Molecular Epidemiology of HIV in Canada

Abstract

With over 35 million people currently infected, the World Health Organization considers HIV a global pandemic. HIV is characterized by a high mutation rate, which allows it to evade the host immune system and develop resistance to drugs. However, this extraordinary adaptive ability may also be the key to HIV’s demise. Through the field of phylodynamics, the evolutionary behavior of the virus is being studied in an attempt to control the epidemic. In this thesis, three papers are presented in which we analyze sequences generated through the Canadian HIV Strain and Drug Resistance Surveillance program. In chapter 2 we validate a classifier which distinguishes between recent and established infections based on the proportion of mixed bases observed in population-based pol sequences. Our results will help identify recent infections and improve incidence calculations. In chapter 3, we investigate immune-induced patterns in HIV that are shared by patients of the same ethnicity. An understanding of the forces shaping HIV evolution is instrumental to the development of a vaccine relevant to the Canadian epidemic. In chapter 4, we present preliminary results of a historical reconstruction of HIV across the provinces of Canada. This analysis will highlight strategies that have succeeded or failed in controlling the epidemic. Furthermore, our work will establish whether non-B subtypes of HIV are an increasing threat to Canadian public health. Overall, this thesis provides the first country-wide evolutionary and phylogenetic analysis of the HIV epidemic.