OA Epidemiology

Requirements for Evolutionary Stability of Therapeutic Interfering Particles (TIPs) and HIV in High-Risk Populations

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

Background
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.

Methods
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.

Results
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.

Conclusions
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

 
Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)