@article {20350,
	title = {Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions},
	journal = {Front MicrobiolFront MicrobiolFront Microbiol},
	volume = {10},
	year = {2019},
	note = {1664-302xKostaki, Evangelia-GeorgiaFlampouris, AndreasKaramitros, TimokratisChueca, NataliaAlvarez, MartaCasas, PazAlejos, BelenHatzakis, AngelosGarcia, FedericoParaskevis, DimitriosCoRISJournal ArticleFront Microbiol. 2019 Mar 11;10:370. doi: 10.3389/fmicb.2019.00370. eCollection 2019.},
	pages = {370},
	edition = {2019/03/28},
	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 (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.},
	keywords = {Crf02_ag, HIV-1, regional dispersal, Spain, spatiotemporal characteristics},
	isbn = {1664-302X (Print)1664-302x},
	author = {Kostaki, E. G. and Flampouris, A. and Karamitros, T. and Chueca, N and Alvarez, M and Casas, P. and Alejos, B. and Hatzakis, A and Garcia, F and Paraskevis, D}
}
