HIV evolution of resistance

From EESwiki

Non adherence and the evolution of drug resistance

This is the short description of what I (Pleuni Pennings) plan to do in the next two years (summer 2010 - summer 2012) in the lab of John Wakeley at Harvard.

Drug resistance is a major problem in diseases such as cancer, malaria and HIV and despite strategies to avoid resistance (such as combination therapy) resistance still occurs and many questions remain. One question is why non-adherence (when a patient doesn't takes his drugs as prescribed) sometimes increases and sometimes decreases the risk of evolution of resistance. In principle, non-adherence can both slow down the evolution of resistance, because selection pressure decreases, or it can speed up the evolution of resistance, because the evolving population (e.g., the virus population) will grow, leading to more genetic variation on which selection can act. Whether the net result of non-adherence is slower or faster evolution must therefore depend on factors such as drug or virus characteristics, but it is not yet understood how. HIV is an ideal model to study the effect of the level of adherence on the evolution of drug resistance for two reasons: 1) because a patient usually gets infected with HIV once a and patients stay infected for life. An HIV strain therefore evolves within a patient for many years, independently from HIV strains in other patients. Every patient therefore represents an independent evolutionary history of a viral population. 2) The second reason for studying HIV is that there are good data available on patient adherence, on drug characteristics, and resistance mutations. I will combine stochastic modeling approaches and data-analysis to reach a better understanding of adherence-resistance relationships. The results will allow for design of better treatment strategies.