RT Journal Article SR Electronic T1 A compound interest approach to HIV cure JF bioRxiv FD Cold Spring Harbor Laboratory SP 063305 DO 10.1101/063305 A1 Daniel B Reeves A1 Elizabeth R Duke A1 Martin Prlic A1 Florian Hladik A1 Joshua T Schiffer YR 2016 UL http://biorxiv.org/content/early/2016/07/12/063305.abstract AB In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of integrated virus to persist within memory CD4+T cells in a transcriptionally quiescent state and reactivate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART would result in functional cure within 2-10 years rather than many decades on ART alone.