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.
Highlights
Human immunodeficiency virus (HIV)-pandemic has been caused by Group M which is divided into nine subtypes (A, B, C, D, F, G, H, J, and K), six sub-subtypes (A1, A2, A3, A4, F1, F2) and an extensive list of at least 98 circulating recombinant forms (CRFs) which result from the recombination of two or more different subtypes (Foley et al, 2016
La Rioja (N = 11, 16.7%, 95% confidence interval (CI): 8.6–27.9%), Navarre (N = 11, 13.6%, 95% CI: 7–23%), Valencia (N = 22, 7.3%, 95% CI: 5.3–12.4%), and Andalusia (N = 240, 7%, 95% CI: 6.2– 8.0%) were the autonomous communities where CRF02_AG was most prevalent
Phylogenetic analysis revealed that the CRF02_AG sequences sampled from Spain clustered at different points in the Maximum-likelihood tree (Figure 1A)
Summary
Human immunodeficiency virus (HIV)-pandemic has been caused by Group M which is divided into nine subtypes (A, B, C, D, F, G, H, J, and K), six sub-subtypes (A1, A2, A3, A4, F1, F2) and an extensive list of at least 98 CRFs which result from the recombination of two or more different subtypes (Foley et al, 2016). The majority (46.6%) of the infections worldwide are caused by subtype C, followed by subtype B (12.1%) and subtype A (10.3%); the former is predominant in the Western world (Hemelaar et al, 2018). 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
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