level are at higher risk of having delayed HIV diagnoses. Educational level should be taken into account when designing HIV testing and clinical management strategies.

SUMMARYTo analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (PP=0·02). There were differences in the groups regarding the CD4 response (P=0·01), but not the virological response (P=0·4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0·01), viral load at 12 months (P=0·0006), poorer adherence to therapy of injecting drug users (IDUs)vs. each of the other groups (Pvs. heterosexual (P=0·003) and men who have sex with men (MSM) groups (P=0·02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

The prevalence of injection drug use decreased from 67.3% in 1997 to 14.5% in 2006 among Spanish patients infected with human immunodeficiency virus (HIV). A parallel decrease in the prevalence of coinfection with hepatitis C virus was observed, from 73.8% in 1997 to 19.8% in 2006. This steady decrease in the prevalence of coinfection among Spanish patients was caused by a change in transmission routes of HIV infection.

BACKGROUND The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. METHODS We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of or =5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of

This study was partially financed by the CIBER de Enfermedades Respiratorias (CIBERES) from the ISCIII (CB06/06/0058) and by Fundación BBVA-FundacioóCarolina (research fellowship of Maricela Valerio)., Muñoz, P; Kestler, M; De Alarcon, A; Miro, JM; Bermejo, J; Rodriguez-Abella, H; Farinas, MC; Belaustegui, MC; Mestres, C; Llinares, P; Goenaga, M; Navas, E; Oteo, JA; Tarabini, P; Bouza, E.

OBJECTIVES: We aim to describe rates and risk factors of Hepatitis C Virus (HCV) diagnoses, follow-up HCV testing and HCV seroconversion from 2004-2011 in a cohort of HIV-positive persons in Spain. METHODS: CoRIS is a multicentre, open and prospective cohort recruiting adult HIV-positive patients naïve to antiretroviral therapy. We analysed patients with at least one negative and one follow-up HCV serology. Incidence Rates (IR) were calculated and multivariate Poisson regression was used to estimate adjusted Rates Ratios (aIRR). RESULTS: Of 2112 subjects, 53 HCV diagnoses were observed, IR = 0.93/100 py (95%CI: 0.7-1.2). IR increased from 0.88 in 2004-05 to 1.36 in 2010-11 (aIRR = 1.55; 95%CI: 0.37-6.55). In men who have sex with men (MSM) from 0.76 to 1.10 (aIRR = 1.45; 95%CI: 0.31-6.82); in heterosexual (HTX) subjects from 1.19 to 1.28 (aIRR = 1.08; 95%CI: 0.11-10.24). HCV seroconversion rates decreased from 1.77 to 0.65 (aIRR = 0.37; 95%CI: 0.12-1.11); in MSM from 1.06 to 0.49 (aIRR = 0.46; 95%CI: 0.09-2.31); in HTX from 2.55 to 0.59 (aIRR = 0.23; 95%CI: 0.06-0.98). HCV infection risk was higher for injecting drug users (IDU) compared to HTX (aIRR = 9.63;95%CI: 2.9-32.2); among MSM, for subjects aged 40-50 compared to 30 or less (IRR = 3.21; 95%CI: 1.7-6.2); and among HTX, for female sex (aIRR = 2.35; 95%CI: 1.03-5.34) and

To describe tuberculosis (TB) incidence, risk factors, clinical presentation, disease management and outcomes in human immunodeficiency virus (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010.Open multicentre cohort of antiretroviral treatment (ART) naïve patients at entry. Incidence and risk factors were evaluated using multivariate Poisson regression.Among 6811 patients, 271 were eligible for the study and 198 for the estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000 person-years. TB was associated with low education level (rate ratio [RR] 2.65, 95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45), heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI 1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4200 cells/mm(3) (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02) or5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were previously treated cases; 175 (65%) were bacteriologically confirmed. Drug susceptibility testing was performed in 146 (83%) patients: resistance to first-line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti-tuberculosis treatment with four or three drugs was prescribed in respectively 55% and 36% of cases. Treatment default was 11%, and was higher among previously treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new and 50% of previously treated cases were cured or completed treatment, and 18 (6.6%) died.TB incidence in HIV-infected patients remains high. Interventions should include early HIV diagnosis and access to ART, enhanced bacteriological confirmation, wider use of four-drug regimens and reduction in treatment default.

In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is500cells/μL; if the CD4(+) lymphocyte count is500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL)10(5)copies/mL, CD4(+) lymphocyte percentage14%, cognitive impairment, and age55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined.

The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with

HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected.

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases

Background The collection of samples from HIV-infected patients is the beginning of the chain of translational research. To carry out quality research that could eventually end in a personalized treatment for HIV, it is essential to guarantee the availability, quality and traceability of samples, under a strict system of quality management. Methods The Spanish HIV BioBank was created with the objectives of processing, storing and providing distinct samples from HIV/AIDS patients, categorized according to strictly defined characteristics, free of charge to research projects. Strict compliance to ethical norms is always guaranteed. Results At the moment, the HIV BioBank possesses nearly 50,000 vials containing different prospective longitudinal study sample types. More than 1,700 of these samples are now used in 19 national and international research projects. Conclusion The HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working on HIV, but also for those groups trying to establish large networks focused on research on specific clinical problems. It also represents a model to stimulate cooperative research among large numbers of research groups working as a network on specific clinical problems. The main objective of this article is to show the structure and function of the HIV BioBank that allow it to very efficiently release samples to different research project not only in Spain but also in other countries.

To evaluate the satisfaction with self-injected enfuvirtide (ENF) and the clinical outcome of HIV-infected patients without very advanced disease.ESPPE is a multicenter observational study that included 103 evaluated patients showing baseline characteristics predictive of positive outcome: CD4100 cells/mm3, viral load (VL)100,000 copies/mL, previous treatment with a maximum of 10 antiretroviral drugs, and concomitant use of 2 active drugs. By using validated surveys, patients were questioned 6 months after the prescription of ENF about their quality of life (QoL) and acceptance of self-injections and adherence to the treatment.At 6 months, the mean CD4 increase was 121 cells/mm3 (p.05) and 65% (intent-to-treat, ENF stopped=failure) had VL50 copies/mL (p.001). Fourteen patients discontinued the treatment, mostly due to intolerance (6). The majority (89%) assessed all items relating QoL as "excellent," "very good," or "good." The treatment satisfaction index on a visual analog scale scored a median of 8.1 out of 10; when participants were asked about the interference of injections on their daily activities, 87% answered "never" or "only sometimes."Effectiveness and patients' perception about ENF remain good when ENF was used in patients without very advanced disease. QoL was not impaired after ENF use.

Objective This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. Methods To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. Results In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: 500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). Conclusions These new guidelines updates previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated.