Time-measured phylogenies of gag, pol and env sequence data reveal the direction and time interval of HIV-1 transmission.

OBJECTIVE: To investigate whether time-measured phylogenetic analysis of longitudinal viral sequences can establish the direction and timing of HIV-1 transmission in an epidemiologically linked transmission cluster of three homosexual men.
DESIGN: An HIV-1-infected homosexual man (patient 1) and his long-term HIV-negative partner (patient 2) engaged in a triangular relationship with an additional partner (patient 3). On the basis of phylogenetic analysis of gag sequences, patient 3 was previously identified as the source for superinfection of patient 1 but the source of HIV-1 infection of patient 2, who seroconverted during the triangular relationship, remained unclear. Here, we set out to analyze newly obtained gag, pol and env sequences from all three patients to fully elucidate the transmission history in this epidemiologically linked cluster.
METHODS: Bayesian Markov Chain Monte Carlo (MCMC) phylogenetic analyses incorporating a relaxed clock model and a flexible Bayesian skyride tree prior were applied to the longitudinally obtained gag, pol and env sequences from all three patients.
RESULTS: Our time-measured evolutionary reconstructions convincingly supported transmission of HIV-1 from the new partner patient 3 to both patients 1 and 2. In addition, estimates of viral divergence times assisted in narrowing down the transmission intervals delineated by seroconversion estimates.
CONCLUSION: Our analysis implies that Bayesian MCMC phylogenetic reconstruction incorporating temporal information can indeed reveal the direction of multiple HIV-1 transmission events in an epidemiologically linked cluster and provide more detail on the timing of transmission.