Grant: CIHR Fellowship

Antiretroviral therapy (ART) represents a major leap forward in HIV treatment, but it is not a cure. As long as a patient takes their medication the virus is forced into hiding in cells, but it can reappear from these hiding places when ART is stopped. Therefore, a cure to treat those individuals who are already HIV-positive is desperately required, as is a vaccine to limit the spread of this virus. The major HIV-infected (HIV+) cell, a type of white blood cell known as CD4 T cells, comes in multiple different "flavours", each with different functions. Scientists need to understand which flavours of CD4 T cells are infected in order to develop both a cure that can clear HIV from its hiding places, and a protective vaccine that can teach the immune system how to target and kill HIV+ cells. However, current technologies have made it difficult to visualize the flavours of these HIV+ cells in great detail. Previous work has looked at the relative numbers of HIV+ cells in different populations, rather than the individual HIV+ cells, or has studied HIV infection using cells and viruses grown in the lab. The interactions between these "in vitro" cells and viruses may be very different to the events occurring within a HIV-positive individual. To address this important issue, we have developed a novel assay that, for the first time, allows very rare, HIV+ cells to be visualized at a single-cell level. We will perform in-depth analysis of individual HIV+ cells from the blood and tissues of HIV-positive individuals. This will provide researchers with a highly detailed picture of HIV+ cells and guide development of a vaccine. Specialized drugs (known as latency reversing agents or LRAs) have been developed to try to kick the virus out of its hiding places and so cure HIV; however, the effectiveness of these drugs is unknown. We will investigate how different flavours of CD4 T cells respond to LRAs, and use this knowledge to inform studies working towards a cure for HIV.