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About the Authors:
E. Fabian Cardozo
Roles Data curation, Formal analysis, Methodology, Software, Visualization, Writing - original draft, Writing - review & editing
Affiliation: Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, United States of America
Adriana Andrade
Roles Data curation, Resources, Writing - review & editing
Affiliation: The Johns Hopkins University, Baltimore, MD, United States of America
ORCID http://orcid.org/0000-0002-6984-5920
John W. Mellors
Roles Data curation, Funding acquisition, Writing - review & editing
Affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
Daniel R. Kuritzkes
Roles Data curation, Funding acquisition, Writing - review & editing
Affiliation: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States of America
ORCID http://orcid.org/0000-0001-6196-5883
Alan S. Perelson
Roles Formal analysis, Funding acquisition, Writing - original draft, Writing - review & editing
Affiliation: Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, United States of America
ORCID http://orcid.org/0000-0002-2455-0002
Ruy M. Ribeiro
Roles Conceptualization, Formal analysis, Funding acquisition, Methodology, Supervision, Visualization, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliations Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, United States of America, Laboratório de Biomatemática, Faculdade de Medicina, Universidade de Lisboa. Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
ORCID http://orcid.org/0000-0002-3988-8241Abstract
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors. Our model explains the existence and quantifies the three phases of HIV-1 RNA decay in RAL-based regimens vs. the two phases observed in therapies without RAL. Our findings indicate that HIV-1 infection is mostly sustained by short-lived infected cells with fast integration and a short viral production period, and by long-lived infected cells with slow integration but an equally short viral production period. We propose that these cells represent activated...