Background:  An understanding of HIV transmission dynamics is important in the design of effective prevention and treatment interventions. This study used a population-based phylogenetic approach to characterize transmission dynamics in Quebec.

Methods:  HIV-1 pol sequences from early stage infections (<6 months post-seroconversion, n = 593) were compiled from the Quebec Primary HIV Infection (PHI) cohort and the provincial genotyping program. Phylogenetic and maximum likelihood analyses were performed to determine sequence interrelationships among early stage infections. Transmission chains were identified by sequence clustering, ie, sequences having high bootstrap values (>98%) and genetic distances of >0.015% on trees. Comparative analysis was performed using a representative chronically infected potential transmitter population (n = 795). Since 70% of chronic infections harbored drug resistance, phylogenetic analysis was repeated after viral sequences were converted to wild type ancestral forms.

Results:  Viral sequences were obtained from early stage infections (~4.9 mean months post-seroconversion). Phylogenetic analysis showed that 24% of these infections co-segregated in small clusters involving 2.7±0.8 (mean ± SD) transmission events, while 25% of infections occurred within large clusters involving 8.8±3.5 transmission events. The remaining 51% of infections did not cluster. Phylogenetic analysis determined that chronic infections (35 of 795) rarely co-clustered with new infections. Our analysis revealed that 50%, 16%, and 12% of forward transmission events arise from persons in early, untreated chronic, and treated chronic stages of infection, respectively. Chronic infections that co-clustered with new ones included 16 wild type and 16 cases that harbored the M184V mutation but in which wild type ancestral forms were transmitted.

Conclusions:  Ours is a North American urban setting in which universal access to ART is available free. The majority of new infections arise from untreated persons at early stages of disease, underscoring the potential benefit of early treatment, as a means of preventing new infections.