Methods: Using a mathematical model of HIV dynamics, we explored the possible role of drug sanctuaries and proliferation of latent cells in HIV persistence. Our model uses published estimates of the three phases of viral decay on ART to define three infected cell states: productive infection, pre-integration latency, and post-integration latency and measures the degree of viral diversity expected as a function of time on ART.
Results: Our model predicts that the percentage of latently infected cells born of new infection, rather than proliferation, decreases dramatically as time on ART increases. Conversely, the percentage arising from proliferation increases over time on ART. While we are able to reproduce realistic viral load data with a model that includes a drug sanctuary during the early months of ART, its importance in sustaining chronic HIV infection diminishes over time due to decreased activation of CD4+ T cells on ART.
Conclusion: Given that drug sanctuaries—and thus, ongoing viral evolution—do not sustain chronic HIV infection on ART, enhancing ART delivery to drug sanctuary sites would not decrease the HIV reservoir and cure HIV. Rather, eradication strategies should strive to eliminate existing reservoir cells.
A. Spivak, None
J. Schiffer, None