Work

Real-time predictions of reservoir size and rebound time during antiretroviral therapy interruption trials for HIV

Year: 2015

Type: article

Abstract: Background: Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging.The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required.Methods: We introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials.These tools combine previously developed models of reservoir dynamics and rebound with patient-derived data in a flexible Bayesian framework.Results: We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from dynamic models.We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound.While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used.We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays.Our findings suggest that large numbers of patients -between 40 and 150 -will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions.As an example, we apply these methods to the two "Boston patients".Conclusions: These tools can aid researchers in evaluating new potentially-curative strategies that target the latent reservoir. OP 8.2The importance of GPP implementation in HIV cure research: learning from prevention

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)31327-3

Authors: A.L. Hill, D.I.S. Rosenbloom, D.R. Kuritzkes, R.F. Siliciano, T.J. Henrich