Supervisors info:
Δημήτριος Παρασκευής, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Βασιλική-Αναστασία Σύψα, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Γκίκας Μαγιορκίνης, Λέκτορας, Ιατρική, ΕΚΠΑ
Summary:
Background: Our previous analysis on 6,632 HIV-1 sequences sampled in Spain revealed that B/G and B/F recombinant forms were among the HIV-1 non-B clades with the higher prevalence in Spain (1.54% and 1.48%, respectively). Our aim was to investigate the patterns of B/G and B/F dispersal across Spain and estimate the spatiotemporal characteristics of their largest regional epidemics, using molecular methods.
Materials and Methods: We studied 102 B/G and 98 B/F sequences, available in the PR/RT regions. Sequences were isolated from HIV-1 diagnosed patients during 2002-2014 from 10 autonomies of Spain. Patients' samples were merged from two datasets: a) CoRIS (2004-2013), and b) Eastern Andalusia Resistance Cohort (2000-2014). We analyzed phylogenetically sequences from our study population along with the most closely related sequences to them (HIV BLAST tool; B/G:N=317; B/F:N=210), using maximum likelihood method with bootstrap evaluation as implemented in RAxML v8.0.20 (GTR+G model). Local transmission networks (LTNs) were phylogenetic clusters including sequences from Spain at proportions >70%. Phylodynamic analysis was performed by using a Bayesian method as implemented in BEAST v1.8.0 (birth-death model).
Results: Navarre (B/G:7.4%; B/F:14.8%) and Basque Country (B/G:4.9%; B/F:4.9%) were the autonomies where B/G and B/F were more frequently found. Phylogenetic analysis revealed that 86.3% (N=88) of the B/G sequences from Spain found within 9 LTNs (CRF14_BG:N=40, 1 LTN; CRF20_BG:N=27, 4 LTNs; URF B/G:N=19, 3 LTNs; CRF24_BG:N=2, 1 LTN). The two largest B/G LTNs included 40 (39.2%; CRF14_BG) and 18 (17.6%; CRF20_BG) sequences. The 94.4% (N=17) of the sequences found within the CRF20_BG LTN were from individuals living in Madrid reported men having sex with men (MSM) as transmission risk group. Analysis revealed Cuba as the most possible source of CRF20_BG subepidemic. Analysis also revealed that 74.5% (N=73) of the B/F sequences from Spain formed 9 LTNs (CRF47_BF:N=32, 1 LTN; CRF12_BF:N=26, 3 LTNs; CRF40_BF:N=6, 1 LTN; CRF44_BF:N=3, 1 LTN; CRF17_BF:N=2; 1 LTN; CRF39_BF:N=2, 1 LTN; CRF42_BF:N=2, 1 LTN). The largest B/F LTN (CRF47_BF) consisted of 32 (32.7%) sequences, the majority of which had been isolated from heterosexuals (N=25, 78.1%) living in Andalusia (N=10, 31.3%), Navarre (N=8, 25%) and Basque Country (N=7, 21.9%). Molecular clock analysis estimated that the time of the most recent common ancestor (tMRCA) of the subepidemics was in 1991 (median estimate; 95%HPD:1985-1996) (CRF14_BG), in 2004 (95%HPD:2002-2005) (CRF20_BG) and in 2004 (95%HPD:2002-2005) (CRF47_BF). The birth-death skylines suggested a large increase in number of infections for the CRF47_BF and CRF20_BG, lasting between 2005 and 2011. For the CRF14_BG the largest increase in number of new infections occurred during 1996-2005.
Conclusions: Our study revealed that the B/G and B/F transmissions are due to regional dispersal at a considerable proportion in Spain. The hot spot for one of the largest B/G regional subepidemics (CRF20_BG) in Spain was in Madrid, associated with MSM risk group and probably originated from Cuba. The tMRCA and transmission dynamics of the three largest outbreaks were diverse. The most recent subepidemics (CRF47_BF, CRF20_BG) showed a rapid increase that lasted for approximately six years, whilst the CRF14_BG epidemic growth occurred over a longer time period.
Keywords:
Molecular epidemiology, Recombined forms, Phylogenetics, Phylodynamics
