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Unified model of short- and long-term HIV viral rebound for clinical trial planning

Journal Article · · Interface (Online)
 [1];  [2];  [3];  [4]
  1. Pennsylvania State Univ., University Park, PA (United States)
  2. Univ. of Pennsylvania, Philadelphia, PA (United States)
  3. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
+ Show Author Affiliations
Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Typically suspension of therapy is rapidly followed by rebound of viral loads to high, pre-therapy levels. Indeed, a recent study showed that approximately 90% of treatment interruption study participants show viral rebound within at most a few months of therapy suspension, but the remaining 10%, showed viral rebound some months, or years, after ART suspension. Some may even never rebound. We investigate and compare branching process models aimed at gaining insight into these viral dynamics. Specifically, we provide a theory that explains both short- and long-term viral rebounds, and post-treatment control, via a multitype branching process with time-inhomogeneous rates, validated with data from Li et al. We discuss the associated biological interpretation and implications of our best-fit model. To test the effectiveness of an experimental intervention in delaying or preventing rebound, the standard practice is to suspend therapy and monitor the study participants for rebound. We close with a discussion of an important application of our modelling in the design of such clinical trials.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE
Grant/Contract Number:
89233218CNA000001
OSTI ID:
1804378
Report Number(s):
LA-UR--21-22582
Journal Information:
Interface (Online), Journal Name: Interface (Online) Journal Issue: 177 Vol. 18; ISSN 1742-5662
Publisher:
The Royal SocietyCopyright Statement
Country of Publication:
United States
Language:
English

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60 APPLIED LIFE SCIENCES
HIV
latency
mathematical modeling
viral rebound