Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society
Volume 1 Issue S1 Abstract 7
G. Rozhnova, Theoretical Physics Division, School of Physics and Astronomy, The University of Manchester
I. Rouzine, Gladstone Institutes, San Francisco, CA
L. Weinberger, Department of Biochemistry and Biophysics, University of California, San Francisco, CA
The fight against HIV remains complicated with the absence of a protective vaccine and the difficulty of delivering treatment to high-risk populations, who bear disproportionately high disease burdens. We investigate a therapy intervention based upon the concept of TIPs, designed to target these populations. TIPs are HIV mutants engineered to replicate at the expense of the wild-type virus and transmit between individuals via the same routes as HIV.
Using a mathematical model that integrates HIV-TIP dynamics at three biological scales --- a host population, an individual host and a single cell --- we determine the molecular characteristics of TIPs and HIV necessary for an effective reduction of HIV disease prevalence by TIP intervention.
The threshold at which TIPs become stable in a population approaches TIP stability threshold in a host if HIV prevalence before TIP introduction exceeds 50-60%. In this case, we predict a
7-fold reduction in prevalence within 25 years. We further investigate whether HIV can escape interference from TIP by changing genetically. The problem is reduced to knowing the direction of HIV evolution in a host: if HIV evolves towards a parameter region permissive to stable TIP introduction, the evolutionary co-stability of TIPs and HIV is predicted in a population as well. The actual direction of HIV evolution depends on the molecular mechanism of HIV-TIP interference.
For the recently described "capsid-stealing" model of interference, we demonstrate that TIP intervention is robust to HIV evolution, in contrast to current treatment programs frequently leading to drug resistance.
Published: 06 Jun, 2013