Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions
2019
Evangelia-Georgia Kostaki | Andreas Flampouris | Timokratis Karamitros | 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 | Federico Garcia | 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 | Rafael Rubio | 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 | Félix Gutiérrez | 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 Berenguer | 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 | Francesc Vidal | 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 | David Dalmau | 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 | Santiago Moreno | 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 | Paz Casas | Marta Alvarez | Natalia Chueca | 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 | Vanessa Montero
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.
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