Abstract
Infectious disease treatments, both pharmaceutical and vaccine, face
three universal challenges: the difficulty of targeting treatments to
high-risk `superspreader' populations who drive the great majority of
disease spread, behavioral barriers in the host population (such as poor
compliance and risk disinhibition), and the evolution of pathogen
resistance. Here, we describe a proposed intervention that would
overcome these challenges by capitalizing upon Therapeutic Interfering
Particles (TIPs) that are engineered to replicate conditionally in the
presence of the pathogen and spread between individuals - analogous to
`transmissible immunization' that occurs with live-attenuated vaccines
(but without the potential for reversion to virulence). Building on
analyses of HIV field data from sub-Saharan Africa, we construct a
multiscale model, beginning at the single-cell level, to predict the
effect of TIPs on individual patient viral loads and ultimately
population-level disease prevalence. Our results show that a TIP,
engineered with properties based on a recent HIV gene-therapy trial,
could stably lower HIV/AIDS prevalence by, similar to 30-fold within 50
years and could complement current therapies. In contrast, optimistic
antiretroviral therapy or vaccination campaigns alone could only lower
HIV/AIDS prevalence by, <2-fold over 50 years. The TIP's efficacy arises
from its exploitation of the same risk factors as the pathogen, allowing
it to autonomously penetrate superspreader populations, maintain
efficacy despite behavioral disinhibition, and limit viral resistance.
While demonstrated here for HIV, the TIP concept could apply broadly to
many viral infectious diseases and would represent a new paradigm for
disease control, away from pathogen eradication but toward robust
disease suppression.
