Grant: Doctoral Research Award - Priority Announcement - HIV/AIDS and/or STBBI

Human immunodeficiency virus or HIV, the cause of acquired immune deficiency syndrome or AIDS, continues to contribute to a widespread epidemic in Canada and the world. Although HIV infection can be managed during the full normal lifespan of infected individuals with combination antiretroviral therapies, these therapies cannot cure HIV infection because of the presence of "latent" HIV integrated into the individual's cells that the drugs cannot target. Elimination of each copy of HIV in an individual is necessary for HIV cure, since latent HIV in the latent reservoir can "wake up" at any time to restart the infection. However, there are many gaps in the understanding of latent HIV; it is currently contested whether the latent reservoir is continuously added to throughout the course of infection or whether reservoir contribution is concentrated to a specific period of infection and whether HIV is truly latent on therapy or if there are low levels of replication is still unclear. HIV's fast mutation rate and short life cycle "stamp" the viruses with measurable signatures of evolution. I plan to exploit the virus' evolutionary patterns by developing methods to learn from the virus including: a computer simulation of the latent reservoir, a phylogenetic dating technique that uses the evolutionary relationships of the viruses to infer when the viruses entered the reservoir and an advanced statistical (Bayesian) method that models the migration of HIV throughout the body. With these methods I will glean information on the timing of HIV integration into the latent reservoir, locations and pathways used by latent HIV and whether or not there is ongoing replication in the presence of therapy. Since every copy of HIV must be eliminated to cure HIV including in the latent reservoir, it is important to accurately understand the dynamics of the reservoir. A cure for HIV will eliminate transmission of HIV from cured individuals and will be a significant asset to end the pandemic.