Identifying and monitoring HIV transmission networks can be important in understanding the evolutionary patterns and geospatial spread of the epidemic. Here, we reconstructed the broad molecular epidemiology of HIV in France from individuals enrolled at the time of primary HIV-1 infection (PHI) in the national ANRS PRIMO Cohort over 15 years.
Sociodemographic, geographic, clinical, and pol sequence data from 1356 cohort participants were collected between 1999 and 2014. Viruses mostly belonged to subtype B (71.5%) and CRF02_AG (15.3%). Network analysis was performed to infer genetic relationships, i.e. clusters, between HIV sequences. Bayesian coalescent-based methods were used to examine the temporal and spatial dynamics of identified clusters from different regions in France and the geographical patterns of viral spread and growth rate of HIV-1 subtype B and CRF02_AG subtypes.
Participants were mostly Caucasian (85.9%) and men (86.7%) who reported sex with other men (MSM, 71.9%). Overall, 387 individuals (29%) were involved in 78 dyads (n=156) and 231 participants fell in the remaining 42 clusters with 3 or more people (median size: 4, range 3-41). Compared to those who did not cluster (n=969), those in clusters with ≥3 people were more frequently men (98.3% vs 83%, p<0.01), MSM (88.3% vs 65.6%, p<0.01) and infected with CRF02_AG (27.3% vs 13.4%, p<0.01). Participants entering the cohort after 2011 (21.3%) clustered significantly more than participants entering before 2011 (20.6% in 2006-2010 and 10.1% before 2006, p<0.01). Phylogeographic analyses found a higher density of CRF02_AG clustering among participants residing in Paris versus those living outside Paris (p<0.01). Evolutionary analyses revealed that HIV-1 CRF02_AG epidemic arose more recently (time from the most common ancestor [TMRCA]=17.3 years, mean logistic growth rate [LGR]=0.051 year-1, mean evolutionary rate=4.91×10-3subs/site/year) and spread more rapidly among individuals with PHI in France than subtype B lineages (TMRCA=26.4 years, mean LGR=0.048 year-1, mean evolutionary rate=2.89×10-3subs/site/year).
These analyses support the hypothesis of a recent and rapid rise of CRF02_AG within the French HIV-1 epidemic among MSM. Since CRF02_AG is historically associated with various parts of Africa, such results may help us understand the relationships between migration of human populations and HIV-1 diffusion.