From Molecules to epidemics: Linking the within- and between-host evolution of HIV

Infection with chronic viruses, such as HIV and Hepatitis C, can lead to productive infections that last for decades. During this time the virus population is continuously adapting to the individual in which it finds itself, meaning the virus someone is infected with is unlikely to be the virus that they go on to transmit. I offer theoretical projects, using mathematical modelling approaches, focussed on understanding how adaptation within individuals impacts the evolution and epidemiology of these viruses at the population and continental scales. The project could take a number of different directions, for example:

1) The spread of transmitted drug resistance. When someone is diagnosed with HIV and put onto antiretroviral therapy, this therapy sometimes fails. This can either be because the virus evolves resistance during the course of the infection, usually due to interruptions of treatment, or because the initial (transmitted) infecting strain was resistant. Levels of transmitted drug resistance have remained low, at about 10%. However, in the coming decade it is expected that the number of people taking antiretrovirals to control disease, or to prevent infection, will increase dramatically, which could lead to large increases in levels of transmitted drug resistance. This project will tackle a number of related issues, such as the dynamics of the spread of drug resistance within individuals, how this is affected by treatment interruptions, the role of the viral reservoir on the within-host evolution of drug resistance (the reservoir ‘stores’ virus in an unchanging form over months and years), which strains are transmitted, and how this affects levels of transmitted drug resistance under different intervention strategies.

2) The evolution of virulence. For HIV, virulence is defined as the time it takes an infected individual to develop AIDS. Interestingly, HIV appears to have evolved a level of virulence that maximises its ability to transmit between individuals. This is despite hundreds, or even thousands, of rounds of replication within individuals, which should lead to the evolution of ever more virulent strains. Moreover, virulence seems to be increasing in some populations, but declining in others. Heterogeneity in the immune responses of individuals in a population, and among populations, might explain these patterns. The project will involve developing models of within host evolution of immune escape, explicitly incorporating the complicated within-host environment, and to nest these into epidemiological models where individuals differ in their immune status, with the ultimate aim of assessing the importance of host heterogeneity on the evolution of HIV virulence.