34 results on '"Nuria Espinosa"'
Search Results
2. Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program
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Karin Neukam, Cristina Roca, Pompeyo Viciana, Luis F. López-Cortés, Yusnelkis Milanés Guisado, Nuria Espinosa, María Fontillón, Ana Domínguez Castaño, and Cesar Sotomayor
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Adult ,Male ,medicine.medical_specialty ,HIV Infections ,Efficiency, Organizational ,Rate ratio ,Men who have sex with men ,Cohort Studies ,Sexual and Gender Minorities ,Risk Factors ,Internal medicine ,Humans ,Mass Screening ,Outpatient clinic ,Medicine ,Neoplasm Staging ,business.industry ,Incidence ,Incidence (epidemiology) ,Gastroenterology ,Anal Squamous Cell Carcinoma ,HIV ,General Medicine ,Middle Aged ,Anus Neoplasms ,Confidence interval ,Spain ,Case-Control Studies ,Cohort ,Carcinoma, Squamous Cell ,Female ,business ,Follow-Up Studies ,Cohort study - Abstract
Anal squamous cell carcinoma is rare, in general, but considerably higher in HIV-infected men who have sex with men. There is no consensus on the screening of at-risk populations.This study aimed to determine the incidence rates of anal squamous cell carcinoma and the efficacy of a screening program.This is a cohort study (SeVIHanal/NCT03713229).This study was conducted at an HIV outpatient clinic in Seville, Spain.From 2004 to 2017, all patients with at least 1 follow-up visit were analyzed (follow-up group), including a subgroup of men who have sex with men who participated in a specialized program for screening and treating anal neoplasia (SCAN group) from 2011 onward.The primary outcome measure was the incidence rate of anal squamous cell carcinoma.Of the 3878 people living with HIV included in the follow-up group, 897 were transferred to the SCAN group; 1584 (41%) were men who have sex with men. Total follow-up was 29,228 person-years with an overall incidence rate for anal squamous cell carcinoma of 68.4/100,000 person-years (95% CI, 46.7-97.4). The changes in the incidence rate/100,000 person-years (95% CI) over time was 20.7 (3.40-80.5) for 2004 to 2006, 37.3 (13.4-87.3) for 2007 to 2010, and 97.8 (63.8-144.9) for 2011 to 2017 (p0.001). The strongest impact on the incidence of anal squamous cell carcinoma was made by the lack of immune restoration (adjusted incidence rate ratio (95% CI): 6.59 (4.24-10); p0.001), the Centers for Disease Control and Prevention category C (adjusted incidence rate ratio (95% CI): 7.49 (5.69-9.85); p0.001), and non-men who have sex with men (adjusted incidence rate ratio (95% CI): 0.07 (0.05-0.10); p0.001) in a Poisson analysis. From 2010 to 2017, incidence rates (95% CI) of anal squamous cell carcinoma within the SCAN group and the men who have sex with men of the follow-up group were 95.7 (39.6-202) and 201 (101-386)/100,000 person-years (adjusted incidence rate ratio (95% CI): 0.30 (0.23-0.39); p0.001). The incidence rate ratio (95% CI) including non-men who have sex with men in the follow-up group was 0.87 (0.69-1.11); p = 0.269.Adherence to the visits could not be quantified.Incidence rates of anal squamous cell carcinoma in people living with HIV increased significantly from 2004 to 2017, especially in men who have sex with men who were not being screened. Participation in the SCAN program significantly reduced the incidence of anal squamous cell carcinoma in men who have sex with men, in whom focus should be placed, especially on those presenting with Centers for Disease Control and Prevention category C and advanced immune suppression. See Video Abstract at http://links.lww.com/DCR/B734.ANTECEDENTES:El carcinoma anal a células escamosas es generalmente raro, pero considerablemente más alto en hombres infectados por el VIH que tienen relaciones sexuales con hombres. No hay consenso sobre el cribado de poblaciones en riesgo.OBJETIVO:Este estudio tuvo como objetivo determinar las tasas de incidencia del carcinoma anal a células escamosas y la eficacia de un programa de detección.DISEÑO:Estudio de cohorte (SeVIHanal / NCT03713229).AJUSTE:Clínica ambulatoria de VIH en Sevilla, España.PACIENTES:De 2004 a 2017, se analizaron todos los pacientes con al menos una visita de seguimiento (grupo F / U), incluido un subgrupo de hombres que tenían relaciones sexuales con hombres que participaron en un programa especializado de cribado y tratamiento de neoplasias anales (SCAN-group) a partir de 2011.PRINCIPALES MEDIDAS DE RESULTADO:Tasas de incidencia del carcinoma anal a células escamosas.RESULTADOS:De las 3878 personas que viven con el VIH incluidas en el grupo F / U, 897 fueron transferidas al grupo SCAN, 1584 (41%) eran hombres que tenían relaciones sexuales con hombres. El seguimiento total fue de 29228 personas-año con una tasa de incidencia general de carcinoma anal a células escamosas de 68,4 / 100000 personas-año [intervalo de confianza del 95%: 46,7-97,4]. El cambio en las tasas de incidencia / 100000 personas-año (intervalo de confianza del 95%) a lo largo del tiempo fue 20,7 (3,40-80,5) para 2004-2006, 37,3 (13,4-87,3) para 2007-2010 y 97,8 (63,8-144,9) para 2011-2017, p0,001. El impacto más fuerte en la incidencia del carcinoma a células escamosas anal fue la falta de restauración inmunológica [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 6,59 (4,24-10); p0,001], categoría C de los Centros de Control de Enfermedades [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 7,49 (5,69-9,85); p0,001] y no hombres que tenían relaciones sexuales con hombres [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,07 (0,05-0,10); p0,001] en el análisis de Poisson. Desde 2010-2017, las tasas de incidencia (intervalo de confianza del 95%) de carcinoma anal a células escamosas dentro del grupo SCAN y los hombres que tienen relaciones sexuales con hombres del grupo F / U fueron 95,7 (39,6-202) y 201 (101- 386) / 100000 personas-año [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,30 (0,23-0,39); p0,001]. La razón de la tasa de incidencia (intervalo de confianza del 95%), incluidos los no hombres que tenían relaciones sexuales con hombres en F / U, fue de 0,87 [0,69-1,11); p = 0,269].LIMITACIONES:No se pudo cuantificar la adherencia a las visitas.CONCLUSIÓNES:La tasa de incidencia del carcinoma anal a células escamosas en personas que viven con el VIH aumentó significativamente de 2004 a 2017, especialmente en hombres que tenían relaciones sexuales con hombres que no se someten a pruebas de detección. La participación en el programa SCAN redujo significativamente la incidencia de carcinoma anal a células escamosas en hombres que tenían relaciones sexuales con hombres, en quienes se debe prestar una especial atención, sobre todo en aquellos que se presentan en la categoría C de los Centros de Control de Enfermedades con inmunodeficiencia avanzada. Consulte Video Resumen en http://links.lww.com/DCR/B734.
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- 2021
3. Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes
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Maria R. Jimenez-Leon, Carmen Gasca-Capote, Laura Tarancon-Diez, Beatriz Dominguez-Molina, Macarena Lopez-Verdugo, Ryan Ritraj, Isabel Gallego, Ana I. Alvarez-Rios, Joana Vitalle, Sara Bachiller, María Inés Camacho-Sojo, Alberto Perez-Gomez, Nuria Espinosa, Cristina Roca-Oporto, Mohamed Rafii-El-Idrissi Benhnia, Alicia Gutierrez-Valencia, Luis F. Lopez-Cortes, and Ezequiel Ruiz-Mateos
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Articles ,General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
BACKGROUND: Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors. METHODS: pDCs, CD4 and CD8 T-cells were isolated from 450 ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed. FINDINGS: pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC. INTERPRETATION: These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies. FUNDING: This work was supported by 10.13039/100005564Gilead fellowship program, the 10.13039/501100004587Instituto de Salud Carlos III (10.13039/501100008530Fondo Europeo de Desarrollo Regional, 10.13039/501100002924FEDER, “a way to make Europe”) and the Red Temática de Investigación Cooperativa en SIDA and by the 10.13039/501100003339Spanish National Research Council (10.13039/501100003339CSIC).
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- 2023
4. TLR Agonists Enhance HIV-Specific T-Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes
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Maria Reyes Jimenez-Leon, Carmen Gasca-Capote, Laura Tarancon-Diez, Beatriz Dominguez-Molina, Macarena Lopez-Verdugo, Ryan Ritraj, Ana Isabel Alvarez-Rios, Joana Vitallé, Sara Bachiller, Alberto Pérez-Gómez, Nuria Espinosa, Cristina Roca-Oporto, Mohamed Rafii-El-Idrissi Benhnia, Alicia Gutierrez-Valencia, Luis Fernando López-Cortés, and Ezequiel Ruiz-Mateos
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Plasmacytoid dendritic cells (pDCs) sense microbial products through TLR-7 and -9 and translate this sensing in Interferon-α (IFN-α) production and T-cell polarization. The understanding of the mechanisms involved in pDCs stimulation may contribute to immunotherapeutic strategies aiming to decrease HIV-1 reservoir. Here, we characterize the immunomodulatory effects of TLR agonist stimulations through a pDC/T-cell coculture in different HIV-1 disease progression phenotypes and healthy donors (HD). pDCs were previously stimulated with AT-2-HIV-1, CpGA, CpGC and GS9620. After coculture with autologous CD4 or CD8 T-cells we observed an increase of pDCs activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels. This pDCs coordinate activation was prominent with CpGC and GS9620 and induced an increase of HIV-specific T-cell response. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with T cell polarization for eliciting antiviral response which is essential for HIV eradication strategies.
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- 2022
5. Toll-like Receptor Agonists Enhance HIV-specific T Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes
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Ezequiel Ruiz-Mateos, Maria Reyes Jimenez-Leon, Carmen Gasca-Capote, Laura Tarancon-Diez, Beatriz Dominguez-Molina, Macarena Lopez-Verdugo, Ryan Ritraj, Ana Isabel Alvarez-Rios, Joana Vitallé, Sara Bachiller, Alberto Pérez-Gómez, Nuria Espinosa, Cristina Roca-Oporto, Mohamed Rafii-El-Idrissi Benhnia, Alicia Gutierrez-Valencia, and Luis Fernando López-Cortés
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Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing in Interferon-α (IFN-α) production and T cell polarization. These cells are considered a link between innate and adaptive immunity, inducing and maintaining antigen-specific T cell responses and contributing to the control and eventually to the chronic immune activation and disease progression in HIV-1 infection scenario. The understanding of the mechanisms involved in pDCs stimulation may contribute to immunotherapeutic strategies aiming to decrease HIV-1 reservoir. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations through a pDC/T cell coculture in different HIV-1 disease progression phenotypes and healthy donors (HD). pDCs were previously stimulated with AT-2-HIV-1, CpGA, CpGC and GS9620. After coculture with autologous CD4 or CD8 T cells we observed an increase of pDCs activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels. This pDCs coordinate activation was prominent with CpG-C and GS9620 and induced an increase of HIV-specific T cell response. This pDCs dependent HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production. Interestingly, pDCs activation in people on ART was similar to that found in people that spontaneously control the virus. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with T cell polarization for eliciting antiviral response which is essential for HIV eradication strategies.
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- 2022
6. High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world
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Ana María Martínez-Sapiña, Concepción Grau, Maria Rios, Javier Crespo, Óscar Pérez, Elisa Fernández, Antonio Rivero-Juárez, Carlos Mínguez, Juan Carlos Alados-Arboledas, Miguel Jimenez, Joaquín Primo, Antonio Poyato, Juan Manuel Pascasio, Mónica Vélez, Natalia Chueca, Juan Arenas, Javier Salmerón, Berta Becerril, José Luis Montero, María Dolores Ocete, Clotilde Fernández, Marta Casado, Sergi Reus, Teresa Aldámiz-Echevarría, Carolina Freyre, Pedro Antequera, María Jesús Vivancos-Gallego, Carmen Hidalgo, Miguel Angel Simón, Cristina Delgado, Alberto de la Iglesia, Dolores Merino, Enrique Bernal, Mar Masiá, José Hernández-Quero, Daniel Navarro, Nuria Espinosa, Carlos Galera, Federico García, Ana Belén Pérez, Antonio Aguilera, Jesús Santos, Patricia Martín, Fernando Jiménez, María Jesús Téllez, José Miguel Rosales-Zábal, Silvia García-Bujalance, Juan A. Pineda, María Magdalena Lara-Pérez, Francisco Téllez, Marcial Delgado, Pilar Rincón, Francisco Javier Rodríguez, Roberto Alonso, José De Juan, Antonio García-Herola, María Dolores Espinosa, Antonio Collado, Francisco Jesús Vera-Méndez, Rosario Hernández, José Joaquin Antón, Miguel Ángel Von-Wichmann, Miguel García-Deltoro, Isabel García-Arata, Felicitas Diaz-Flores, Mohamed Omar Balghata, Instituto de Salud Carlos III, European Commission, Fundación Progreso y Salud, Junta de Andalucía, and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
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Cyclopropanes ,Male ,0301 basic medicine ,Pyrrolidines ,Sustained Virologic Response ,Sofosbuvir ,Resistance testing ,Hepacivirus ,Viral Nonstructural Proteins ,Direct-acting antivirals ,chemistry.chemical_compound ,0302 clinical medicine ,Resistance-associated substitution ,Anilides ,Prospective Studies ,Sulfonamides ,education.field_of_study ,Imidazoles ,virus diseases ,Valine ,Hepatitis C ,Middle Aged ,Retreatment ,HCV ,Cohort ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,medicine.drug ,Cohort study ,RASs ,medicine.medical_specialty ,Genotype ,Proline ,Lactams, Macrocyclic ,Voxilaprevir ,Population ,Antiviral Agents ,03 medical and health sciences ,Internal medicine ,Drug Resistance, Viral ,Ribavirin ,medicine ,Humans ,education ,Fluorenes ,Ritonavir ,Hepatology ,business.industry ,medicine.disease ,digestive system diseases ,Regimen ,030104 developmental biology ,Treatment failure ,chemistry ,Spain ,Benzimidazoles ,Carbamates ,business - Abstract
GEHEP-004 Study Group: María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Óscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau., [Background & Aims] Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available., [Methods] GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded., [Results] A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin., [Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited., [Lay summary] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations., This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040), Fundación Progreso y Salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).
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- 2019
7. Shorter Time to Discontinuation Due to Treatment Failure in People Living with HIV Switched to Dolutegravir Plus Either Rilpivirine or Lamivudine Compared with Integrase Inhibitor-Based Triple Therapy in a Large Spanish Cohort
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Ramón Teira, Helena Diaz-Cuervo, Filipa Aragão, Manuel Castaño, Alberto Romero, Bernardino Roca, Marta Montero, Maria José Galindo, Maria Jose Muñoz-Sánchez, Nuria Espinosa, Joaquim Peraire, Elisa Martínez, Belén de la Fuente, Pere Domingo, Elisabeth Deig, María Dolores Merino, Paloma Geijo, Vicente Estrada, María Antonia Sepúlveda, Josefina García, Juan Berenguer, Adriá Currán, [Teira R] Service of Internal Medicine, Hospital de Sierrallana, Torrelavega, Spain. [Diaz-Cuervo H] Gilead Sciences, MAOR, London, UK. [Aragão F] Maple Health Group, New York City, NY, USA. NOVA National School of Public Health, Public Health Research Centre, Unversidade NOVA de Lisboa, Lisboa, Portugal. [Castaño M] Hospital Regional Universitario de Málaga, Málaga, Spain. [Romero A] Hospital Universitario de Puerto Real, Puerto Real, Spain. [Roca B] Hospital General de Castellón, Castellón, Spain. [Deig E] Hospital General de Granollers, Granollers, Spain. [Currán A] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Hospital General de Granollers
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Microbiology (medical) ,virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH [ENFERMEDADES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,HIV ,Effectiveness ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Infectious Diseases ,Virologic failure ,Adverse events ,Time to discontinuation ,Medicaments - Efectes fisiològics ,Medicaments - Eficàcia ,VIH (Virus) - Tractament ,Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [DISEASES] ,Two-drug combinations ,Triple therapy - Abstract
Introduction Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). Methods All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. Results Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. Conclusion In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs. Plain Language Summary People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects.
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- 2021
8. Pérdidas de seguimiento de personas con infección por el VIH en la cohorte española VACH en el periodo 2013-2014: importancia de los factores sociodemográficos
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Fernando Lozano de León, M. José Galindo, Elisabeth Deig, Elisa Martínez, Francisco Téllez, Mar Gutierrez, Marta Montero, Ramón Teira, Pepa Muñoz-Sánchez, Nuria Espinosa, Joaquim Peraire, and Francisco Gonzalez
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0301 basic medicine ,Microbiology (medical) ,03 medical and health sciences ,0302 clinical medicine ,030106 microbiology ,030212 general & internal medicine - Abstract
Resumen Objetivo Determinar la proporcion de personas con infeccion por VIH o sida que se encontraban en seguimiento en la cohorte VACH en 2012 y que resultaron perdidas del mismo en 2013 y 2014, asi como establecer las caracteristicas sociodemograficas relacionadas con dicha perdida. Metodos Consideramos perdidos del seguimiento a los sujetos con menos de un registro de consulta por ano analizado. Construimos modelos de regresion logistica para la estimacion de las razones de ventajas (odds ratio [OR]) y sus intervalos de confianza del 95% (IC del 95%) de las variables relacionadas con la perdida de seguimiento. Resultados El porcentaje global de perdidas en seguimiento fue del 15,5% (IC del 95%: 14,9-16,1). Las variables asociadas con la perdida de seguimiento fueron no recibir tratamiento antirretroviral (TAR) (OR: 1,948; IC del 95: 1,651-2,298), ser inmigrante (OR: 1,746; IC del 95: 1,494-2,040), el consumo de farmacos por via intravenosa como mecanismo de transmision del VIH (OR: 1,498; IC del 95: 1,312-1,711), encontrarse en situacion de desempleo (OR: 1,331; IC del 95: 1,179-1,503), no tener pareja (OR: 1,948, IC del 95: 1,651-1,298), pertenecer a un estrato socioeconomico bajo (OR: 1,279; IC del 95: 1,143-1,431) y ser atendido en un hospital con menos de 1.000 pacientes en seguimiento (OR: 1,257; IC del 95%: 1,121-1,457), ademas de menor edad y menos tiempo de seguimiento en la cohorte. Conclusiones El 15,5% de los pacientes fueron perdidos del seguimiento en un periodo de 2 anos en la cohorte VACH. Ello se asocio a una serie de variables sociodemograficas y epidemiologicas, cuya identificacion puede ser util para disenar iniciativas focalizadas sobre las poblaciones mas susceptibles de abandonar los circuitos asistenciales y a orientar estrategias disenadas a la consecucion del objetivo 90-90-90.
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- 2019
9. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study
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Jaime Fernández-Bujarrabal Villoslada, Beatriz Dietl Gómez-Luengo, Daniel Ortiz-Sánchez, José Ramón Blanco Ramos, Bartolomé Gómez-Arroyo, Martín Sebastián Ruiz Grinspan, Ester Sáez de Adana Arróniz, Daniel Daniel López, Judit Villar-García, Begoña De Dios García, Josefina García García, Nuria Rabella García, Ana Rodríguez-Revillas, Lydia Martín González, Mercedes San Franco, Elena Martinez Robles, Teresa González Alegre, Elena Morcillo Rodríguez, Oriol Gasch Blasi, Laura Prieto Pérez, Isabel Jiménez Martínez, Elena Isaba Ares, Ricardo Deza-Palacios, Helena Mendez del Sol, Melchor Riera Jaume, Mercedes Rodriguez-Gutiérrez, Daniel Podzamczer, Mikel Urroz, Luis Ramos Ruperto, María Paniagua, Sergio Alcolea-Batres, Mar Masiá Canuto, Rubén Soriano-Arroyo, Paloma Merino Amador, Berta Antón-Huguet, Gabriela Alcaraz, Pablo Ryan, Carlos Franco, Leyre Díez-Porres, Juan Carlos Figueiras, Sara Lidia Kamal, Mónica Hernández, Lorena Barrera-López, Germán Ramírez-Olivencia, Kapil Laxman Nanwani Nanwani, Alberto Oreja, Montserrat Laguno, José Javier Castrodeza Sanz, Belén Loeches Yagüe, Maria Vargas, Luis Eduardo López-Cortés, Isabel Gutiérrez, Sara Vela Berna, P. Martín, Miguel Pedromingo Kus, Jesús Sanz Sanz, Mº Antonia Sepúlveda Berrocal, Carmen Yera Bergua, Juan Cuadros González, Julen Cadiñanos Loidi, Josefa Serralta Buades, María Concepción Prados Sánchez, Francesca Gioia, Iris Pedrola Gorrea, Francisco Arnaiz de las Revillas, Xabier Kortajarena Urkola, Laia Lorenzo-Esteller, Ruth Bravo-Lizcano, Angel Iniesta, Sofía González-García, Belén Martínez López, Agustín Rojas-Vieyra, Concepción García García, Raquel Cavallé-Pulla, Lucía Gómez García, Alicia Herrero, Carlos Jesús Dueñas Gutiérrez, Loreto Vidaur Tello, Carmen Fernández-Capitán, Victoria Lo-Iacono García, Cecilia Gómez-Domínguez, Adalgisa Falcone, María José Ruiz Rodríguez, Arancha Castellano, Miquel Hortos Alsina, María Concepción Nuñez, María Luisa Fernández Vidal, Jésica Abadia Otero, Natalia Moya-González, Albert Sabater Gil, Pedro de la Oliva, Ylenia María Conde-Alonso, Laura Castelo Corral, José Mº García de Lomas Guerrero, Verónica Pérez-Blanco, Isabel San Juan, Martina Archinà, Júlia Sellarés, Juan Carlos Ramos, Cintia María Martínez Mateu, Belén Fernández-Puntero, Andrea Torrecillas-Mainez, Luis Falgueras López, Carlos Carpio-Segura, María Gandullo-Moro, Francisco Abellán Martínez, Cristina Díez, Pilar Martín Dávila, Silvia Gómez-Zorrilla, María Pilar García García, Renzo Tejada-Sorados, María Dolores del Toro, E. Álvarez-Rojas, Gema Muñiz, Lucía Cajuela, María Novella Mena, Estel Pons Viñas, Andrea Pérez Rodríguez, Benito Almirante, Mónica Gozalo, Patricia Girón De Velasco-Sada, Camilo Sanz Zamudio, Ángeles García Flores, Joaquín López-Contreras González, Blanca Fabre-Estremera, Pelayo Fernández Cidón, María Martínez-Redondo, Paula Alejandra Hernández-Liebo, Juan Herrero, Marta Duque-Alcorta, María Teresa García Morales, Concepción Amador Prous, Alex Soriano, Raquel Hernando Nieto, Raquel Álvarez Franco, Alfonso Cabello Úbeda, Luis Force Sanmartín, Laura Mao Martín, Daniel Prieto-Arribas, Mario Pérez-Butragueño, Pere Domingo Pedrol, Henar Serrano-Martín, Mónica Zubimendi, M. Rodríguez-Rubio, David Pujol-Pocull, Manuel García-Gutiérrez, Carlos Manrique de Lara, Lucy Abella Vázquez, Marta Navarro Vilasaró, Carlota Cascajares-Sanz, Berta Torres, Daniel Ceniza-Pena, Isidro Moreno Gómez-Limón, María Rodríguez Mahía, Alí Martakoush, Antonio Buño-Soto, Patricia Serrano de la Fuente, Claudia González Rico, Teresa Pedraz, Conchita Pérez-Jorge Peremarch, Elena Trigo Esteban, Rosana Rouco Esteves Marques, Juan Mora Delgado, Inés Pérez Zapata, Sandra Pérez-Recio, María Ángeles Domínguez, Manuel Cervantes García, Francisco Reinoso-Lozano, M. Martí De Gracia, Carmina Oltra, Beatriz Pérez-Monte Mínguez, Guillermina Bejarano-Redondo, Sara Heili Frades, María Paz García Butenegro, Miguel Torralba González de Suso, Elena Álvaro-Alonso, Víctor J Moreno Cuerda, Gonzalo Garzón, Marcelo Daltro-Lage, Alberto Serrano Martínez, José María Aguado, Mar Mosquera, Ruth Figueroa Cerón, Juan Carlos Martin Gutiérrez, Javier Oliver Ortega, Esteban Martínez, Cristina Gómez-Ayerbe, Nerea Carrasco Antón, María Carmen Fariñas Álvarez, José Antonio Ruiz, Justo Menéndez, Lucía Díaz, José L. Casado, Pilar Vizcarra, Javier Veganzones, Miguel Ángel Moran Rodríguez, Mercedes López-Martinez, Emilio Letang, Paloma Romero Gallego-Acho, Julia Vasquez-Manau, Alexander Rombauts, Marta Robledo del Prado, Luis Puente, Beatriz Alvarez, Juan Emilio Losa García, José Tomas Algado Rabasa, Rafael Torres Perea, Angélica Rivera-Núñez, Esther Expósito Palomo, Antonio J. Carcas, Lucía Platero-Dueñas, Irene Martín Rubio, Miguel Salavert Lletí, Claudia García-Vaz, Antonio Martínez-Verdasco, Jorge Díaz-Garzón, Javier Nieto Arana, Fernando Cadenas-Gota, Richard Rojas, Abelardo García de Lorenzo, Juan Carlos López, Pedro Luis Martinez Hernández, Manuela de Pablos-Gómez, Pablo Alonso, Enrique Seco, María García-López, Lorena López-Corcuer, Celia Blasco-Andres, Delia Romera-Cano, José M. Azcona Gutiérrez, Almudena Gutiérrez-Arroyo, Paula Mendoza Roy, Ignacio De los Santos Gil, Miguel Angel Sánchez-Castellano, Sara Medrano Pardo, Mikel del Álamo Martínez de Lagos, Rocío Martínez Avilés, Elisabet Martínez-Cerón, José Manuel Vázquez Comendador, Marta Virgós-Varela, Alejandra Álvarez Brandt, Carmen Herrero Rodríguez, Jorge Martínez Jordán, Antonio Rezusta López, Marta Vizcaíno Callejón, Manuela Simon-Velasco, Jorge Ignacio Alonso-Eiras, Elisa García Vázquez, Mercè Gurguí Ferrer, Mónica González Bardanca, Nataly Cancelliere-Fernández, José Luis Díaz de Tuesta del Arco, María Larrosa, Alejandro García García, Carmen Román-Hernández, Elena Calvin-García, José Sanz Moreno, Miguel Silvestre-Niño, Nieves Valcarce Pardeiro, Maria Teresa Corcuera-Pindado, Enrique Monteoliva, Aina Gabarrell Pascuet, Elena María Aranda Rife, Aina Gomila Grange, Alba Alastrué Violeta, Daniel Roger Zapata, Jaime Montserrat, Eduardo Malmierca Corral, Marco Palma, Blanca Martínez Cifre, Gema Domínguez de Pablos, Emilio Cuesta, Eva Perales, Silvia Hernáez Crespo, Juan Torres-Macho, Adrián Sánchez Montalvá, Rocío Montejano Sánchez, Eva Van den Eynde Otero, Silvia Castañeda Espinosa, Virginia Pérez Doñate, Adriana Hernández Belmonte, Laura Iglesias Llorente, María Sanz de Pedro, Juan Espinosa Pereiro, Lubna Dani Ben-Abdellah, Raquel Barrós González, Iván Piñero, Araceli López-Tofiño, Ana Such-Diaz, Karim Mohamed Ramírez, Pilar Toledano Sierra, Rebeca Izquierdo, Guillermo Cuevas, Andrés Felipe Cardona Arias, Ileana Gabriela-Tomoiu, David Vinuesa García, Ander González Sarria, Stephan Stuart, José María Fernández, Javier Torres-Cortés, Elisabet Delgado Sánchez, María Varela-Cerdeira, Gemma Bassani, Berta Román Bernal, Isabel García, Paula Betancort de la Torre, Yolanda Martínez-Abad, Beatriz Arizcun, Juan José Cabanillas-Martín, Guillermo Estrada Fernández, Oscar del Río Pérez, Inmaculada Martín Pérez, Andony García, Luis Gómez-Carrera, Alexander Agrifoglio, Alberto M. Borobia, Jordi Niubó, Vanessa Alende Castro, Lara Montes Andújar, Alexandra De la Vega, Efrén Sánchez Vidal, Isabel A. Pérez Hernández, Laura Frade-Pardo, Ana Josefa Tebar-Martinez, Silvia Álvarez Kaelis, Sara De la Fuente Moral, Luz Martin Carbonero, Juan Cantón De Seoane, María Dolores Montero-Vega, Juan Carlos Gainzarain Arana, Sergio España Cueto, Rocío Nuñez-Cabetas, María Sánchez-Martín, Constanza Muñoz Hornero, Ana Gómez-Zamora, Javier Díaz Luperena, Patricia González-Donapetry, José Miguel Cisneros, Lucía Hernández-Rivas, Patricia González Ruano, Andrea Espigares Correa, Rocío González-León, Nicolás García-Arenzana, Omar Cervera, Andrés Canut Blasco, Ana Isabel Cañabate, Mercedes Villarreal García-Lomas, Melania Íñigo Pestaña, Maria Álvarez de Castro, Ana Correa Ruiz, Belén Civantos, Lydia Pascual-García, Paula Villares Fernández, Mikel Rico-Briñas, María José Alcaide-Martín, Adoración Valiente, Victoria Arnalich-Montiel, Pilar Retamar, Jesús Mingorance, Eva María Romay Lema, Pablo Galindo-Ballesteros, M. Teresa Pérez-Rodríguez, Rosario Maria Torres Santos-Olmo, Inmaculada Pinilla, Elie Dahdouh, Beatriz Tejero-Soriano, Cristina Pizarro-Sanchez, Félix Gutiérrez Rodero, Luis Jara-Palomares, María Hernández-Gancedo, Cristina Chico Chumillas, Sergio Gilaberte Reyzábal, Manuel González-Viñolis, Ana Martínez Sapiña, Francisco Parras, Teresa Rubio Obanos, Iker Falces-Romero, Adriana Sánchez Serrano, Teresa Álvarez de Espejo Montiel, Jorge Valencia, Miquel Pujol, José Luis Velasco Garrido, Belén Calderón-Llopis, Álvaro Varela Plaza, Abel Caro, Juan José González-Garcia, Miguel Sampedro Núñez, María Fernández-Velilla, Emilio Cendejas-Bueno, María Cecilia Cánepa, José Luis Santiago Blanco, Alicia Rico-Nieto, Mónica Liébana Gómez, Sarah Caro Bragado, Susana Sánchez-Rico, José María Marimón Ortiz de Zárate, Paloma Dorao, Cristina Plaza-Moreno, Isabel Valbuena, Natividad Benito Hernández, Ginger Giorgiana Cabrera Tejada, Jordi Carratalà, Sara Fernández Rodríguez, Vicente Ferrer Díaz De Brito Fernández, Pilar Catalán, Pablo Mariscal-Aguilar, Germán Daroca-Bengoa, Rafael Fernandez, Raquel Casitas-Mateo, Ester Zamarrón de Lucas, Úrsula Quesada, Julio Yagüe, María Isabel Quijano Contreras, Trinidad Baselga-Puente, Lourdes Herrera Pacheco, Carlota Gudiol, Alazne Lartategi Iraurgi, Estefanía Martinez-Chavez, Silvia Valero Rovira, Alba Bergas, Zaida Ruiz de Azua, Teresa Prim, Cristina García-Quero, Pilar Hernández Machín, Rubén Gomez-Rioja, María Pavón-Masa, María de las Mercedes Valentín-Pastrana Aguilar, Ilduara Pintos Pascual, Lucía Brieba-Plata, María Jesús Domínguez Santalla, Francisco Javier Membrillo de Novales, Raúl Galera-Martínez, Ana Lérida Urteaga, Miguel Cervero, Alberto Mangas-Moro, José Hernández Quero, Teresa Sancho Bueso, María Angustias Quesada Simón, Luz Parra-Gordo, Sofía Díaz-Carrasco, Juan Carlos Abad Almendro, Andrés Javier Ruiz Fernández, Estíbaliz Molina Iturritza, Aurea Díez-Tascón, Yale Tung-Chen, Marta Rava, Carlos Villasante, Gabriel Gaspar Alonso-Vega, Clara Cabré-Verdiell Surribas, Esther Fraile Villarejo, Aida Gutiérrez García, Ana Robustillo-Rodela, Rafael Padrós Selma, Jesús Rodríguez-Baño, Frank Perdomo-García, Lydia de la Fuente Regaño, María del Mar Arenas-Miras, Cristina Rodríguez Roca, Blanca Montero-San Martín, Gema Crespo-Sánchez, Miguel Ramírez-Verdyguer, Alberto Diaz de Santiago, Marta Díaz Menéndez, María de la Luz Padilla Salazar, Silvia Arribas-Terradillos, Sadaf Zafar Iqubal-Mirza, Isabel Rábago Lorite, Belén Estébanez, Maite Ganchegui Aguirre, André Barbosa Ventura, Estefanía Fernandez-Cerezo, Maria Eulalia Valencia, Zaira R. Palacios-Baena, Beatriz Diaz Pollan, Lidia Martín, Sara Fabra-Cadenas, José Miguel Cantero-Escribano, Carmen Busca Arenzana, Emilia Guasch-Arévalo, Virginia Fernández Espinilla, Ainhoa Urrutia Losada, Oscar Noya González, Raquel Aranega, Alejandro Rodríguez Saenz de Urturi, María Jesús Jaras Hernandez, Charbel Maroun Eid, Marta Mora Rillo, Antonio Ramos Martínez, Meritxell Ortega Montoliu, Jose María Mostaza, Sonia García Calvo, Cristina Verdú, Celia Salamanca, Cristina Cervera Acedo, Mónica Martínez, Miren Urrestarazu Larrañag, Carmen Barroso Castro, Ivo Vives-Beltrán, Lorea Arteche Eguizabal, Ana Montero, Javier Balsa Vázquez, Amparo Perez-Garcia Morillón, Alejandra Pérez García, Isabel Pérez-Tamayo, Rafael Cantón Moreno, Antonio Marín-García, Inmaculada Jarrín, Núria Trullen, Ines Fernandez-Jimenez, Guillermo Ruiz-Carrascosa, Almudena Villa Martí, Jamil Cedeño, Marcos Díez Martínez, Carlos Lahoz, Lorena De la Mora, Javier Sánchez-Lora, Ana María Martínez-Virto, Irene Sanjosé Muñiz, Adrian Peña-Hidalgo, Cristina López Mestanza, Carola Gutiérrez, Ana Laila Qasem-Moreno, Irene Salvo García, Lucía Fernández de Orueta, Jorge Parra Ruiz, Sergio Pérez Pinto, Carlos García-Mochales Fortún, Esteban García de las Heras, Patricia González Muñiz, Mario Fernández-Ruiz, Anna Ferrer Santolaria, Olga Sánchez Pernaute, Julieta Latorre, Jesús Manzanares, Miguel Angel Martinez Gallego, Helena Notario, Ángel Rodríguez-Villodres, Eva Fernández-Bretón, Encarnación Moral Escudero, Mónica Sánchez-Santiuste, Carmen Martínez Cilleros, Ricardo Fernández Roblas, María Yllescas, Eva Soria-Alcaide, Marta Arsuaga Vicente, Marta Gómez-López, Regina Cabrera-Gamero, Natalia Carrasco Fons, Diana Piñar Cabezos, Begoña Sánchez-Sánchez, Francisca Garcia-Iglesias, Raquel Marín-Baselga, Alberto Arranz Caso, Virginia Guedez-López, Lucia Boix Palop, Íñigo Gredilla Zubiría, María Hidalgo-Sánchez, Laura López-Tappero Irazábal, José Ignacio Bernardino de la Serna, Javier Queiruga, Natalia Guadalupe Barrera-López, María López-Jodar, Jorge Calderón Parra, Diego Rodríguez-Álvarez, José Molina, María Luisa Montes, Beatriz Rodríguez-Alonso, Daniel Useros Brañas, Maria Gracia Liras-Hernández, Lucía Romero-Imaz, Nieves Jaén Sánchez, Marta Segovia-Amaro, Marta Vara, Maribel Zamora Cintas, Montaña Jiménez Álvaro, Alberto Moreno Fernandez, Asunción Díaz, Jordi Mancebo Cortés, Francisco Javier De Castro Vega, Álvaro Navarro Batet, Francisco Javier Sagra, Alexandre Pérez González, Luis Castro, Isabel Barrio López, Marta Ruiz-Alguero, Silvia Ossaba-Vélez, Alberto Martín-Vega, Maria Jesus Bustinduy Odriozola, Sivia Pastor-Yvorra, Nuria Espinosa, Elena Múñez Rubio, María E García-Leoni, Sandra Rosillo, Cristina Carbonell, Iván Navas Clemente, Paula Arriola Martínez, Marta Peña, Lucía Martínez de Soto, Roberto Mora-Corcovado, Alberto Iglesias-Sigüenza, Rocío Ruíz-Hueso, Elena Alvar, Pedro Camacho, Jesús Sojo-Dorado, Remedios Alemán Valls, Ines Ponz, Esmeralda Palmier Peláez, María Arcos Rueda, Guillermo Maestro de la Calle, Ramón Pérez Tanoira, Ana Martínez Vidal, Cristina Amodeo, Marina Pacheco Martínez-Atienza, Clara Muñoz Aguirre, Felipe Villar Álvarez, Giorgina Salgueiro, Xavier Sanz Salvador, César Pérez-Romero, Beatriz Álvarez Zapatero, Nelsa González-Aguado, Robert Torres Sánchez del Arco, Enrique Míguez Rey, Merce Sirisi, Xavier Bonfill Cosp, Marta Yagüe-Barrado, Elena Pérez-Costa, Sandra Casares, Eva Estirado, Jorge Alvarez Troncoso, Cristina Martín-Carrasco, Diana Sande Llovo, Melchor Álvarez de Mon Soto, Arantzazu Mera Fidalgo, Francisco Marqués-González, Agustín Valido-Morales, Luis Alberto Nieto Fernández del Campo, Helem Haydee Vilchez, María Rivas-Carmenado, Francisco Moreno, Ignacio Fernández-Fernández, Henar Calvo Sánchez, Ana González-Cordón, Isabel Fernández-Navarro, María Simón Sacristán, Eva Jiménez-González de Buitrago, M. Muñoz, María Laplaza-González, Rosa de Miguel Buckley, Marta Redondo-Gutierrez, Paula Santibáñez Sáenz, Raquel Martínez Goñi, Marta Rico Rodríguez, Carlos Toro-Rueda, Francisco Arnalich, Ana Santiago-Recuerda, Clara Soto Abanedes, María Dolores Herrero Mendoza, Aquilino Sanchez Purificación, Diego Franch Llasat, María Velasco Arribas, Alejandro Martín-Quirós, Jorge Alba Fernández, Elena Ramírez, Amparo López-Bernus, Marta Alvarado, María Rexach Fumaña, Martín Pilares-Barco, Carmen Liébana Martos, Yolanda Martínez Martínez, Nicolas Merchante Gutiérrez, Maria José Asensio, Ianire Virto Peña, Lucía Mejuto-Illade, María Angeles Martinez-López, Pilar López-Pirez, Alejandro Suárez, Cristóbal Manuel Rodríguez Leal, Sara Garcia-Bellido Ruiz, Jorge Guisández Martín, Lucia Cachafeiro, Pedro Gil Divasson, Almudena Quintás-Viqueira, Laura Currás-Sánchez, Alverio Seiz-Martinez, Mario Ruiz-Bastián, Juan José Menéndez, Jorge Orihuela Martín, María Dolores Nieto Martín, Cristina Arévalo, Rebeca Marinas, Susana Casas Rodríguez, Zuriñe Ortiz de Zárate Ibarra, Yolanda Posada Franco, Joan Gómez-Junyent, Ana María Garijo Saiz, Marina Alguacil-Guillén, Ana Alguacil, Esther Aznar Muñoz, Sara Bañón Escandell, Juan Salillas Hernando, Chiara Fanciulli, Rosa Gómez-Gil, Francisco García-Río, Moncef Belhassen-García, Belén Gutierrez Sancerni, Sonia Vega Molpeceres, Inés Suárez-García, Leire Pérez-Latorre, Elena Chamarro Martí, Carmen Rosario Herrero Gil, Belén Gutiérrez-Gutiérrez, Tatiana Mata Forte, Francesca Sánchez Martínez, Lucía Ramos Merino, Santiago Yus, Mº Ángeles Marcos, Susana Martínez-Álvarez, Alexy Inciarte, Manuel Quintana-Díaz, Lucía Serrá, Belén Alejos, Guillem Policarpo Torres, José Román Muñoz del Rey, Irene Blanco-Bartolomé, Alberto Bahamonde Carrasco, Victoria Hernando, Jhon Rojas, David Roa, María Ángeles Garcinuño, Aránzazu Villasante de la Puente, Patricia Pérez-Palacios, Jesús Ruiz Aragón, Valvanera Ibarra Cucalón, Lucía Ortega Enciso, Ismail Zakariya-Yousef Breval, Jorge Navarro López, Gema Barbeito Castiñeiras, Clara Sala Jofre, Nora Molina Torres, Manuel Poyato, Inmaculada Poquet Catala, Virginia Pomar Solchaga, María Pilar Romero-Gómez, Clara Hernández, Helena Mozas Moriñigo, Mercedes Guillamón Sánchez, Zineb Karroud, Arianna Catino, Violeta Ramos Sesma, Santos del Campo, Pilar Fernández-Calle, Ana Fernández Cruz, Fernando Salvador, Rosa Mayayo-Alvira, Pilar Barco Núñez, Ana Isabel Peláez Ballesta, Silvia Suárez Diaz, Beatriz María Sanjuan, Nora Izko Gartzia, Teresa Aldámiz-Echevarría, Cecilia Tortajada Alamilla, Pau Bosch-Nicolau, María del Mar Alonso Socas, Sonia Calzado Isbert, Jose R. Arribas, Juan Fernández-Lahera, Elizabet Petkova Saiz, Eva Jiménez, Gabriela Abelenda-Alonso, Alba Ribera Puig, Pascual Sanabria-Carretero, Sara Rodrigo González, Irene Díaz de la Torre, Tamara Manso Gómez, Carmen Sáez Barberá, Roi Suárez Gil, Paloma García-Clemente, Héctor Meijide Míguez, Elsa Izquierdo-García, Josune Goikoetxea Agirre, Olalla Martínez Macia, Jesús Santos González, Guillermo Jiménez Álvarez, Cristina Marcelo-Calvo, Javier Coy Coy, Isabel Arenas-Berenguer, Julio García Rodríguez, Natalia Yustas-Benitez, Sarai Quirós-Fernández, Marina Noguerol-Gutiérrez, María Adalid Moll, Iván Bloise-Sánchez, Mario José Rodriguez Dominguez, Elena Salamanca, Francisco Mora Gómez, Lucio García-Fraile, Pablo Millán, C Gutiérrez, Montserrat Rodríguez, José Antonio Oteo Revuelta, Joseba Portu Zapirain, Cristina Moreno, Irene Carrillo Acosta, Jorge Calvo, Ana Mariño Callejo, David Romero-Ribate, Blanca Alonso, Elena Muñoz del Val, Elena Resino Foz, Olaia Rodriguez-Fraga, Miguel Villamarín, Irene Amores-Hernández, Laura Muñoz López, Esther García Almodóvar, Ismael Casares Guerrero, Angélica Villanueva-Freije, Nuria Parra Arribas, Montserrat Sanmarti Vilamala, Macarena Lerín-Baratas, Mercedes Castro-Martínez, Melissa Carreres Candela, Lucia Suárez Pérez, Jose Manuel Iturzaeta-Sánchez, Thamires Silva-Freire, José Antonio Peregrina, María Luisa Machado Sicilia, Sergio Zurita, Daniel Molina Morant, Olga González-Peña, Fernando Lázaro-Perona, Paloma Oliver-Saez, Beatriz Mestre-Gómez, Luis Díaz Díez Picazo, Silvia García-Bujalance, Francisco Rodríguez Gómez, Pere Comas Casanova, Carlos Ruiz Martínez, Alberto Delgado-Iribarren, Berta Alonso-González, Isabel Moreno-Parra, Teresa Gómez-Ballesteros, Araceli Menéndez, Jose Manuel Añón, Ruth Jorge García, Jonathan Cámara Fernández, Miguel Górgolas Hernández-Mora, Itziar Diego Yagüe, Miriam Latorre-Millán, Covadonga Morcate Fernández, M. Río-García, Elisabet Lerma-Chippirraz, Carmen Yllera Gutiérrez, Francesc Albertí, Eva Flores, Carmen R. Uña Orejón, Patricio González-Pizarro, Neila Rodriguez-Roca, Miguel Fernández-Huerta, Inés Ferrer Ortiz, María José Blanco Vidal, Juan Pablo Avilés, Alicia Lorenzo Hernández, Mireia Puig Campmany, José Bravo-Ferrer, Gonzalo Martínez-Alés, Pablo Marguenda Contreras, M. Sánchez, Antonio García Pardo, Yolanda Meije, Francisco Tejerina, Carolina Hernández Carballo, Victoria Moreno, Daniel Laorden-Escudero, Ana Barrios Blandino, Alexia Costanza Espiño Álvarez, Ana Milagro Beamonte, Jerónimo Pachón, S San José-Villar, Marta Morando, María del Carmen Navarro Sáez, Rodolfo Álvarez-Sala Walther, Jon Ugalde Espiñeira, Fernando De la Calle Prieto, Nuria Fernández, Iván Pelegrín Senent, Alba Rueda López, Cristina Schüffelmann, Marcelino Hayek Peraza, Laura Labajo-Montero, Angel Robles Marhuenda, Pilar Durán, Ana Esteban-Romero, María Rosa Oltra Sempere, Ana Cosmen Sánchez, Alex Smithson Amat, Margarita Ramírez-Schacke, Marco Antonio Sempere Alcocer, Paloma Carrera-Vázquez, M Miarons, Teresa García Delange, Amelia Rodriguez-Mariblanca, Eva Talavera García, Roberto Vates Gómez, Óscar Sanz Peláez, José María Muñoz-Ramón, José Luis García Fogeda, Isabel Arroyo-Rico, Verónica Cano Llorente, Fernando González-Romo, Alberto Alonso-Babarro, Fátima Brañas, Fabricio Iannuccelli, Pilar Álvarez Padín, Luis Metola Sacristán, Vicente Boix, Víctor Hontañón, Juan Berenguer, José Luís Del Pozo León, Patricia Sorní Moreno, Maria Isabel Torres, Rafael Mican Rivera, Amparo Blasco Claramunt, Carmen Ardanuy, Aychel Elena Roura Piloto, María Ángeles Molina, Isabel Asschert Agüero, Julía Alvárez del Vayo, Consuelo García-Sánchez, Begoña Reche-Martínez, Guillermo Cuervo, Carlos Iniesta, María Antonia Gómez-Mendieta, Ana María Noblejas Mozo, Andres Bartrina-Tarrio, Carmen De la Higuera Arranz, Yeray Untoria Tabares, Andrés Enrique Suárez-Plaza, Jesús Frías, Paloma López-Arévalo, Irene María Llorente-Cortijo, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), and Fundación SEIMC-GESIDA
- Subjects
Male ,Prognostic variable ,medicine.medical_specialty ,Databases, Factual ,Coronavirus disease 2019 (COVID-19) ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Models, Statistical ,SARS-CoV-2 ,business.industry ,Mortality rate ,COVID-19 ,Retrospective cohort study ,Articles ,Middle Aged ,Prognosis ,medicine.disease ,Phenotype ,Hospitals ,Hospitalization ,Logistic Models ,Infectious Diseases ,Spain ,Cohort ,Female ,Lymphocytopenia ,business ,Cohort study - Abstract
REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.
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- 2021
10. Modulation of Monocyte Activation and Function during Direct Antiviral Agent Treatment in Patients Coinfected with HIV and Hepatitis C Virus
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Yusnelkis Milanés-Guisado, Maria Trujillo-Rodriguez, Ana I. Alvarez-Rios, Luis F. López-Cortés, Alicia Gutierrez-Valencia, M. Reyes Jimenez-Leon, Ezequiel Ruiz-Mateos, Pompeyo Viciana, Nuria Espinosa, Cristina Roca-Oporto, Rebeca S. de Pablo-Bernal, Ana Serna-Gallego, Laura Tarancon-Diez, Instituto de Salud Carlos III, Red Española de Investigación en SIDA, European Commission, and Junta de Andalucía
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Lipopolysaccharide ,cell-associated DNA ,Cell-associated DNA: Inflammation ,HIV Infections ,Hepacivirus ,CD49d ,medicine.disease_cause ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,CX3CR1 ,Pharmacology (medical) ,0303 health sciences ,biology ,medicine.diagnostic_test ,Coinfection ,virus diseases ,Hepatitis C ,Infectious Diseases ,medicine.anatomical_structure ,polyfunctionality ,monocyte ,HCV ,030211 gastroenterology & hepatology ,Tumor necrosis factor alpha ,Hepatitis C virus ,Activation ,Antiviral Agents ,Flow cytometry ,03 medical and health sciences ,medicine ,Humans ,030304 developmental biology ,Reservoir ,Pharmacology ,CD40 ,business.industry ,Monocyte ,HIV ,DAAs ,Hepatitis C, Chronic ,Monocyte: Polyfunctionality ,chemistry ,inflammation ,Polyfunctionality [Monocyte] ,Immunology ,biology.protein ,Inflammation [Cell-associated DNA] ,business - Abstract
The activation phenotypes and functional changes in monocyte subsets during hepatitis C virus (HCV) elimination in HIV/HCV-coinfected patients were evaluated. Twenty-two HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antiviral (DAA) therapy and 10 HIV-monoinfected patients were included. The activation phenotype (10 markers) and polyfunctionality (intracellular interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-10 production) in three monocyte subsets (classical, intermediate, and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV DNA levels were assayed by droplet digital PCR. After HCV clearance, there was a significant increase in classical monocyte and decreases in intermediate and nonclassical monocyte levels. The levels of the activation markers CD49d, CD40, and CX3CR1 were decreased after treatment in the monocyte subsets, reaching the levels in HIV-monoinfected patients. After lipopolysaccharide (LPS) stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations, such as the IL-1α− (IL-1α-negative) IL-1β− IL-6+ (IL-6-producing) IL-8− TNF-α− IL-10− combination, were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV DNA levels correlated with activation markers before but not after treatment. HCV clearance after DAA treatment in patients on cART exerts an anti-inflammatory profile on monocyte subsets, activation phenotypes, and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients., This work was supported by the Instituto de Salud Carlos III (research contracts CPII014/00025 to E.R.-M., CP19/00159 to A.G.-V., FI17/00186 to M.R.J.-L., and FI14/00431 to L.T.-D. and research projects PI16/00684 and PI19/01127 to E.R.-M.) and the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020 and RD16/0025/0019), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016, Instituto de Salud Carlos III, Fondos FEDER. E.R.-M. was supported by the Consejería de Salud y Bienestar Social of the Junta de Andalucía through the Nicolás Monardes program (C-0032/17).
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- 2020
11. Effectiveness and safety of first-line antiretroviral regimens in clinical practice: a multicentre cohort study
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Montserrat Sanmartí Vilamala, Nuria Espinosa, Carlos Iniesta, Inés Suárez-García, Alfonso Cabello-Ubeda, OSKAR AYERDI, INMA JARRIN, Esther Rodríguez-Gallego, Adrian Curran, Roberto Muga, Livia Giner, EVA POVEDA, DAVID DALMAU, Anaïs Corma-Gómez, Montserrat Vargas Laguna, Antonio Rivero Román, Juan González-García, Iñigo Sagastagoitia, Mar Vera, Marta Rava, ALICIA GONZALEZ-BAEZA, Eduardo Malmierca Corral, Maria Jose Amengual, Jose Maria García de Lomas Guerrero, MARIA REMEDIOS ALEMAN VALLS, Rocio Montejano Sanchez, Javier Martínez-Sanz, Chiara Fanciulli, Alejandro Gonzalez-Serna, Esperanza Merino de Lucas, Anna Rull, PATRICIA GONZALEZ-RUANO, Cristina Moreno Prieto, Alfonso Del Arco Jiménez, Luis Fernando Lopez.Cortes, Alexandre Pérez González, Rafael Mican, Félix Gutiérrez, Mª José Alcaraz, David Rial Crestelo, Eulalia Valle-Garay, Marta Fernández-González, Azucena Bautista Hernández, Víctor Hontañón Antoñana, and JOSE ALBERTO GARCIA GOMEZ
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Microbiology (medical) ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,HIV Infections ,Gastroenterology ,Tenofovir alafenamide ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Viral suppression ,Adverse effect ,Pharmacology ,Creatinine ,Acquired Immunodeficiency Syndrome ,business.industry ,Viral Load ,CD4 Lymphocyte Count ,Regimen ,Infectious Diseases ,chemistry ,Anti-Retroviral Agents ,Cohort ,business ,Viral load ,Cohort study - Abstract
ObjectivesWe compared 48 week effectiveness and safety of first-line antiretroviral regimens.MethodsWe analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load 0.4 and >1); (iv) CD4 percentage normalization (>29%); (v) multiple T-cell marker recovery (MTMR: CD4 > 500 cells/mm3 plus CD4 percentage >29% plus CD4/CD8 > 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE).ResultsAmong 3945 individuals analysed, the most frequently prescribed regimens were ABC/3TC/DTG (34.0%), TAF/FTC/EVG/CBT (17.2%), TDF/FTC + DTG (11.9%), TDF/FTC/EVG/CBT (11.7%), TDF/FTC/RPV (11.5%), TDF/FTC + bDRV (8.3%) and TDF/FTC + RAL (5.3%). At 48 weeks, 89.7% of individuals achieved VS with no significant differences by initial regimen. CD4 mean increase was 257.8 (249.3; 266.2) cells/mm3, and it was lower with TAF/FTC/EVG/CBT and TDF/FTC/RPV compared with ABC/3TC/DTG. CD4 percentage normalization was less likely with TAF/FTC/EVG/CBT, and MTMR was less likely with TAF/FTC/EVG/CBT and TDF/FTC + RAL. The proportion of discontinuations due to AE was higher with TDF/FTC + bDRV (9.7%), followed by TDF/FTC/EVG/CBT (9.5%) and TDF/FTC + DTG (7.9%). Compared with ABC/3TC/DTG, cholesterol and LDL mean increases were higher with TAF/FTC/EVG/CBT and lower with TDF/FTC + DTG, TDF/FTC/RPV and TDF/FTC + RAL. Higher mean increases in triglycerides were significantly associated with TAF/FTC/EVG/CBT. Regimens containing DTG showed higher creatinine increases.ConclusionsThe significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.
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- 2020
12. Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study
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Montserrat Sanmartí Vilamala, Nuria Espinosa, Carlos Iniesta, Inés Suárez-García, Federico Pulido, Alfonso Cabello-Ubeda, OSKAR AYERDI, Víctor Asensi Álvarez, INMA JARRIN, Andrés Navarro Ruiz, Ignacio De Los Santos Gil, Esther Rodríguez-Gallego, Pedro Herranz, Paloma Gijon, Mar Masiá, Adrian Curran, Roberto Muga, Mariona Xercavins, Livia Giner, LUZ MARTÍN CARBONERO, EVA POVEDA, DAVID DALMAU, Anaïs Corma-Gómez, Montserrat Vargas Laguna, Eulalia Valencia, Juan González-García, Mar Vera, ALICIA GONZALEZ-BAEZA, Eduardo Malmierca Corral, Maria Jose Amengual, Francisco Arnalich Fernandez, Jose Maria García de Lomas Guerrero, MARIA REMEDIOS ALEMAN VALLS, Rocio Montejano Sanchez, Javier Martínez-Sanz, Maria José Mellado Peña, Laura Perez-Martinez, Xavier Barber, Chiara Fanciulli, Sergio Serrano-Villar, Alejandro Gonzalez-Serna, Sergio Padilla, Esperanza Merino de Lucas, Anna Rull, PATRICIA GONZALEZ-RUANO, Cristina Moreno Prieto, Alfonso Del Arco Jiménez, Luis Fernando Lopez.Cortes, Alexandre Pérez González, Rafael Mican, Rafael Rubio García, Félix Gutiérrez, Marta Ruiz-Algueró, Mª José Alcaraz, David Rial Crestelo, Eulalia Valle-Garay, Marta Fernández-González, Asuncion Hernando, Víctor Hontañón Antoñana, Jose Arribas, JOSE ALBERTO GARCIA GOMEZ, Instituto de Salud Carlos III - ISCIII, European Regional Development Fund (ERDF/FEDER), UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Instituto de Salud Carlos III, European Commission, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), and European Regional Development Fund
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0301 basic medicine ,Male ,Enfermedad transmisible ,HIV Infections ,Quinolones ,Gastroenterology ,Estudio de caso ,0302 clinical medicine ,Medicine ,Emtricitabine ,Pharmacology (medical) ,030212 general & internal medicine ,Darunavir ,Elvitegravir ,Cobicistat ,Serodiagnóstico del SIDA ,Middle Aged ,Viral Load ,Treatment Outcome ,Tolerability ,Molecular Medicine ,Cohort studies ,Drug Therapy, Combination ,Female ,Viral load ,medicine.drug ,lcsh:Immunologic diseases. Allergy ,Adult ,medicine.medical_specialty ,Medicina ,Anti-HIV Agents ,Sida ,030106 microbiology ,Tenofovir alafenamide ,03 medical and health sciences ,Highly active antiretroviral therapy ,Virology ,Internal medicine ,Humans ,Tenofovir ,business.industry ,Research ,HIV infection ,Regimen ,Spain ,HIV-1 ,business ,lcsh:RC581-607 - Abstract
© 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)”.
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- 2020
13. Is immune recovery different depending on the use of integrase strand transfer inhibitor-, non-nucleoside reverse transcriptase- or boosted protease inhibitor-based regimens in antiretroviral-naive HIV-infected patients?
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Yusnelkis Milanés-Guisado, Alicia Gutierrez-Valencia, Luis F. López-Cortés, Antonio Rivero, Ezequiel Ruiz-Mateos, Maria Trujillo-Rodriguez, Nuria Espinosa, Cristina Roca-Oporto, Pompeyo Viciana, Juan Manuel Muñoz-Pichardo, Red Española de Investigación en SIDA, Instituto de Salud Carlos III, and European Commission
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Adult ,Male ,Microbiology (medical) ,CD4-CD8 Ratio ,Integrase inhibitor ,Non-nucleoside reverse transcriptase inhibitors ,Brief pain inventory ,Anti-retroviral agents ,Pharmacology ,Integrase ,hiv infections ,Nucleoside Reverse Transcriptase Inhibitor ,Transfer technique ,Endopeptidases ,Integrase inhibitors ,Humans ,Medicine ,Pharmacology (medical) ,Protease inhibitor (pharmacology) ,HIV Integrase Inhibitors ,t-lymphocytes ,Retrospective Studies ,cd4 count determination procedure ,Viral load result ,biology ,business.industry ,Repeated measures design ,Nucleosides ,HIV Protease Inhibitors ,Middle Aged ,Viral Load ,Immune reconstitution ,Reverse transcriptase ,humanities ,Peptide hydrolases ,CD4 Lymphocyte Count ,Infectious Diseases ,Blood hiv rna ,biology.protein ,Reverse Transcriptase Inhibitors ,Female ,Ncleoside reverse transcriptase inhibitors ,business ,Viral load ,CD8 - Abstract
[Objectives] To analyse whether integrase inhibitor (InSTI)-based regimens achieve better immunological recovery than NNRTI- or boosted PI (bPI)-based regimens as initial ART., [Methods] In a retrospective analysis, we selected patients who initiated ART with two NRTIs plus an InSTI, an NNRTI or a bPI and maintained both the same ‘third drug’ and an HIV-RNA, [Results] Of the 836 patients included, 208, 481 and 147 initiated with InSTI, NNRTI and bPI, respectively. For CD4+, %CD4+ and CD4+/CD8+ two main slopes were identified: from month 0 to month 6, with the highest increments; and from month 6 to month 24, with smaller increases every semester. Although the patients on InSTI achieved undetectable viral load faster, for CD4+ and %CD4+ there were no differences in the slopes of change according to the third drug either for the first phase (P=0.137 and P=0.393, respectively) or from month 6 onwards (P=0.834 and P=0.159, respectively). The increase in CD4+/CD8+ was slightly higher for bPI compared with InSTI (difference of 0.0119, 95% CI 0.0020–0.0205; P=0.018), but clinically negligible. From month 6 onwards, no differences were found between treatment groups (P=0.176)., [Conclusions] Immune restoration measured as CD4+ count, %CD4+ and CD4+/CD8+ increases was independent of the third antiretroviral drug class used when given with two NRTIs., This work was supported by Red de Investigación en SIDA (RD16/0025/0020-ISCIII-FEDER) and Instituto de Salud Carlos III and Proyectos de investigación en salud (AES 2018) (exp. PI18/01298).
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- 2020
14. Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients
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José Luis Santiago Blanco, José L. Casado, Rocío Montejano, Nuria Espinosa, Jorge Vergas, Rosario Palacios, Marta Montero, Pilar Vizcarra, María José Galindo, Miguel García Deltoro, Alberto Diaz de Santiago, Juan Carlos López, Álvaro Mena, Eugenia Negredo, and Alfonso Cabello
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Male ,Resistance ,Human immunodeficiency virus (HIV) ,HIV Infections ,darunavir ,Comorbidity ,Hepacivirus ,030312 virology ,medicine.disease_cause ,Simplification ,0302 clinical medicine ,Hiv infected patients ,Pharmacology (medical) ,030212 general & internal medicine ,Darunavir ,Aged, 80 and over ,0303 health sciences ,Coinfection ,switching ,Middle Aged ,Viral Load ,Hepatitis C ,Treatment Outcome ,Infectious Diseases ,Female ,raltegravir ,medicine.drug ,Adult ,medicine.medical_specialty ,Dual therapy ,Anti-HIV Agents ,Dermatology ,Treatment experienced ,resistance ,03 medical and health sciences ,Raltegravir Potassium ,Internal medicine ,medicine ,Humans ,HIV Integrase Inhibitors ,Aged ,Retrospective Studies ,Toxicity ,business.industry ,Public Health, Environmental and Occupational Health ,simplification ,toxicity ,HIV Protease Inhibitors ,Raltegravir ,Spain ,Switching ,business - Abstract
BIRDi study group., The use of two potent, well-tolerated, drugs could permit the maintenance of virologic suppression even in heavily pretreated people living with HIV. In this retrospective, multicenter, simplification study (NCT03348449), we included those patients with virologic suppression who switched to raltegravir (RAL) plus boosted darunavir (b/DRV). Overall, 345 patients (75 females, 25%) were included. Patients were largely pretreated (mean, 9.4 regimens), suppressed for a median of 41.1 months. Fifty patients had ≥1 mutation against DRV. At 96 weeks, the efficacy by intention-to-treat analysis (snapshot) was 73% (95%CI, 68.4–77.8%), but 97.1% (95%CI, 95.4–98.9) excluding changes due to non-virologic reasons, and virologic failure was rare (0.9%; 95%CI, 0.1–1.2%). Median CD4/CD8 ratio increased from 0.59 to 0.62 (p
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- 2020
15. Lack of impact of protease inhibitor resistance-associated mutations on the outcome of HIV-1-infected patients switching to darunavir-based dual therapy
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Rocío Montejano, Nuria Espinosa, José L. Blanco, Eugenia Negredo, José L. Casado, Pilar Vizcarra, and MSD
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0301 basic medicine ,Oncology ,Male ,Time Factors ,Sustained Virologic Response ,Resistance ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Simplification ,0302 clinical medicine ,030212 general & internal medicine ,Treatment Failure ,Darunavir ,Drug Substitution ,General Medicine ,Middle Aged ,Drug Combinations ,Infectious Diseases ,Drug Therapy, Combination ,Female ,medicine.drug ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,Dual therapy ,Genotype ,030106 microbiology ,CD4-CD8 Ratio ,Microbial Sensitivity Tests ,03 medical and health sciences ,Young Adult ,Internal medicine ,Raltegravir Potassium ,Drug Resistance, Viral ,medicine ,Humans ,Protease inhibitor (pharmacology) ,HIV Integrase Inhibitors ,Aged ,Retrospective Studies ,Ritonavir ,General Immunology and Microbiology ,business.industry ,HIV Protease Inhibitors ,Raltegravir ,Mutation ,Switching ,HIV-1 ,Cobicistat ,business - Abstract
[Background]: Little is known about the impact of baseline resistance-associated mutations (RAMs) on the outcomes of alternative therapeutic strategies such as dual regimens. We assessed the efficacy of boosted darunavir plus raltegravir (DRV + RAL) dual regimen as a simplification strategy in virologically suppressed patients with protease inhibitors RAMs., [Methods]: Retrospective, multicentre study on the evolution of 228 heavily pretreated patients who switched to boosted DRV + RAL according to genotypic sensitivity score (GSS). Patients were classified as full susceptible (GSS = 2; n = 177), or with reduced darunavir susceptibility (GSS < 2; n = 51)., [Results]: Median (range) number of prior antiretroviral regimens was 9 (6–14), with a median (range) of 2 (1–3), 4 (3–6), and 5 (2–9) major mutations to non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. The median time of virological suppression before simplification was 49 months (IQR 39.8–63.5). Patients with reduced darunavir GSS showed a higher number of protease inhibitors-RAMs (9.3 vs 4.5, p, [Conclusions]: Treatment simplification to a dual regimen of boosted DRV + RAL after long-term virological suppression was not associated with a high risk of treatment failure, even in patients harbouring protease inhibitors-resistant HIV infection., This study was supported by the MSD Investigator-Initiated Studies Program (MISP) under grant number 57180.
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- 2020
16. How well are we performing the initial assessment of HIV-positive patients? Results from a multicentre cohort in Spain
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Montserrat Sanmartí Vilamala, Nuria Espinosa, Inés Suárez-García, Federico Pulido, Eva Calabuig, Alfonso Cabello-Ubeda, Berta Pernas, Víctor Asensi Álvarez, INMA JARRIN, Andrés Navarro Ruiz, Ignacio De Los Santos Gil, Esther Rodríguez-Gallego, Pedro Herranz, Juan A. Pineda, Paloma Gijon, Mar Masiá, Roberto Muga, Mariona Xercavins, Livia Giner, LUZ MARTÍN CARBONERO, Ignacio Pérez Valero, EVA POVEDA, DAVID DALMAU, Montserrat Vargas Laguna, Juan González-García, Mar Vera, ALICIA GONZALEZ-BAEZA, José A. Oteo, Eduardo Malmierca Corral, Maria Jose Amengual, Francisco Arnalich Fernandez, Jose Maria García de Lomas Guerrero, Vicente Boix, Rocio Montejano Sanchez, Maria José Mellado Peña, Xavier Barber, Marta Montero, Sergio Padilla, Esperanza Merino de Lucas, Anna Rull, PATRICIA GONZALEZ-RUANO, Rosa De Miguel Buckley, Mª Ángeles Muñoz-Fernández, Angeles Jaen, José Ignacio Bernardino, Cristina Moreno Prieto, Alfonso Del Arco Jiménez, Luis Fernando Lopez.Cortes, Rafael Mican, Rafael Rubio García, Félix Gutiérrez, Eulalia Valle-Garay, Marta Fernández-González, Juan Berenguer, Asuncion Hernando, Víctor Hontañón Antoñana, Jose Arribas, Mª Jesus Perez Elias, JOSE ALBERTO GARCIA GOMEZ, Instituto de Salud Carlos III, and European Commission
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Sida ,Enfermedad transmisible ,HIV Infections ,Practice guidelines ,Men who have sex with men ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Syphilis ,Latent tuberculosis ,business.industry ,Health Policy ,Health care quality assurance ,virus diseases ,Hepatitis A ,Health care quality indicators ,Serodiagnóstico del SIDA ,Viral Load ,HIV infection ,medicine.disease ,Hepatitis B ,030112 virology ,Hepatitis C ,CD4 Lymphocyte Count ,Infectious Diseases ,Logistic Models ,Serology ,Spain ,Cohort ,Practice Guidelines as Topic ,Cohort studies ,Female ,Guideline Adherence ,business ,Viral load ,Atención a la salud ,Cohort study - Abstract
[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).
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- 2019
17. Response to a reinforced hepatitis B vaccination scheme in HIV-infected patients under real-life conditions
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Alicia Gutierrez-Valencia, Luis F. López-Cortés, Silvia Llaves-Flores, Pompeyo Viciana, Karin Neukam, Nuria Espinosa, Red Española de Investigación en SIDA, and Instituto de Salud Carlos III
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Adult ,Male ,medicine.medical_specialty ,Hepatitis B virus ,030231 tropical medicine ,CD4-CD8 Ratio ,Immunization, Secondary ,HIV Infections ,medicine.disease_cause ,Immunocompromised Host ,03 medical and health sciences ,0302 clinical medicine ,CD4/CD8 ratio ,Interquartile range ,Antiretroviral Therapy, Highly Active ,Internal medicine ,Humans ,Medicine ,Hiv infected patients ,030212 general & internal medicine ,Immunization Schedule ,Retrospective Studies ,General Veterinary ,General Immunology and Microbiology ,Coinfection ,business.industry ,Vaccination ,Public Health, Environmental and Occupational Health ,virus diseases ,HIV ,Odds ratio ,Middle Aged ,Viral Load ,Hepatitis B ,medicine.disease ,Confidence interval ,digestive system diseases ,CD4 Lymphocyte Count ,Infectious Diseases ,ROC Curve ,Spain ,Molecular Medicine ,Female ,business - Abstract
[Background] HIV-infected patients are at risk of hepatitis B virus (HBV) coinfection, however, respond worse to HBV vaccination (HBV-V) than immunocompetent adults. This study aimed to determine the response to reinforced HBV-V in HIV-infected subjects under real-life conditions., [Methods] HIV-infected patients followed at a Spanish University Hospital who were seronegative for HBV and who received three double-doses (40 µL) of HBV-V at 0, 1 and 2 months were included. Response to HBV-V was defined as HBV surface antibody concentration of ≥10 IU/L 1–12 months after the last HBV-V dose., [Results] Of 332 patients included in the study, 256 (77.1%) showed response to HBV-V. Median (interquartile range) CD4+/CD8+ ratio among the responders was 0.75 (0.52–1.01) versus 0.61 (0.38–0.84) among the non-responders (p = 0.002). Independent predictors for HBV-V response were: female gender [adjusted odds ratio (AOR): 6.240; 95% confidence interval (95%CI): 1.954–19.925; p = 0.002]; non-smoking [AOR: 2.151; 95%CI: 1.243–3.721; p = 0.006]; a CD4+/CD8+ ratio ≥0.67 [AOR: 2.580; 95%CI: 1.209–5.505; p = 0.014] and baseline HIV-RNA ≤50 copies/mL [AOR: 2.049; 95%CI: 1.098–3.824; p = 0.024]., [Conclusion] Accelerated administration of three double-doses results in considerable high, however still suboptimal, response rates to HBV-V in HIV-infected patients in the clinical practice. A fourth dose should be considered., This work was partially funded by the Plan Nacional R+D+I and Red de Investigación en SIDA [grant number RD16/0025/0020-ISCIII-FEDER]. K.N. is the recipient of a Miguel Servet research grant [grant number CPII18/00033] from the Instituto de Salud Carlos III.
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- 2019
18. Pseudo skin flash on VMAT in breast radiotherapy: Optimization of virtual bolus thickness and HU values
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Nuria Jornet, Pablo Carrasco, María Lizondo, Anna Coral, Artur Latorre-Musoll, Montserrat Ribas, and Nuria Espinosa
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Biophysics ,General Physics and Astronomy ,Patient positioning ,Breast Neoplasms ,Breast radiotherapy ,Computed tomography ,030218 nuclear medicine & medical imaging ,User-Computer Interface ,03 medical and health sciences ,Skin-flash tool ,0302 clinical medicine ,Bolus (medicine) ,Hounsfield scale ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Radiation treatment planning ,Skin ,Volumetric arc therapy ,medicine.diagnostic_test ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Isocenter ,General Medicine ,Volumetric modulated arc therapy ,030220 oncology & carcinogenesis ,Radiotherapy, Intensity-Modulated ,Tomography, X-Ray Computed ,business ,Nuclear medicine - Abstract
Purpose: Optimisation strategies for volumetric modulated arc therapy (VMAT) in most treatment planning systems for breast cancer do not account for patient positioning, breathing, or anatomical changes. To overcome this limitation, a pseudo-skin flash strategy using a virtual bolus has been proposed. Using this strategy, we determined optimal thickness and value of Hounsfield units (HU) assigned to the virtual bolus to ensure adequate CTV irradiation. Materials and methods: We modified the original computed tomography data (CT0) by adding combinations of thicknesses and densities of a virtual bolus on PTVs (CT') of seven bilateral breast cancer patients. Using a single optimization objective template, we obtained a VMAT plan on CT' and recalculated this on the CT0. Optimal CT' parameters were defined as those that minimized dose differences between CT' and CT0 plans regarding PTV and OAR dose-volume parameters. We studied bolus parameters regarding robustness by shifting the isocenter 5 and 10 mm in the breathing direction for each CT0 plan. Results: The minimal dosimetric impact was between - 400 and - 600 HU depending on bolus thickness. OARs doses were not significantly affected. Best robustness was found for - 500 HU and 15 mm bolus thickness against shifts of up to 10 mm in the breathing direction. Conclusion: Our results support a bolus thickness equal to the CTV-PTV margin plus 5 mm and a virtual bolus HU value around - 500 and - 400 depending on the bolus thickness chosen. These findings could play a useful role in maximising robustness and minimising the need for plan renormalization.
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- 2019
19. High-risk human papilloma vrus testing improves diagnostic performance to predict moderate-to high-grade anal Intraepithelial neoplasia in human immunodeficiency virus-infected men who have xex with men in low-to-absent cytological abnormalities
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Luis F. López-Cortés, Yusnelkis Milanés-Guisado, Ana Domínguez Castaño, Karin Neukam, Pompeyo Viciana, María Fontillón, Cesar Sotomayor, Nuria Espinosa, Instituto de Salud Carlos III, European Commission, and Red Española de Investigación en SIDA
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Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Human papillomavirus ,Biopsy ,Cytodiagnosis ,HIV Infections ,Risk Assessment ,Sensitivity and Specificity ,Gastroenterology ,Men who have sex with men ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cytology ,Odds Ratio ,medicine ,Humans ,030212 general & internal medicine ,Homosexuality, Male ,Papillomaviridae ,Neoplasm Staging ,Squamous intraepithelial lesions ,medicine.diagnostic_test ,Proctoscopes ,business.industry ,Papillomavirus Infections ,Disease Management ,Reproducibility of Results ,Anoscopy ,virus diseases ,Middle Aged ,Anus Neoplasms ,Anus ,Anal liquid-based cytology ,Confidence interval ,HIV-infected men who have sex with men ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Concomitant ,Cohort ,Neoplasm Grading ,Diagnostic performance ,business ,Algorithms ,Carcinoma in Situ - Abstract
[Background]: Screening methods for anal squamous intraepithelial lesions (SILs) are suboptimal. We aimed to determine the diagnostic performance of a composite endpoint comprising anal liquid-based cytology (aLBC) and high-risk human papillomavirus (HR-HPV) testing to predict histological high-grade SILs (hHSILs). [Methods]: From the SeVIHanal cohort, human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) who had an aLBC with concomitant HR-HPV testing were included. hHSILs were determined by high-resolution anoscopy (HRA)-guided biopsy. [Results]: A total of 705 visits obtained from 426 patients were included. The prevalence of HR-HPV among aLBC results were 51.9% (133/215) normal, 87.9% (20/232) low-grade SILs (LSILs), and 90.9% (149/164) high-grade SILs; P (linear association) normal/noHR-HPV> (10%) and >LSIL/noHR-HPV> (4%). The prognostic values (95% confidence interval) for HR-HPV to predict hHSILs in normal cytology were positive predictive value (PPV), 29.3% (25.6%-33.3%); negative predictive value (NPV), 90.2% (82.8%-94.7%); sensitivity, 83% (69.2%-92.4%); and specificity, 44.1% (36.4%-51.9%). Corresponding figures for cytologic LSILs were PPV, 39.2% (37.4%-41.1%); NPV, 96.4% (78.9%-99.5%); sensitivity, 98.8% (93.3%-99.9%); and specificity, 17.9% (12.1%-24.9%). A positive interaction and a synergistic effect for the composite endpoint were observed (relative excess risk = 1.50, attributable proportion of histological results to interaction = 0.17, synergy index = 1.24). [Conclusions]: HRA should not be indicated in the setting of LSILs/noHR-HPV following aLBC-based screening. In contrast, HIV-infected MSM with normal aLBC/HR-HPV infection should be considered for HRA. Clinical Trials Registration: NCT03713229., This work was supported by the Plan Nacional R+D+I and the Red de Investigación en SIDA (grant RD16/0025/0020-ISCIII-FEDER). K. N. is the recipient of a Miguel Servet II contract by the Instituto de Salud Carlos III (number CPII18/00033).
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- 2019
20. Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice
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CoRIS, Melchor Riera, J.L. Gómez-Sirvent, Nuria Espinosa, Joaquim Peraire, Julián Olalla, Natalia Chueca, Carlos Guerrero-Beltran, Silvia García-Bujalance, Mónica García-Álvarez, David Dalmau, Adrian Curran, David Vinuesa, Arkaitz Imaz, María J Pérez-Elías, Eva Poveda, Antonio Aguilera, José Ramón Blanco, Adolfo de Salazar, Paz Casas, Gemma Navarro, Irene Portilla, Félix Gutiérrez, Jesús Santos, Carlos Galera, Marta Álvarez, Carmen Rodríguez, José Miguel Molina, Federico García, Lucio García-Fraile, José Antonio Iribarren, and Beatriz Pierola
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,030106 microbiology ,Integrase inhibitor ,HIV Infections ,Drug resistance ,Emtricitabine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Abacavir ,Internal medicine ,Drug Resistance, Viral ,medicine ,Prevalence ,Humans ,Pharmacology (medical) ,Public Health Surveillance ,030212 general & internal medicine ,HIV Integrase Inhibitors ,Aged ,Pharmacology ,Bictegravir ,business.industry ,Elvitegravir ,Middle Aged ,Raltegravir ,Infectious Diseases ,chemistry ,Spain ,Dolutegravir ,HIV-1 ,Female ,business ,medicine.drug - Abstract
Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. Methods: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. Results: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/ lamivudine was 1.7%, 1.9% and 0.7%, respectively. Conclusions: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
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- 2019
21. Parenteral drug use as the main barrier to hepatitis C treatment uptake in HIV-infected patients
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Dolores Merino, María Amparo Gómez-Vidal, Antonio Rivero, María Paniagua-García, Antonio Rivero-Juárez, Nuria Espinosa, J. Perez‐Stachowski, M. Castaño‐Carracedo, L. Muñoz‐Medina, Juan Macías, Elisa Fernández-Fuertes, Francisco Téllez, Antonio Collado, Jesús Santos, A. Zapata‐Lopez, Ministerio de Sanidad (España), Instituto de Salud Carlos III, and European Commission
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Longitudinal study ,genetic structures ,Hepatitis C virus ,Population ,HIV Infections ,medicine.disease_cause ,Antiviral Agents ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Longitudinal Studies ,Prospective Studies ,Barrier to treatment ,education ,Substance Abuse, Intravenous ,Aged ,Opioid substitution therapy ,Aged, 80 and over ,education.field_of_study ,business.industry ,Coinfection ,Health Policy ,virus diseases ,HIV ,Hepatitis C ,Odds ratio ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,030112 virology ,Confidence interval ,Drug Utilization ,Infectious Diseases ,Cohort ,Population study ,Female ,Direct‐acting antiviral treatment ,business ,People who inject drugs - Abstract
[Objectives]: Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV-coinfected patients., [Methods]: A prospective longitudinal study was carried out. HIV-infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct-acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow-up and those who were not., [Results]: Of the 15 556 HIV-infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow-up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment-naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST-PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST-PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409–0.746) and recent PWID (OR 0.019; 95% CI 0.004–0.087) were identified as independent factors associated with low odds of treatment implementation., [Conclusions]: We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years., This work was supported by the Ministerio de Sanidad (RD12/0017/0012) integrated in the Plan Nacional de I+D+I, and cofinanced by the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI15/01017), and the Red de Investigación en SIDA de España ISCIII‐RETIC (grant number: RD16/0025/0034).
- Published
- 2018
22. Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before–After Study (CortiCOVID Study)
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Maria Isabel Asensio-Cruz, Michelle Espinosa-Solano, Julia Praena-Segovia, Jose Molina Gil-Bermejo, Marta Ferrer-Galvan, José Manuel Lomas, María Paniagua-García, Elisa Cordero, Demetrio Gonzalez-Vergara, Manuel Garcia-Gutierrez, Macarena Borrero-Rodriguez, Alejandro Palomo, María Dolores Navarro-Amuedo, Manuela Aguilar-Guisado, Manuel Poyato, Cristina Roca-Oporto, Luis Jara-Palomares, Cesar Sotomayor, Candela Caballero-Eraso, and Nuria Espinosa
- Subjects
medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Tertiary referral hospital ,Dexamethasone ,Diseases of the respiratory system ,Internal medicine ,Neumonía ,medicine ,Intubation ,RC705-779 ,business.industry ,Standard treatment ,COVID-19 ,Pneumonia ,Odds ratio ,Dexametasona ,medicine.disease ,Confidence interval ,Severe acute respiratory syndrome ,Síndrome de distrés respiratorio agudo ,Methylprednisolone ,Corticosteroid ,Original Article ,business ,medicine.drug - Abstract
Introduction: The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods: A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results: A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5–21.8] days vs. 29 [23–31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions: In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode. Resumen: Introducción: El uso de corticosteroides sistémicos en pacientes gravemente enfermos por enfermedad coronavírica de 2019 (covid-19) es controvertido. Nuestro objetivo fue evaluar la eficacia y la seguridad de los pulsos de corticoesteroides en los pacientes con neumonía por covid-19. Métodos: Se realizó un ensayo cuasiexperimental, tipo antes y después, en un hospital terciario de referencia que incluyó a pacientes ingresados por neumonía asociada a covid-19. El protocolo de tratamiento estándar incluía un tratamiento antiviral dirigido contra el virus de la covid-19 desde el 23 de marzo de 2020 y añadió pulsos de metilprednisolona desde el 30 de marzo de 2020. El resultado primario fue un criterio combinado compuesto por la intubación orotraqueal y el fallecimiento durante los siguientes siete días. Resultados: Se incluyó un total de 24 pacientes. El protocolo de tratamiento (antes de la intervención) se prescribió en 14 pacientes, mientras que 10 recibieron el protocolo de tratamiento además de los pulsos de metilprednisolona (después de la intervención). La edad media de los pacientes fue de 64,5 años y el 83,3% de los pacientes eran hombres. El resultado combinado primario tuvo lugar en 13 pacientes (92,9%) que recibieron el protocolo de tratamiento frente a 2 pacientes (20%) que recibieron los pulsos de metilprednisolona (odds ratio = 0,02; intervalo de confianza del 95% = 0,001-0,25; p = 0,019). La duración de la hospitalización en los supervivientes fue más corta en el grupo que recibió corticoesteroides (media = 14,5 [8,5-21,8] días frente a 29 [23-31] días, p = 0,003). No hubo diferencias en el desarrollo de infecciones entre ambos grupos. Hubo tres fallecimientos, ninguno de ellos en el grupo que recibió corticoesteroides. Conclusiones: En los pacientes con neumonía grave por covid-19, la administración de pulsos de metilprednisolona se asoció a unas tasas menores de intubación orotraqueal y/o muerte y a episodios de hospitalización más cortos.
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- 2021
23. Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir-vs. efavirenz-based antiretroviral therapy
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Consuelo Viladés, Nuria Espinosa, VERONICA ALBA ELVIRA, Jose-Ramon Blanco, Miriam Estebanez, Sergio Veloso Esteban, INMA JARRIN, Andrés Navarro Ruiz, Enrique Bernal Morell, Paloma Gijon, Mar Masiá, Livia Giner, Francesc Vidal, DAVID DALMAU, Montserrat Vargas Laguna, JUAN JOSE SIRVENT, Jesús Miguel López Dupla, Vicente Estrada, Maria Luisa Montes, Vicente Boix, Sergio Padilla, Esperanza Merino de Lucas, Dulcenombre Gomez-Garre, Susana Monge, Luis Fernando Lopez.Cortes, Jesus Mingorance, Rafael Rubio García, Félix Gutiérrez, Juan Berenguer, Cristina Gonzalez, Víctor Hontañón Antoñana, Jose Luis Casado, Jose Arribas, Mª Jesus Perez Elias, and Joaquín Portilla
- Subjects
Adult ,Cyclopropanes ,Male ,medicine.medical_specialty ,Efavirenz ,Bilirubin ,Atazanavir Sulfate ,HIV Infections ,030204 cardiovascular system & hematology ,Gastroenterology ,Plasma ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,Peroxidase ,business.industry ,Health Policy ,Confidence interval ,Benzoxazines ,Atazanavir ,Lipoproteins, LDL ,Oxidative Stress ,Phospholipases A2 ,Regimen ,Infectious Diseases ,Anti-Retroviral Agents ,chemistry ,Alkynes ,Immunology ,Female ,Ritonavir ,business ,Biomarkers ,medicine.drug - Abstract
Objectives Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). Methods A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. Results After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. Conclusions When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
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- 2016
24. Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis
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Dolores Merino, Ana María Martínez-Sapiña, María Jesús Vivancos, Francisco Téllez, Antonio Rivero-Juárez, Lize Cuypers, Natalia Chueca, Teresa Aldámiz-Echevarría, Nuria Espinosa, Javier Salmerón, Ana Belén Pérez, Juan Carlos Alados, Anne-Mieke Vandamme, Juan A. Pineda, Federico García, and Víctor Hontañón
- Subjects
0301 basic medicine ,Male ,RNA viruses ,Molecular biology ,lcsh:Medicine ,Gene Sequencing ,HIV Infections ,Hepacivirus ,medicine.disease_cause ,Database and Informatics Methods ,Sequencing techniques ,Immunodeficiency Viruses ,Recurrence ,Genotype ,DNA sequencing ,lcsh:Science ,Phylogeny ,Pathology and laboratory medicine ,Data Management ,Multidisciplinary ,Transmission (medicine) ,Coinfection ,Hepatitis C virus ,Phylogenetic Analysis ,Hepatitis C ,Medical microbiology ,Phylogenetics ,Viruses ,Infectious diseases ,Pathogens ,Sequence Analysis ,Research Article ,medicine.medical_specialty ,Computer and Information Sciences ,Bioinformatics ,Genome, Viral ,Viral diseases ,Research and Analysis Methods ,Antiviral Agents ,Microbiology ,Virus ,03 medical and health sciences ,Pharmacotherapy ,Internal medicine ,Molecular genetics ,Retroviruses ,medicine ,Genetics ,Humans ,Evolutionary Systematics ,Homosexuality, Male ,Taxonomy ,Hepatitis ,Medicine and health sciences ,Evolutionary Biology ,Flaviviruses ,business.industry ,lcsh:R ,Lentivirus ,Organisms ,Viral pathogens ,Biology and Life Sciences ,HIV ,Human Genetics ,Hepatitis C, Chronic ,medicine.disease ,Hepatitis viruses ,Microbial pathogens ,030104 developmental biology ,Molecular biology techniques ,lcsh:Q ,business ,Sequence Alignment - Abstract
Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced. ispartof: PLOS ONE vol:13 issue:7 ispartof: location:United States status: published
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- 2018
25. Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients
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T. Martin, Jorge Vergas, Victoria Moreno, Juan Flores, Luis Force, J. C. Lopez Bernaldo de Quiros, Jordi Curto, Jhon Rojas, Antonio Ocampo, Bonaventura Clotet, Angela Camacho, José Antonio Iribarren, Arkaitz Imaz, J.L. Gómez-Sirvent, Nerea Rozas, Victor Asensi, Eulalia Valencia, Nuria Espinosa, Pablo Bachiller, Hernando Knobel, José Ramón Blanco, Pompeyo Viciana, Manuel Castaño, Iris A Perez, Daniel Podzamczer, and Universitat de Vic. Càtedra de la Sida i Malalties Relacionades
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Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Anti-HIV Agents ,HIV Infections ,Pharmacology ,Cohort Studies ,Young Adult ,Abacavir ,Antiretroviral Therapy, Highly Active ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Adverse effect ,Darunavir ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sulfonamides ,Ritonavir ,business.industry ,virus diseases ,Lamivudine ,Abacavir/Lamivudine ,Sida -- Tractament ,Middle Aged ,Viral Load ,Dideoxynucleosides ,Discontinuation ,Drug Combinations ,Regimen ,Treatment Outcome ,Infectious Diseases ,Spain ,HIV-1 ,Female ,business ,medicine.drug - Abstract
Objectives: To present clinical experience with a regimen including abacavir/lamivudine+darunavir/ritonavir in a cohort of HIV-1-infected patients. Methods: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine+darunavir/ritonavir from April 2008 to December 2010 and had at least one followup visit. The primary endpoint was HIV-1 viral load (VL) ,40 copies/mL at week 48. Results: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5–58.6) months, 79.8% were men, the median age was 47.1 (21.4– 80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm3 in naive patients and 393 cells/mm3 in experienced patients and the median VL was 4.80 and ,1.59 log copies/mL, respectively. Atweek 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL ,40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm3 in naive patients and +74.9 and +93 cells/mm3 in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. Conclusions: In our cohort, abacavir/lamivudine+darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.
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- 2014
26. Viral Kinetics in Semen With Different Antiretroviral Families in Treatment-Naive Human Immunodeficiency Virus-Infected Patients: A Randomized Trial
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Nuria Espinosa, Alicia Gutierrez-Valencia, Maria Trujillo-Rodriguez, Inmaculada Rivas-Jeremías, Pompeyo Viciana, Omar J. BenMarzouk-Hidalgo, Luis F. López-Cortés, Tamara Fernandez-Magdaleno, [Gutierrez-Valencia, Alicia] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Benmarzouk-Hidalgo, Omar J.] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Rivas-Jeremias, Inmaculada] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Espinosa, Nuria] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Trujillo-Rodriguez, Maria] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Fernandez-Magdaleno, Tamara] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Viciana, Pompeyo] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, [Lopez-Cortes, Luis F.] Univ Seville, Enfermedades Infecciosas Microbiol & Med Prevent, Inst Biomed Sevilla, Hosp Univ Virgen Rocio,CSIC, Seville, Spain, and Gilead Science
- Subjects
0301 basic medicine ,Microbiology (medical) ,antiretroviral treatment ,Adult ,Male ,030106 microbiology ,Co-formulated elvitegravir ,HIV Infections ,Emtricitabine ,Hiv-1 rna ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,Wild-type ,Semen ,Blood plasma ,medicine ,Humans ,Darunavir ,Compartments ,business.industry ,Elvitegravir ,Cobicistat ,Rilpivirine ,Double-blind ,Initial treatment ,semen ,Middle Aged ,Viral Load ,Virology ,Kinetics ,Infectious Diseases ,Blood ,chemistry ,male genital tract ,Anti-Retroviral Agents ,Dolutegravir ,HIV-1 ,RNA, Viral ,Ritonavir ,business ,Viral load ,medicine.drug - Abstract
Background There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of human immunodeficiency virus (HIV) RNA decay in semen. Objective To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma (SP) of treatment-naive HIV-infected patients. Methods Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-disoproxil fumarate (DF) plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv). The primary endpoint was the proportion of participants with undetectable HIV-RNA in SP at week 12. HIV type 1 (HIV-1) RNA was measured in paired SP and blood plasma (BP) at baseline and after 1, 2, 4, 6, 8, 12, 18, and 24 weeks. Elvitegravir (EVG), RPV, and darunavir (DRV) concentrations were quantified by the liquid chromatography-tandem mass spectrometry method. Results In SP, the HIV-RNA decay rate with RPV was as fast as with EVGcobi; by week 12, all participants in the RPV and the EVGcobi groups reached an undetectable viral load but only 58.3% in the DRVrtv arm (P = .003). The highest SP/BP drug concentration ratio was for EVG (0.43), followed-up by RPV (0.19), and DRV (0.10). For both EVG and RPV, the SP concentrations exceeded >2-fold the protein binding-adjusted EC90 for wild-type HIV-1; for DRV, only 33.7% of the SP showed concentrations above the protein binding-adjusted EC90. Conclusions In SP, both RPV and EVGcobi, associated to tenofovir-DF and emtricitabine, behave similarly and achieve an undetectable viral load much faster than DRVrtv. Registration European Medical Agency (No. EudraCT: 2014-001348-39).
- Published
- 2016
27. Role of Ritonavir in the Drug Interactions Between Telaprevir and Ritonavir-Boosted Atazanavir
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Nuria Espinosa, Juan R. Castillo-Ferrando, Alicia Gutierrez-Valencia, Pompeyo Viciana, Rosa Ruiz-Valderas, Almudena Torres-Cornejo, and Luis F. López-Cortés
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Adult ,Male ,Microbiology (medical) ,Pyridines ,Hepatitis C virus ,Atazanavir Sulfate ,Cmax ,Alpha interferon ,HIV Infections ,Pharmacology ,medicine.disease_cause ,Antiviral Agents ,Mass Spectrometry ,Telaprevir ,Plasma ,chemistry.chemical_compound ,Pharmacokinetics ,Ribavirin ,medicine ,Humans ,Drug Interactions ,Ritonavir ,business.industry ,Interferon-alpha ,Hepatitis C, Chronic ,Middle Aged ,Atazanavir ,Infectious Diseases ,chemistry ,Drug Therapy, Combination ,business ,Oligopeptides ,Chromatography, Liquid ,medicine.drug - Abstract
Background Detrimental bidirectional pharmacokinetic interactions have been observed when telaprevir (TVR) and ritonavir (RTV)-boosted human immunodeficiency virus (HIV) protease inhibitors are coadministered in healthy volunteers. Our aim was to evaluate the role of RTV in the bidirectional TVR and atazanavir (ATV) interactions. Method An open-label, sequential study was carried out in hepatitis C virus (HCV)/HIV-coinfected patients on a RTV-boosted ATV-based (ATVr) antiretroviral regimen (300/100 mg every 24 hours) and triple therapy for chronic C hepatitis genotype 1 (TVR, 1125 mg every 12 hours, pegylated interferon-alpha and ribavirin). Pharmacokinetic profiles were acquired before and after switching from ATVr to unboosted ATV (200 mg every 12 hours). The plasma levels of both drugs were determined by liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis and compared by geometric mean ratios and their 90% confidence intervals. Results Fourteen white HCV/HIV-coinfected males were enrolled in this study. After RTV was withdrawn, the TVR AUC(0-12) (area under the concentration-time curve), maximum concentration (C(max)), and minimum concentration (C(min)) values increased by 19% (7%-30%), 12% (0.9%-29%), and 18% (2%-34%), respectively, without any changes in the TVR terminal half-life. The ATV AUC(0-12), C(max), and C(min) values were 39% (13%-66%), 19% (8%-59%), and 48% (1%-96%) higher, respectively, with a significantly shorter terminal half-life (22.6 hours vs 10.4 hours). Conclusions RTV is responsible for the adverse interactions that occur when TVR and ATVr are administered together, possibly by influencing either the absorption phase or first-pass metabolism of TVR. The boost effect of TVR on ATV exposure is higher than on RTV, despite its shorter terminal half-life. The coadministration of TVR and unboosted ATV results in increased exposure of both drugs compared with their coadministration with RTV. Clinical trials registration ClinicalTrials.gov: NCT01818856. European Medicines Agency EudraCT no. 2012-002515-25.
- Published
- 2013
28. The changing etiology of fever of intermediate duration
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Amalia Martín, Elías Cañas, Pompeyo Viciana, Nuria Espinosa, Máximo Bernabeu-Wittel, and Jerónimo Pachón
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Adult ,Male ,Microbiology (medical) ,Gynecology ,medicine.medical_specialty ,Time Factors ,Fever ,business.industry ,medicine ,Humans ,Female ,Prospective Studies ,business - Abstract
Introduccion La fiebre de duracion intermedia (FDI) es una causa importante de fiebre. Las etiologias mas importantes no estan bien definidas en la actualidad. Metodos Estudio prospectivo de los casos de FDI atendidos entre 1983�1989 y 2004�2005. Se realizaron cultivos y estudios serologicos para la deteccion de Brucella melitensis, Coxiella burnetii, Rickettsia typhi, Rickettsia conorii, citomegalovirus y virus de Epstein-Barr en todos los pacientes. Se llevaron a cabo otros estudios microbiologicos, serologicos, radiologicos y pruebas invasivas adicionales segun el criterio del clinico responsable. Resultados En el periodo de 1983 a 1989 se incluyeron 505 pacientes y 179 desde 2004 a 2005. Se alcanzo un diagnostico etiologico en 410 (81,1%) y 109 (60,9%), respectivamente. La causa de FDI fue infecciosa en 389 pacientes del primer periodo (94,8% del total de pacientes con diagnostico etiologico) y 92 del segundo (84,4%). La mayoria fueron infecciones sistemicas, 328 (80%) en 1983�1989 y 74 (67,8%) en 2004�2005, seguidas de infecciones focales, 9,5% y 16,5%, respectivamente. La fiebre Q fue la etiologia mas frecuente en ambos periodos. En 2004�2005, la brucelosis disminuyo mientras que la infeccion por el VIH se mostro como una causa emergente de FDI. El origen de la FDI fue no infeccioso en el 5,1% y el 15,5% de los casos, respectivamente. Conclusiones La fiebre Q es la causa mas frecuente de FDI en el sur de Espana. Son necesarios estudios prospectivos mas amplios para identificar los cambios en el espectro etiologico de esta entidad. Infecciones virales, como la infeccion por el VIH, deben ser contempladas como causa de FDI.
- Published
- 2010
29. High efficacy of resistance guided retreatment of Genotype 3 in real life
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JM Salmerón, Juan Carlos Alados Arboledas, Juan Manuel Pascasio, A. Poyato, A. Sánchez, Jose Miguel Rosales Zabal, José Hernández-Quero, A.D.L.I. Salgado, Dolores Merino, B.B. Carral, Miguel A. Casado, F.G.D.A. Clotilde, F.M. Jimenez, M.J. Álvarez-Ossorio, F.T. Pérez, C. Delgado, Federico García, Miguel Jimenez, J. De Juan, Nuria Espinosa, A.R.C. Romacho, and A.B.P. Jimenez
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Oncology ,medicine.medical_specialty ,Hepatology ,Resistance (ecology) ,business.industry ,Internal medicine ,Genotype ,medicine ,In real life ,business - Published
- 2018
30. Tunneled hemodialysis catheter-related bloodstream infections: a prospective multicenter cohort study from Spain
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Nuria Espinosa, M José Marco Guerrero, Ma José Ríos-Villegas, José Miguel Cisneros, Rafael Luque Márquez, Yolanda Blanco, Jose Ibeas, and Almudena Martín-Peña
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Adult ,Male ,medicine.medical_specialty ,Catheterization, Central Venous ,Time Factors ,medicine.medical_treatment ,Hemodialysis Catheter ,Kaplan-Meier Estimate ,Risk Assessment ,Young Adult ,Catheters, Indwelling ,Renal Dialysis ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Humans ,Prospective Studies ,Intensive care medicine ,Prospective cohort study ,Gram-Positive Bacterial Infections ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Incidence ,Middle Aged ,Prognosis ,Multicenter study ,Nephrology ,Spain ,Catheter-Related Infections ,Multivariate Analysis ,Etiology ,Surgery ,Female ,Hemodialysis ,business ,Cohort study - Abstract
Purpose Catheter-related bloodstream infections (CRBSI) are common among patients undergoing long-term hemodialysis (HD) worldwide. The aim of this study was look into the incidence, epidemiology, and risk factors for CRBSI in four medical centers and Spanish dialysis facilities following a common protocol for insertion and management of tunneled hemodialysis catheters (THCs). Methods. Prospective study including all THCs inserted from September-04 to October-05. Follow-up was from THC insertion to its withdrawal, onset of CRBSI or end of study. Data of all THCs, CRBSI episodes, and catheter complications were collected. A descriptive analysis of CRBSI incidence and etiology and multivariate Cox regression to identify risk factors for CRBSI was performed. Results. A total of 130 THCs in 123 patients were inserted. There were 34 879 catheter-days. Twelve CRBSI in 11 patients with a CRBSI rate of 0.34/1000 catheter-days were recorded. CRBSI was caused by gram-positive coccus in 91.7% of the cases. Vascular cause of renal disease (HR 25.5 CI95% 5.5–117.2), and a previous THC (HR 5.1 CI95% 1.3–19.1) were identified as risk factors for CRBSI. CRBSI were satisfactorily resolved in 83.3% of the cases. Overall mortality was 14.6% (18/123), in two cases (2/11) death occurred within 30 days after CRBSI onset. Conclusions. Although some factors, such as vascular cause of renal disease and previous THC medical history, have been related to the onset of tunneled catheter-related bloodstream infections, the incidence of these bacteremia, mainly produced by gram-positive coccus, is low among hemodialysis patients and the mortality rate is not high.
- Published
- 2011
31. [Laterocervical tumor and fever]
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Nuria, Espinosa, Nieves, Margarit, Rafael, Luque, and Arístides, de Alarcón
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Arthritis, Infectious ,Fever ,Myositis ,Shoulder Joint ,Humans ,Female ,Middle Aged ,Staphylococcal Infections - Published
- 2006
32. Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected patients. Preliminary results of the hEPAtic Study
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Marta Díaz-Menéndez, Francisco Jesús Vera-Méndez, Francisco Téllez, Karin Neukam, Antonio Collado, Inés Pérez-Camacho, Josefa Ruiz-Morales, María José Ríos, Antonio Rivero-Juárez, Juan A. Pineda, Ana Carrero, Nuria Espinosa, Marcial Delgado-Fernández, Dolores Merino, and Ana Gómez-Berrocal
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medicine.medical_specialty ,Pediatrics ,business.industry ,Incidence (epidemiology) ,Single tablet regimen ,Public Health, Environmental and Occupational Health ,Hepatitis C ,medicine.disease ,Confidence interval ,Discontinuation ,Clinical trial ,chemistry.chemical_compound ,Infectious Diseases ,Acquired immunodeficiency syndrome (AIDS) ,chemistry ,Internal medicine ,Rilpivirine ,Poster Sessions – Abstract P099 ,medicine ,business - Abstract
Introduction : Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub-population of HIV/HCV-coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low [1]. The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of clinical trials. Patients and Methods : This is a retrospective analysis of HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE. Results : Of the 191 patients included, 31 (16.2%) subjects were naive to ART. Eighty-seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI-sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir-boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1–Q3) follow-up was 5.79 (3.65–8.61) months for the cases and 11.44 (5.8–12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person-years versus 5.51/100 person-years [incidence rate difference (95% confidence interval): −1.88 (−9.95–6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r. Conclusions : The frequency of grade 3–4 TE associated with EPA in HIV/HCV-coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV-coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation. (Published: 2 November 2014) Citation : Neukam K et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19631 http://www.jiasociety.org/index.php/jias/article/view/19631 | http://dx.doi.org/10.7448/IAS.17.4.19631
- Published
- 2014
33. Tumoración laterocervical y fiebre
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Rafael Luque, Nieves Margarit, Arístides de Alarcón, and Nuria Espinosa
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Microbiology (medical) - Abstract
Mujer de 58 anos con antecedentes de diabetes mellitus tipo 2, en tratamiento con insulina y antidiabeticos orales, y excoriaciones por rascado secundarias a prurito generalizado de un ano de evolucion. Ingreso por dolor e inflamacion en region clavicular y laterocervical izquierdas, dolor a la movilizacion del miembro superior izquierdo sin limitacion funcional, y sensacion febril de 6 dias de evolucion. A la exploracion presentaba fiebre de 39 °C, se palpaba una tumefaccion en la articulacion esternoclavicular izquierda y una tumoracion dolorosa de bordes mal definidos en region laterocervical del mismo lado (fig. 1a). Se aprecian multiples excoriaciones en tronco y extremidades superiores (figs. 1b y 1c). La bioquimica sanguinea y el hemograma fueron normales salvo una velocidad de sedimentacion globular (VSG) de 115 mm. Los hemocultivos y el urocultivo fueron negativos. La tomografia computarizada (TC) del cuello mostraba un aumento de tamano del musculo esternocleidomastoideo (ECM) izquierdo con un area hipodensa en su interior sin refuerzo periferico tras administracion de contraste (fig. 2a) y una coleccion hipodensa alrededor de la articulacion con edema de partes blandas (fig. 2b).
- Published
- 2006
34. Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before–After Study (CortiCOVID Study) Uso de pulsos de metilprednisolona de repetición en adultos hospitalizados por neumonía y síndrome de distrés respiratorio agudo por COVID-19: un estudio preliminar de tipo antes-después (estudio CortiCOVID)
- Author
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Nuria Espinosa, Gonzalez-Vergara D, Ferrer-Galvan M, Asensio-Cruz M, Lomas J, Roca-Oporto C, Navarro-Amuedo M, Paniagua-Garcia M, Sotomayor C, and CortiCOVID-19 Team
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