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This work was supported by Plan Nacional de I + D + I and Fondo Europeo de Desarrollo Regional-FEDER (RD16/0025/0040 and PI18/00819) and Fundacion Progreso y Salud, Junta de Andalucia (PI-0550-2017). The study was in part funded by the Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases.

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

Publicat a:Frontiers In Microbiology. 10 370- - 2019-03-11 10(), DOI: 10.3389/fmicb.2019.00370

Autors: Kostaki, Evangelia-Georgia; Flampouris, Andreas; Karamitros, Timokratis; Chueca, Natalia; Alvarez, Marta; Casas, Paz; Alejos, Belen; Hatzakis, Angelos; Garcia, Federico; Paraskevis, Dimitrios; Moreno, Santiago; Dalmau, David; Rubio, Rafael; Gutierrez, Felix; Vidal, Francesc; Berenguer, Juan; Angeles Munoz-Fernandez, M; Maria Garcia-Merino, Isabel; Consuegra Fernandez, Irene; Gomez Rico, Coral; Gallego de la Fuente, Jorge; Palau Concejo, Paula; Portilla, Joaquin; Merino, Esperanza; Reus, Sergio; Boix, Vicente; Giner, Livia; Gadea, Carmen; Portilla, Irene; Pampliega, Maria; Diez, Marcos; Carlos Rodriguez, Juan; Sanchez-Paya, Jose; Luis Gomez, Juan; Hernandez, Jehovana; Remedios Aleman, Maria; del Mar Alonso, Maria; Inmaculada Hernandez, Maria; Diaz-Flores, Felicitas; Garcia, Dacil; Pelazas, Ricardo; Lopez Lirola, Ana; Sanz Moreno, Jose; Arranz Caso, Alberto; Hernandez Gutierrez, Cristina; Novella Mena, Maria; Pulido, Federico; Bisbal, Otilia; Hernando, Asuncion; Dominguez, Lourdes; Rial Crestelo, David; Bermejo, Laura; Santacreu, Mireia; Antonio Iribarrena, Jose; Arrizabalaga, Julio; Jose Aramburu, Maria; Camino, Xabier; Rodriguez-Arrondo, Francisco; Angel von Wichmann, Miguel; Pascual Tome, Lidia; Angel Goenaga, Miguel; Jesus Bustinduy, Ma; Azkune, Harkaitz; Ibarguren, Maialen; Lizardi, Aitziber; Kortajarena, Xabier; Masia, Mar; Padilla, Sergio; Navarro, Andres; Montolio, Fernando; Robledano, Catalina; Gregori Colome, Joan; Adsuar, Araceli; Pascual, Rafael; Fernandez, Marta; Garcia, Elena; Alberto Garcia, Jose; Barber, Xavier; Bernaldo de Quiros, Juan Carlos Lopez; Gutierrez, Isabel; Ramirez, Margarita; Padilla, Belen; Gijon, Paloma; Aldamiz-Echevarria, Teresa; Tejerina, Francisco; Jose Parras, Francisco; Balsalobre, Pascual; Diez, Cristina; Perez Latorre, Leire; Peraire, Joaquin; Vilades, Consuelo; Veloso, Sergio; Vargas, Montserrat; Lopez-Dupla, Miguel; Olona, Montserrat; Rull, Anna; Rodriguez-Gallego, Esther; Alba, Veronica; Montero Alonso, Marta; Lopez Aldeguer, Jose; Blanes Julia, Marino; Tasias Pitarch, Maria; Castro Hernandez, Ivan; Calabuig Munoz, Eva; Cuellar Tovar, Sandra; Salavert Lleti, Miguel; Fernandez Navarro, Juan; Miguel Molina, Jose; Gonzalez-garcia, Juan; Arnalich, Francisco; Ramon Arribas, Jose; Bernardino de la Serna, Jose Ignacio; Miguel Castro, Juan; Escosa, Luis; Herranz, Pedro; Hontanon, Victor; Garcia-Bujalance, Silvia; Garcia Lopez-Hortelano, Milagros; Gonzalez-Baeza, Alicia; Luz Martin-Carbonero, Maria; Mayoral, Mario; Jose Mellado, Maria; Esteban Mican, Rafael; Montejano, Rocio; Luisa Montes, Maria; Moreno, Victoria; Perez-Valero, Ignacio; Rodes, Berta; Sainz, Talia; Sendagorta, Elena; Stella Alcariz, Natalia; Valencia, Eulalia; Ramon Blanco, Jose; Antonio Oteo, Jose; Ibarra, Valvanera; Metola, Luis; Sanz, Mercedes; Perez-Martinez, Laura; Jaen, Angels; Sanmarti, Montse; Cairo, Mireia; Martinez-Lacasa, Javier; Velli, Pablo; Font, Roser; Xercavins, Mariona; Alonso, Noemi; Rivero, Maria; Reparaz, Jesus; Ruiz de Alda, Maria Gracia; de Leon Cano, Maria Teresa; Ruiz de Galarreta, Beatriz Pierola; de los Santos, Ignacio; Sanz Sanz, Jesus; Salas Aparicio, Ana; Sarria Cepeda, Cristina; Garcia-Fraile Fraile, Lucio; Martin Gayo, Enrique; Luis Casado, Jose; Dronda, Fernando; Moreno, Ana; Perez Elias, Maria Jesus; Gomez Ayerbe, Cristina; Gutierrez, Carolina; Madrid, Nadia; del Campo Terron, Santos; Marti, Paloma; Ansa, Uxua; Serrano, Sergio; Jesus Vivancos, Maria; Bernal, Enrique; Cano, Alfredo; Alcaraz Garcia, Antonia; Bravo Urbieta, Joaquin; Munoz, Angeles; Jose Alcaraz, Maria; del Carmen Villalba, Maria; Garciaa, Federico; Hernandez, Jose; Pena, Alejandro; Munoz, Leopoldo; Vinuesa, David; Martinez-Montes, Clara; Garcia, Fernando; Guerrero-Beltran, Carlos; Del Romero, Jorge; Rodriguez, Carmen; Puerta, Teresa; Carlos Carrio, Juan; Vera, Mar; Ballesteros, Juan; Ayerdi, Oskar; Antela, Antonio; Losada, Elena; Aguilera, Antonio; Riera, Melchor; Penaranda, Maria; Leyes, Maria; Angels Ribas, Ma; Campins, Antoni A; Vidal, Carmen; Fanjul, Francisco; Murillas, Javier; Homar, Francisco; Santos, Jesus; Gomez Ayerbe, Crisitina; Viciana, Isabel; Palacios, Rosario; Maria Gonzalez, Carmen; Viciana, Pompeyo; Espinosa, Nuria; Fernando Lopez-Cortes, Luis; Podzamczer, Daniel; Ferrer, Elena; Imaz, Arkaitz; Tiraboschi, Juan; Silva, Ana; Saumoy, Maria; Olalla, Julian; del Arco, Alfonso; de la Torre, Javier; Luis Prada, Jose; de Lomas Guerrero, Jose Maria Garcia; Perez Stachowski, Javier; Amador, Concepcion; Juan Martinez, Onofre; Jesus Vera, Francisco; Martinez, Lorena; Garcia, Josefina; Alcaraz, Begona; Jimeno, Amaya; Castro Iglesias, Angeles; Pernas Souto, Berta; Mena de Cea, Alvaro; Galera, Carlos; Albendin, Helena; Perez, Aurora; Iborra, Asuncion; Moreno, Antonio; Angustias Merlos, Maria; Vidal, Asuncion; Suarez-Garcia, Ines; Malmierca, Eduardo; Gonzalez-Ruano, Patricia; Martin Rodrigo, Dolores; Omar Mohamed-Balghata, Mohamed; Gomez Vidal, Maria Amparo; Pineda, Juan A; Macias, Juan; Bernal, Samuel; Thomson, Miguel; Delgado, Elena; Benito, Sonia; Montero, Vanessa

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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 279 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 (t(MRCA)) 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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