Population-based sequencing of primary/recent HIV infections (PHI) can provide a framework for understanding transmission dynamics of local epidemics. In Quebec, half of PHI represent clustered transmission events. This study ascertained the cumulative implications of clustering on onward transmission of drug resistance.
HIV-1 pol sequence datasets were available for all genotyped PHI (<6 months post-seroconversion (n=848 subtype B infections, 1997-2007). Phylogenetic analysis established clustered transmission events, based on maximum likelihood topologies having high bootstrap values (>98%) and short genetic distances. The distributions of resistance to nucleoside and non-nucleoside RT inhibitors (NRTIs and NNRTIs) and protease inhibitors (PIs) in unique and clustered transmissions were ascertained.
Episodic clustering was observed in half of recent/early stage infections from 1997-2008. Overall, 29% and 28% of new infections segregated into small (<5 PHI/cluster, n=242/848) and large transmission chains (≥5 PHI/cluster, n=239/848), averaging 2.8 ± 0.1 PHI/cluster and 10.3 ± 1.0 PHI/cluster, respectively. The transmission of nucleoside analogue mutations and 215 resistant variants (T215C/D/I/F/N/S/Y) declined with clustering (7.9% vs. 3.4% vs. 1.2% and 5.8% vs. 1.7% vs. 1.1% for unique, small and large clustered transmissions, respectively). In contrast, clustering was associated with the increased transmission of viruses harbouring resistance to NNRTIs (6.6% vs. 6.0% vs. 15.5%, respectively).
Clustering in early/PHI stage infection differentially affects transmission of drug resistance to different drug classes. Public health, prevention and diagnostic strategies, targeting PHI, afford a unique opportunity to curb the spread of transmitted drug resistance.