Frontiers in Microbiology (Mar 2019)

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

  • 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

DOI
https://doi.org/10.3389/fmicb.2019.00370
Journal volume & issue
Vol. 10

Abstract

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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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