| My work with Human Immunodeficiency Virus 1 (HIV) has been directed primarily in two areas. The first is with the study of aspects of HIV persistence. HIV combination therapy has had a major impact on disease outcome in the developed world. However, even though these therapies can suppress virus in the blood below the limits of detection by current methods, the virus is far from eradicated in these hosts. HIV can either continue to replicate in cells that are not protected by therapy or the virus can evade the effects of therapy through viral latency. I have developed techniques that tease these two viral persistence mechanisms apart with the goal of informing next generation HIV therapies that might target these mechanisms.; The second area of focus of my work is on the development of an effective HIV vaccine. A primary obstacle in the development of a vaccine to combat the HIV pandemic can easily be couched in terms of molecular diversity. By analogy, one can imagine that vaccinologists are attempting to generate a predator (i.e., the immune system) to consume all mammals from the smallest kangaroos to the largest blue whales. The genetic diversity within HIV-1 is greater than that found in the fastest evolving mammalian mitochondrial genes. However, it is likely that not all the variation observed across HIV-infected patients is of importance, and therefore, not all of it needs to be accounted for when designing an HIV vaccine. The goal of my work is to define the most important features of the HIV's proteome that will maximize the level of cross-reactivity. I employ molecular evolutionary and population genetic theory to describe series of new and novel methods to generate vaccine candidates. |
