Molecular epidemiology can be used to identify large recent transmission clusters (RTC) and describe core transmitters that fuel a large proportion of transmissions. We analyzed such RTC among primary infected patients (PHI) diagnosed in France in 2014-2016.
Protease and reverse transcriptase sequences were obtained from 1121 patients included between 2014 and 2016 from 46 centers. Phylogenetic trees were built by approximate maximum likelihood using FastTree to identify RTC (max genetic distance <4.5%, branch support value >95%).
Most patients were men (90%), MSM (70%), born in France (70%) or Sub-Saharan Africa (6.6%), infected mostly by B (56%) or CRF02_AG (20%) clades. CRF02_AG tended to be increasingly represented across years (from 17 to 22%) and large (>3 patients) RTC (Table). Compared to patients infected by subtype B, patients infected by CRF02_AG presented a lower proportion of MSM (59 vs 78%, p<0.001), of individual born in France (67 vs 75%, p=0.02), higher viral loads (VL) (median at 5.83 log10 copies/mL [IQR: 4.96-6.60] vs 5.40 [4.66-6.26], p=0.004) and lower CD4 cell counts (463 cells/mm3 [25-903] vs 514 [1-1028], p=0.004). When analyzing patients born in France separately, CRF02_AG still presented higher VL than subtype B (5.79 vs 5.42 log10 copies/mL, p=0.012). Overall, 457 (41%) patients were included in RTC including 214 (47%) in 106 small (<4 patients) and 243 (53%) patients in 39 large RTC (from 4 to 14 patients). Paris area appeared as a hub for transmission with 31/39 large RTC including ≥1 patient from this area. RTC-patients were younger and more frequently MSM than non-RTC-patients (p<0.001). Most large RTC sustained active transmissions over the whole study period. Four large clusters were identified with transmitted drug resistance mutation(s) (T215S, L74M, K103N and L76V+L90M) but none achieved sustainable transmission of these mutations throughout their cluster.
This study highlights the important role of RTC achieving transmission throughout France with a large hub in Paris area. CRF02_AG is actively spreading among large RTC, participating to the epidemiological shift from B to CRF02_AG in France. CRF02_AG is also associated to higher VL among patients born in France, suggesting a higher virulence than subtype B. The increasing number of large RTC identified highlights the need for nationwide surveillance and intervention programs to identify and fight these, sometimes massive, local outbreaks.