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1. Epidemiological, Clinical, and Microbiological Characteristics in a Large Series of Patients Affected by Dermacentor-Borne-Necrosis-Erythema-Lymphadenopathy from a Unique Centre from Spain

Author

Sonia Santibáñez, Aránzazu Portillo, Valvanera Ibarra, Paula Santibáñez, Luís Metola, Concepción García-García, Ana M. Palomar, Cristina Cervera-Acedo, Jorge Alba, José R. Blanco, and José A. Oteo

Subjects
DEBONEL, Dermacentor-borne-necrosis-erythema-lymphadenopathy, Dermacentor marginatus, ‘Candidatus Rickettsia rioja’, Rickettsia slovaca, Rickettsia raoultii, Medicine
Abstract

During recent decades, a tick-borne rickettsial syndrome, characterized by eschar and painful lymphadenopathy after Dermacentor marginatus-bite, has been described as an emerging rickettsiosis in Europe. Our group named it DEBONEL (Dermacentor-borne-necrosis-erythema-lymphadenopathy), regarding the vector and the main infection signs. Other groups called it TIBOLA (tick-borne-lymphadenophathy) and, later, SENLAT (scalp-eschar-and-neck-lymphadenopathy-after-tick-bite), expanding, in the latter, the etiological spectrum to other pathogens. Objective: To investigate the etiology of DEBONEL agents in our area, and to compare their epidemiological/clinical/microbiological characteristics. During 2001–2020, 216 patients clinically diagnosed of DEBONEL (the largest series from one center) in La Rioja (northern Spain) were examined. Rickettsia spp. were amplified in 14/104 (13.46%) blood samples, 69/142 (48.59%) eschar swabs, 7/7 (100%) biopsies, and 71/71 (100%) D. marginatus from patients. For samples in which Rickettsia was undetected, no other microorganisms were found. ‘Candidatus Rickettsia rioja’, Rickettsia slovaca, Rickettsia raoultii, and Rickettsia DmS1 genotype were detected in 91, 66, 4, and 3 patients, respectively. DEBONEL should be considered in patients with clinical manifestations herein described in areas associated to Dermacentor. The most frequently involved agent in our environment is ‘Ca. R. rioja’. The finding of Rickettsia sp. DmS1 in ticks attached to DEBONEL patients suggests the implication of other rickettsia genotypes.

Published
2022
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2. Beyond the effects of HIV infection and integrase inhibitors-based therapies on oral bacteriome

Author

Pablo Villoslada-Blanco, Patricia Pérez-Matute, Emma Recio-Fernández, María Íñiguez, Pilar Blanco-Navarrete, Luis Metola, Valvanera Ibarra, Jorge Alba, María de Toro, and José A. Oteo

Subjects
Medicine, Science
Abstract

Abstract Oral microbiome is the second largest microbial community in humans after gut. Human immunodeficiency virus (HIV) infection triggers an impairment of the immune system which could favour the growth and the colonization of pathogens in the oral cavity, and this dysbiosis has been associated with oral manifestations that worsen the quality of life of these patients. Antiretroviral therapy (ART) could also drive changes in specific oral bacterial taxa associated with such periodontal diseases. Integrase strand transfer inhibitors (INSTIs), therapy of choice in the treatment of naive HIV-patients, are able to reverse the impact of HIV infection on systemic inflammation, gut permeability, and gut bacterial diversity/richness. The objective of this study was to analyse the effects of HIV infection per se and INSTIs on salivary bacteriome composition, taking into consideration other factors such as smoking, that could also have a significant impact on oral microbiome. To accomplish this objective, 26 non-HIV-infected volunteers and 30 HIV-infected patients (15 naive and 15 under INSTIs-regimen) were recruited. Salivary samples were collected to measure lysozyme levels. Oral bacteriome composition was analysed using 16S rRNA gene sequencing. Naive HIV-infected patients showed statistically higher levels of lysozyme compared to controls (p

Published
2023
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3. Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome

Author

Pablo Villoslada-Blanco, Patricia Pérez-Matute, María Íñiguez, Emma Recio-Fernández, Daan Jansen, Lander De Coninck, Lila Close, Pilar Blanco-Navarrete, Luis Metola, Valvanera Ibarra, Jorge Alba, Jelle Matthijnssens, and José A. Oteo

Subjects
Medicine, Science
Abstract

Abstract Viruses are the most abundant components of the human gut microbiome with a significant impact on health and disease. The effects of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) are associated with a healthier gut. Thus, the objective of this work was to evaluate the effects of HIV infection and INSTIs on gut virome composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and their gut virome composition was analysed using shotgun sequencing. Bacteriophages were the most abundant and diverse viruses present in gut. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment. β-diversity of phages revealed that samples from HIV-infected patients clustered separately from those belonging to the control group. Differential abundant analysis showed an increase in phages belonging to Caudoviricetes class in the naive group and a decrease of Malgrandaviricetes class phages in the INSTIs-treated group compared to the control group. Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages. Our study describes for the first time the impact of HIV and INSTIs on gut virome and demonstrates that INSTIs-based treatments are able to partially restore gut dysbiosis at the viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

Published
2022
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4. Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS eventsResearch in context

Author

Javier Martínez-Sanz, Jorge Díaz-Álvarez, Marta Rosas, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemi Cabello, Julián Olalla, Santiago Moreno, Sergio Serrano-Villar, Inma Jarrín, David Dalmau, M. Luisa Navarro, M. Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M. Ángeles Muñoz-Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, Elba Mauleón, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez-Payá, Juan Carlos Rodríguez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrus, Verónica Pérez, Julia Portilla, Juan Luís Gómez, Jehovana Hernández, Ana López Lirola, Dácil García, Felicitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, M. Remedios Alemán, Víctor Asensi, María Eugenia Rivas Carmenado, Tomás Suarez-Zarracina, Federico Pulido, Otilia Bisbal, M. Asunción Hernando, David Rial, María de Lagarde, Octavio Arce, Adriana Pinto, Laura Bermejo, Mireia Santacreu, Roser Navarro, Candela Gonzalez, M. José Aramburu, Xabier Camino, Miguel Ángel von Wichmann, Miguel Ángel Goenaga, M. Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Lourdes Martínez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Vanessa Agullo, Javier Garcia Abellán, Reyes Pascual, Guillermo Telenti, Lucia Guillén, Ángela Botella, Roberto Muga, Arantza Sanvisens, Daniel Fuster, Isabel Gutierrez, Juan Carlos López, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Cristina Diez, Leire Pérez, Chiara Fanciulli, Saray Corral, Anna Martí, Joaquín Peraire, Consuelo Viladés, Montserrat Vargas, Montserrat Olona, Anna Rull, Verónica Alba, Elena Yeregui, Jenifer Masip, Graciano García-Pardo, Frederic Gómez Bertomeu, Sonia Espineira, Marta Montero, Sandra Cuéllar, Marino Blanes, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Inmaculada Segarra, Juan González-García, Ana Delgado, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García, Alicia González-Baeza, M. Luz Martín-Carbonero, Mario Mayoral, M. Jose Mellado, Rafael Esteban, Rocío Montejano, M. Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Guadalupe Rúa, Talía Sainz, Elena Sendagorta, Eulalia Valencia, Carmen Busca, Joanna Cano, Julen Cardiñanos, Rosa de Miguel, Jose Ramón Blanco, Laura Pérez-Martínez, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Piedad Arazo, Gloria Sampériz, Marina Martinez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Francesco Aiello, María Rivero, Beatriz Piérola, Maider Goikoetxea, María Gracia, Carlos Ibero, Estela Moreno, Jesús Repáraz, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaro, Belen Lopez Garcia, Ignacio de los Santos, Alejandro de los Santos, Jesús Sanz, Lucio García-Fraile, Enrique Martín, Ildefonso Sánchez-Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, Santos del Campo, José Luis Casado, Fernando Dronda, Ana Moreno, M. Jesús Pérez, Sergio Serrano, Ma Jesús Vivancos, Alejandro Vallejo, Matilde Sanchez, Jose Antonio Pérez-Molina, José Manuel Hermida, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Mónica Martínez, M. Carmen Villalba, Federico García, Clara Martínez, José Hernández, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Antonio Antela, Elena Losada, Melchor Riera, María Peñaranda, M. Angels Ribas, Antoni A. Campins, Mercedes Garcia-Gazalla, Francisco J. Fanjul, Javier Murillas, Francisco Homar, Helem H. Vilchez, Luisa Martin, Antoni Payeras, Jesús Santos, María López, Crisitina Gómez, Isabel Viciana, Rosario Palacios, Luis Fernando López-Cortés, Nuria Espinosa, Cristina Roca, Silvia Llaves, Juan Manuel Tiraboschi, Arkaitz Imaz, Ana Karina Silva, María Saumoy, Sofía Catalina Scévola, Adrián Curran, Vicenç Falcó, Jordi Navarro, Joaquin Burgos, Paula Suanzes, Jorge García, Vicente Descalzo, Patricia Álvarez, Bibiana Planas, Marta Sanchiz, Lucía Rodríguez, M José Sánchez, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luis Prada, Onofre Juan Martínez, Lorena Martinez, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, Antonio Jesús Sánchez Guirao, Alvaro Mena, Angeles Castro, Berta Pernas, Pilar Vázquez, Soledad López, Sofía Ibarra, Guillermo García, Josu Mirena, Oscar Luis Ferrero, Josefina López, M. Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo Lopez, Itxaso Lombide, Victor Polo, Joana de Miguel, Carlos Galera, Marian Fernández, Helena Albendin, Antonia Castillo, Asunción Iborra, Antonio Moreno, M. Angustias Merlos, Asunción Vidal, Concha Amador, Francisco Pasquau, Concepcion Gil, Jose Tomás Algado, Inés Suarez-García, Eduardo Malmierca, Patricia González-Ruano, M. Pilar Ruiz, José Francisco Pascual, Elena Sáez, Luz Balsalobre, M. Villa López, Mohamed Omar, Carmen Herrero, M. Amparo Gómez, Miguel Alberto de Zarraga, Desiré Pérez, Vicente Estrada, Nieves Sanz, Noemí Cabello, Jorge Vergas García, Maria Jose Núñez, Iñigo Sagastagoitia, Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto, Irene Carrillo, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, M. José Galindo, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Rivero Juárez, Pedro López, Isabel Machuca, Mario Frias, Ángela Camacho, Ignacio Pérez, Diana Corona, Miguel Cervero, Rafael Torres, Juan Antonio Pineda, Pilar Rincón, Juan Macías, Luis Miguel Real, Anais Corma, Alejandro Gonzalez-Serna, Alexandre Pérez, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, Lucía Patiño, Carlos Dueñas, Sara Gutiérrez, Elena Tapia, Cristina Novoa, Xjoylin Egües, and Pablo Telleria

Subjects
HIV, Non-AIDS events, Neoplasia, Cardiovascular event, CD4/CD8 ratio, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Published
2023
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5. Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

Author

José Ramón Santos, Maria Casadellà, Marc Noguera-Julian, Rafael Micán-Rivera, Pere Domingo, Antonio Antela, Joaquin Portilla, Jesús Sanz, Marta Montero-Alonso, Jordi Navarro, Mar Masiá, Nieves Valcarce-Pardeiro, Antonio Ocampo, Laura Pérez-Martínez, Coral García-Vallecillos, María Jesús Vivancos, Arkaitz Imaz, José Antonio Iribarren, José Hernández-Quero, Judit Villar-García, Pilar Barrufet, Roger Paredes, INSTINCT study group, Mariona Perera, Anna Chamorro, Cristina Miranda, Nástor Sánchez, Anna Garcı́á, Núria Pérez, Juan González Garcı́á, María del Mar Gutiérrez, María Gracia Mateo, Elena Losada, Sergio Reus, Vicente Boix, Diego Torrús, Esperanza Merino, Angela Gutiérrez Liarte, Adrià Curran, Félix Gutiérrez, Anna Mariño Callejo, Alvarez Diaz Hortensia, Antonio Ocampo Hermida, Celia Miralles, Laura Labajo Leal, Guillermo Pousada, José Ramon Blanco, José Antonio Oteo, Ibarra Valvanera, Mercedes Sanz, Luis Metola, Juan Pascua, Daniel Podzamczer, Camila Piatti, Maialen Ibarguren, Laia Arbones, Marta Ruiz, Sara Cervanntes, Helena Pera, Jessica Toro, Nuria Perez-Alvarez, and Anna Garcia

Subjects
HIV, integrase strand transfer inhibitors (INSTI), real-world study, raltegravir, elvitegravir, dolutegravir, Microbiology, QR1-502
Abstract

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir

Published
2023
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6. Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Author

Evangelia-Georgia Kostaki, Andreas Flampouris, Timokratis Karamitros, Natalia Chueca, Marta Alvarez, Paz Casas, Belen Alejos, Angelos Hatzakis, Federico Garcia, Dimitrios Paraskevis, CoRIS, Santiago Moreno, Inma Jarrín, David Dalmau, Maria Luisa Navarro, Maria Isabel González, Jose Luis Blanco, Rafael Rubio, Jose Antonio Iribarren, Félix Gutiérrez, Francesc Vidal, Juan Berenguer, Juan González, Belén Alejos, Victoria Hernando, Cristina Moreno, Carlos Iniesta, Luis Miguel Garcia Sousa, Nieves Sanz Perez, M Ángeles Muñoz-Fernández, Isabel María García-Merino, Irene Consuegra Fernández, Coral Gómez Rico, Jorge Gallego de la Fuente, Paula Palau Concejo, Joaquín Portilla, Esperanza Merino, Sergio Reus, Vicente Boix, Livia Giner, Carmen Gadea, Irene Portilla, María Pampliega, Marcos Díez, Juan Carlos Rodríguez, José Sánchez-Payá, Juan Luis Gómez, Jehovana Hernández, María Remedios Alemán, María del Mar Alonso, María Inmaculada Hernández, Felicitas Díaz-Flores, Dácil García, Ricardo Pelazas, Ana López Lirola, José Sanz Moreno, Alberto Arranz Caso, Cristina Hernández Gutiérrez, María Novella Mena, Federico Pulido, Otilia Bisbal, Asunción Hernando, Lourdes Domínguez, David Rial Crestelo, Laura Bermejo, Mireia Santacreu, José Antonio Iribarren, Julio Arrizabalaga, María José Aramburu, Xabier Camino, Francisco Rodríguez-Arrondo, Miguel Ángel von Wichmann, Lidia Pascual Tomé, Miguel Ángel Goenaga, Ma Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Aitziber Lizardi, Xabier Kortajarena, Mar Masiá, Sergio Padilla, Andrés Navarro, Fernando Montolio, Catalina Robledano, Joan Gregori Colomé, Araceli Adsuar, Rafael Pascual, Marta Fernández, Elena García, José Alberto García, Xavier Barber, Juan Carlos López Bernaldo de Quirós, Isabel Gutiérrez, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Francisco José Parras, Pascual Balsalobre, Cristina Diez, Leire Pérez Latorre, Joaquín Peraire, Consuelo Viladés, Sergio Veloso, Montserrat Vargas, Miguel López-Dupla, Montserrat Olona, Anna Rull, Esther Rodríguez-Gallego, Verónica Alba, Marta Montero Alonso, José López Aldeguer, Marino Blanes Juliá, María Tasias Pitarch, Iván Castro Hernández, Eva Calabuig Muñoz, Sandra Cuéllar Tovar, Miguel Salavert Lletí, Juan Fernández Navarro, Jose Miguel Molina, Juan González-garcia, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino de la Serna, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García López-Hortelano, Alicia González-Baeza, Maria Luz Martín-Carbonero, Mario Mayoral, Maria Jose Mellado, Rafael Esteban Micán, Rocio Montejano, María Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Talia Sainz, Elena Sendagorta, Natalia Stella Alcáriz, Eulalia Valencia, José Ramón Blanco, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Laura Pérez-Martínez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Jesús Repáraz, María Gracia Ruiz de Alda, María Teresa de León Cano, Beatriz Pierola Ruiz de Galarreta, Ignacio de los Santos, Jesús Sanz Sanz, Ana Salas Aparicio, Cristina Sarriá Cepeda, Lucio Garcia-Fraile Fraile, Enrique Martín Gayo, José Luis Casado, Fernando Dronda, Ana Moreno, María Jesús Pérez Elías, Cristina Gómez Ayerbe, Carolina Gutiérrez, Nadia Madrid, Santos del Campo Terrón, Paloma Martí, Uxua Ansa, Sergio Serrano, María Jesús Vivancos, Enrique Bernal, Alfredo Cano, Antonia Alcaraz García, Joaquín Bravo Urbieta, Ángeles Muñoz, Maria Jose Alcaraz, Maria del Carmen Villalba, Federico García, José Hernández, Alejandro Peña, Leopoldo Muñoz, David Vinuesa, Clara Martinez-Montes, Fernando García, Carlos Guerrero-Beltran, Jorge Del Romero, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Antonio Antela, Elena Losada, Antonio Aguilera, Melchor Riera, María Peñaranda, María Leyes, Ma Angels Ribas, Antoni A Campins, Carmen Vidal, Francisco Fanjul, Javier Murillas, Francisco Homar, Jesús Santos, Crisitina Gómez Ayerbe, Isabel Viciana, Rosario Palacios, Carmen María González, Pompeyo Viciana, Nuria Espinosa, Luis Fernando López-Cortés, Daniel Podzamczer, Elena Ferrer, Arkaitz Imaz, Juan Tiraboschi, Ana Silva, María Saumoy, Julián Olalla, Alfonso del Arco, Javier de la torre, José Luis Prada, José María García de Lomas Guerrero, Javier Pérez Stachowski, Concepción Amador, Onofre Juan Martínez, Francisco Jesús Vera, Lorena Martínez, Josefina García, Begoña Alcaraz, Amaya Jimeno, Angeles Castro Iglesias, Berta Pernas Souto, Alvaro Mena de Cea, Carlos Galera, Helena Albendin, Aurora Pérez, Asunción Iborra, Antonio Moreno, Maria Angustias Merlos, Asunción Vidal, Inés Suárez-García, Eduardo Malmierca, Patricia González-Ruano, Dolores Martín Rodrigo, Mohamed Omar Mohamed-Balghata, Juan A Pineda, Juan Macías, Miguel Thomson, Elena Delgado, Sonia Benito, and Vanessa Montero

Subjects
HIV-1, CRF02_AG, Spain, regional dispersal, spatiotemporal characteristics, Microbiology, QR1-502
Abstract

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.

Published
2019
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7. Gender differences for frailty in HIV-infected patients on stable antiretroviral therapy and with an undetectable viral load.

Author

José-Ramón Blanco, Inmaculada Barrio, Enrique Ramalle-Gómara, María Isabel Beltran, Valvanera Ibarra, Luis Metola, Mercedes Sanz, José A Oteo, Estrella Melús, and Lucía Antón

Subjects
Medicine, Science
Abstract

BackgroundPatients with HIV infection suffer from accelerated aging. In this context, frailty could be a relevant problem that aggravates the quality of life (QoL) and morbi-mortality of these patients. Our objective was to determine the prevalence of frailty and pre-frailty in HIV-infected patients in our cohort as well as their risk factors and QoL.MethodsThis was a prospective cross-sectional study of HIV-infected people aged ≥18 years on a stable antiretroviral regimen (ART) ≥1 year. Frailty was defined by ≥3 of 5 Fried's criteria: weight loss, low physical activity, exhaustion, weak grip strength and slow walking time. Variables related to sociodemographics, HIV infection, comorbidities, polypharmacy, and QoL were evaluated. Independent predictors of frailty were evaluated using collinearity in a multivariate logistic regression analyses (backward stepwise elimination).ResultsThe 248 people studied has a mean age of 49 years, 63.7% were male, and 81% were Caucasian. The prevalence of pre-frailty and fragility was 39.1% and 4.4%, respectively. The main route of HIV acquisition was heterosexual (47.2%). At the inclusion time 26.6% of the patients had AIDS events, 60.9% were anti-HCV negative, and 91.5% had HIV RNA 2 comorbidities, and 13.3% were receiving >5 non-HIV drugs. Frailty patients had a higher age (p 0.006), more sensitive deficits (visual or auditory) (p 0.002), a greater number of falls during the previous year (p 0.0001), a higher Charlson comorbidity index (p 0.001), and a higher VACS index (p 0.001). All comorbidities, excluding bone and liver, were significantly more frequent in fragile patients. The presence of >2 comorbidities and treatment with >5 drugs not related to HIV they were also more frequent in frail patienst (p 0.0001 and p 0.004, respectively). Independent predictors of pre-frailty/frailty in the multivariable analysis differ in men (VACS index, C-reactive protein [CRP], and falls) and women (CRP, AIDS, and menopause). Patients with pre-frailty/frailty had some indicator of a lower QoL.ConclusionFactors associated with pre-frailty/frailty in HIV-infected patients differ by gender, which should be considered when establishing measures for prevention. The role of menopause in the risk of pre-frailty/frailty warrants further investigations.

Published
2019
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