AUTHOR=Kostaki Evangelia-Georgia , Flampouris Andreas , Karamitros Timokratis , Chueca Natalia , Alvarez Marta , Casas Paz , Alejos Belen , Hatzakis Angelos , Garcia Federico , Paraskevis Dimitrios , CoRIS , Moreno Santiago , Jarrín Inma , Dalmau David , Luisa Navarro Maria , Isabel González Maria , Luis Blanco Jose , Garcia Federico , Rubio Rafael , Antonio Iribarren Jose , Gutiérrez Félix , Vidal Francesc , Berenguer Juan , González Juan , Alejos Belén , Hernando Victoria , Moreno Cristina , Iniesta Carlos , Miguel Garcia Sousa Luis , Sanz Perez Nieves , Ángeles Muñoz-Fernández M , María García-Merino Isabel , Consuegra Fernández Irene , Gómez Rico Coral , Gallego de la Fuente Jorge , Palau Concejo Paula , Portilla Joaquín , Merino Esperanza , Reus Sergio , Boix Vicente , Giner Livia , Gadea Carmen , Portilla Irene , Pampliega María , Díez Marcos , Carlos Rodríguez Juan , Sánchez-Payá José , Luis Gómez Juan , Hernández Jehovana , Remedios Alemán María , del Mar Alonso María , Inmaculada Hernández María , Díaz-Flores Felicitas , García Dácil , Pelazas Ricardo , López Lirola Ana , Sanz Moreno José , Arranz Caso Alberto , Hernández Gutiérrez Cristina , Novella Mena María , Rubio Rafael , Pulido Federico , Bisbal Otilia , Hernando Asunción , Domínguez Lourdes , Rial Crestelo David , Bermejo Laura , Santacreu Mireia , Antonio Iribarren José , Arrizabalaga Julio , José Aramburu María , Camino Xabier , Rodríguez-Arrondo Francisco , Ángel von Wichmann Miguel , Pascual Tomé Lidia , Ángel Goenaga Miguel , Jesús Bustinduy Ma , Azkune Harkaitz , Ibarguren Maialen , Lizardi Aitziber , Kortajarena Xabier , Gutiérrez Félix , Masiá Mar , Padilla Sergio , Navarro Andrés , Montolio Fernando , Robledano Catalina , Gregori Colomé Joan , Adsuar Araceli , Pascual Rafael , Fernández Marta , García Elena , Alberto García José , Barber Xavier , Berenguer Juan , Carlos López Bernaldo de Quirós Juan , Gutiérrez Isabel , Ramírez Margarita , Padilla Belén , Gijón Paloma , Aldamiz-Echevarría Teresa , Tejerina Francisco , José Parras Francisco , Balsalobre Pascual , Diez Cristina , Pérez Latorre Leire , Vidal Francesc , Peraire Joaquín , Viladés Consuelo , Veloso Sergio , Vargas Montserrat , López-Dupla Miguel , Olona Montserrat , Rull Anna , Rodríguez-Gallego Esther , Alba Verónica , Montero Alonso Marta , López Aldeguer José , Blanes Juliá Marino , Tasias Pitarch María , Castro Hernández Iván , Calabuig Muñoz Eva , Cuéllar Tovar Sandra , Salavert Lletí Miguel , Fernández Navarro Juan , Miguel Molina Jose , González-garcia Juan , Arnalich Francisco , Ramón Arribas José , Ignacio Bernardino de la Serna Jose , Miguel Castro Juan , Escosa Luis , Herranz Pedro , Hontañón Victor , García-Bujalance Silvia , García López-Hortelano Milagros , González-Baeza Alicia , Luz Martín-Carbonero Maria , Mayoral Mario , Jose Mellado Maria , Esteban Micán Rafael , Montejano Rocio , Luisa Montes María , Moreno Victoria , Pérez-Valero Ignacio , Rodés Berta , Sainz Talia , Sendagorta Elena , Stella Alcáriz Natalia , Valencia Eulalia , Ramón Blanco José , Antonio Oteo José , Ibarra Valvanera , Metola Luis , Sanz Mercedes , Pérez-Martínez Laura , Dalmau David , Jaén Angels , Sanmartí Montse , Cairó Mireia , Martinez-Lacasa Javier , Velli Pablo , Font Roser , Xercavins Mariona , Alonso Noemí , Repáraz Jesús , Gracia Ruiz de Alda María , Teresa de León Cano María , Pierola Ruiz de Galarreta Beatriz , de los Santos Ignacio , Sanz Sanz Jesús , Salas Aparicio Ana , Sarriá Cepeda Cristina , Garcia-Fraile Fraile Lucio , Martín Gayo Enrique , Moreno Santiago , Luis Casado José , Dronda Fernando , Moreno Ana , Jesús Pérez Elías María , Gómez Ayerbe Cristina , Gutiérrez Carolina , Madrid Nadia , del Campo Terrón Santos , Martí Paloma , Ansa Uxua , Serrano Sergio , Jesús Vivancos María , Bernal Enrique , Cano Alfredo , Alcaraz García Antonia , Bravo Urbieta Joaquín , Muñoz Ángeles , Jose Alcaraz Maria , del Carmen Villalba Maria , García Federico , Hernández José , Peña Alejandro , Muñoz Leopoldo , Casas Paz , Chueca Natalia , Vinuesa David , Martinez-Montes Clara , García Fernando , Guerrero-Beltran Carlos , Del Romero Jorge , Rodríguez Carmen , Puerta Teresa , Carlos Carrió Juan , Vera Mar , Ballesteros Juan , Ayerdi Oskar , Antela Antonio , Losada Elena , Aguilera Antonio , Riera Melchor , Peñaranda María , Leyes María , Angels Ribas Ma , A Campins Antoni , Vidal Carmen , Fanjul Francisco , Murillas Javier , Homar Francisco , Santos Jesús , Gómez Ayerbe Crisitina , Viciana Isabel , Palacios Rosario , María González Carmen , Viciana Pompeyo , Espinosa Nuria , Fernando López-Cortés Luis , Podzamczer Daniel , Ferrer Elena , Imaz Arkaitz , Tiraboschi Juan , Silva Ana , Saumoy María , Olalla Julián , del Arco Alfonso , de la torre Javier , Luis Prada José , María García de Lomas Guerrero José , Pérez Stachowski Javier , Amador Concepción , Juan Martínez Onofre , Jesús Vera Francisco , Martínez Lorena , García Josefina , Alcaraz Begoña , Jimeno Amaya , Castro Iglesias Angeles , Pernas Souto Berta , Mena de Cea Alvaro , Galera Carlos , Albendin Helena , Pérez Aurora , Iborra Asunción , Moreno Antonio , Angustias Merlos Maria , Vidal Asunción , Suárez-García Inés , Malmierca Eduardo , González-Ruano Patricia , Martín Rodrigo Dolores , Omar Mohamed-Balghata Mohamed , A Pineda Juan , Macías Juan , Thomson Miguel , Delgado Elena , Benito Sonia , Montero Vanessa
TITLE=Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions
JOURNAL=Frontiers in Microbiology
VOLUME=10
YEAR=2019
URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00370
DOI=10.3389/fmicb.2019.00370
ISSN=1664-302X
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.