Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion

Phan, Tin; Conway, Jessica M.; Pagane, Nicole; Kreig, Jasmine; Sambaturu, Narmada; Iyaniwura, Sarafa; Li, Jonathan Z.; Ribeiro, Ruy M.; Ke, Ruian; Perelson, Alan S.; Douek, ed., Daniel C.

doi:10.1371/journal.ppat.1012236

Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion

Journal Article · Mon Jul 29 00:00:00 EDT 2024 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1012236· OSTI ID:2427442

Phan, Tin; Conway, Jessica M.; Pagane, Nicole; Kreig, Jasmine; Sambaturu, Narmada; Iyaniwura, Sarafa; Li, Jonathan Z.; Ribeiro, Ruy M.; Ke, Ruian; ; Douek, ed., Daniel C.

Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.

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Research Organization:: Krell Institute, Ames, IA (United States); Triad National Security, LLC, Los Alamos, NM (United States)

Sponsoring Organization:: National Institute of Allergy and Infectious Diseases of the National Institutes of Health; National Institutes of Health (NIH); USDOE; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR)

Grant/Contract Number:: 89233218CNA000001; SC0022158

OSTI ID:: 2427442

Alternate ID(s):: OSTI ID: 2407168
OSTI ID: 2471931

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 7 Vol. 20; ISSN 1553-7374

Publisher:: Public Library of Science (PLoS)Copyright Statement

Country of Publication:: United States

Language:: English

References (94)

A flexible nonlinear mixed effects model for HIV viral load rebound after treatment interruption Wang, Rui; Bing, Ante; Wang, Cathy Statistics in Medicine, Vol. 39, Issue 15 https://doi.org/10.1002/sim.8529	journal	April 2020
HIV-1 Infection and Low Steady State Viral Loads Callaway, D. Bulletin of Mathematical Biology, Vol. 64, Issue 1 https://doi.org/10.1006/bulm.2001.0266	journal	January 2002
Towards a general function describing t cell proliferation De Boer, Rob J.; Perelson, A. S. Journal of Theoretical Biology, Vol. 175, Issue 4 https://doi.org/10.1006/jtbi.1995.0165	journal	August 1995
Modeling Plasma Virus Concentration during Primary HIV Infection Stafford, Max A.; Corey, Lawrence; Cao, Yunzhen Journal of Theoretical Biology, Vol. 203, Issue 3 https://doi.org/10.1006/jtbi.2000.1076	journal	April 2000
Practical Use of the Information-Theoretic Approach Burnham, Kenneth P.; Anderson, David R. Model Selection and Inference https://doi.org/10.1007/978-1-4757-2917-7_3	book	January 1998
A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population Chawla, Anita; Wang, Christina; Patton, Cody Infectious Diseases and Therapy, Vol. 7, Issue 2 https://doi.org/10.1007/s40121-018-0201-6	journal	May 2018
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis Ramratnam, Bharat; Bonhoeffer, Sebastian; Binley, James The Lancet, Vol. 354, Issue 9192 https://doi.org/10.1016/S0140-6736(99)02035-8	journal	November 1999
HIV-1 elite controllers: an immunovirological review and clinical perspectives Gebara, Nour Y.; El Kamari, Vanessa; Rizk, Nesrine Journal of Virus Eradication, Vol. 5, Issue 3 https://doi.org/10.1016/S2055-6640(20)30046-7	journal	July 2019
HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report Frange, Pierre; Faye, Albert; Avettand-Fenoël, Véronique The Lancet HIV, Vol. 3, Issue 1 https://doi.org/10.1016/S2352-3018(15)00232-5	journal	January 2016
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure Ho, Ya-Chi; Shan, Liang; Hosmane, Nina N. Cell, Vol. 155, Issue 3 https://doi.org/10.1016/j.cell.2013.09.020	journal	October 2013
HIV-1 Integration Landscape during Latent and Active Infection Cohn, Lillian B.; Silva, Israel T.; Oliveira, Thiago Y. Cell, Vol. 160, Issue 3 https://doi.org/10.1016/j.cell.2015.01.020	journal	January 2015
Dysfunctional HIV-Specific CD8+ T Cell Proliferation Is Associated with Increased Caspase-8 Activity and Mediated by Necroptosis Gaiha, Gaurav D.; McKim, Kevin J.; Woods, Matthew Immunity, Vol. 41, Issue 6 https://doi.org/10.1016/j.immuni.2014.12.011	journal	December 2014
Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point Ndhlovu, Zaza M.; Kamya, Philomena; Mewalal, Nikoshia Immunity, Vol. 43, Issue 3 https://doi.org/10.1016/j.immuni.2015.08.012	journal	September 2015
Prospective comparison of methicillin-susceptible and methicillin-resistant community-associated Staphylococcus aureus infections in hospitalized patients Skiest, Daniel J.; Brown, Katia; Cooper, Travis W. Journal of Infection, Vol. 54, Issue 5 https://doi.org/10.1016/j.jinf.2006.09.012	journal	May 2007
Modeling HIV persistence, the latent reservoir, and viral blips Rong, Libin; Perelson, Alan S. Journal of Theoretical Biology, Vol. 260, Issue 2 https://doi.org/10.1016/j.jtbi.2009.06.011	journal	September 2009
Asymmetric division of activated latently infected cells may explain the decay kinetics of the HIV-1 latent reservoir and intermittent viral blips Rong, Libin; Perelson, Alan S. Mathematical Biosciences, Vol. 217, Issue 1 https://doi.org/10.1016/j.mbs.2008.10.006	journal	January 2009
The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy Ramratnam, Bharat; Mittler, John E.; Zhang, Linqi Nature Medicine, Vol. 6, Issue 1 https://doi.org/10.1038/71577	journal	January 2000
Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy Finzi, Diana; Blankson, Joel; Siliciano, Janet D. Nature Medicine, Vol. 5, Issue 5 https://doi.org/10.1038/8394	journal	May 1999
HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors Migueles, Stephen A.; Laborico, Alisha C.; Shupert, W. Lesley Nature Immunology, Vol. 3, Issue 11 https://doi.org/10.1038/ni845	journal	October 2002
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation Chomont, Nicolas; El-Far, Mohamed; Ancuta, Petronela Nature Medicine, Vol. 15, Issue 8 https://doi.org/10.1038/nm.1972	journal	June 2009
Antiretroviral dynamics determines HIV evolution and predicts therapy outcome Rosenbloom, Daniel I. S.; Hill, Alison L.; Rabi, S. Alireza Nature Medicine, Vol. 18, Issue 9 https://doi.org/10.1038/nm.2892	journal	September 2012
Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells Siliciano, Janet D.; Kajdas, Joleen; Finzi, Diana Nature Medicine, Vol. 9, Issue 6 https://doi.org/10.1038/nm880	journal	May 2003
Molecular and cellular insights into T cell exhaustion Wherry, E. John; Kurachi, Makoto Nature Reviews Immunology, Vol. 15, Issue 8 https://doi.org/10.1038/nri3862	journal	July 2015
CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production Policicchio, Benjamin B.; Cardozo-Ojeda, Erwing Fabian; Xu, Cuiling Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-42435-8	journal	October 2023
Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells Passaes, Caroline; Desjardins, Delphine; Chapel, Anaïs Nature Communications, Vol. 15, Issue 1 https://doi.org/10.1038/s41467-023-44389-3	journal	January 2024
Defining ‘T cell exhaustion’ Blank, Christian U.; Haining, W. Nicholas; Held, Werner Nature Reviews Immunology, Vol. 19, Issue 11 https://doi.org/10.1038/s41577-019-0221-9	journal	September 2019
Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy Blazkova, Jana; Gao, Feng; Marichannegowda, Manukumar Honnayakanahalli Nature Medicine, Vol. 27, Issue 11 https://doi.org/10.1038/s41591-021-01503-6	journal	October 2021
Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1 Hill, Alison L.; Rosenbloom, Daniel I. S.; Fu, Feng Proceedings of the National Academy of Sciences, Vol. 111, Issue 37 https://doi.org/10.1073/pnas.1406663111	journal	August 2014
Post-treatment control of HIV infection Conway, Jessica M.; Perelson, Alan S. Proceedings of the National Academy of Sciences, Vol. 112, Issue 17 https://doi.org/10.1073/pnas.1419162112	journal	April 2015
Clonally expanded CD4 ⁺ T cells can produce infectious HIV-1 in vivo Simonetti, Francesco R.; Sobolewski, Michele D.; Fyne, Elizabeth Proceedings of the National Academy of Sciences, Vol. 113, Issue 7 https://doi.org/10.1073/pnas.1522675113	journal	February 2016
Regulation of T cell expansion by antigen presentation dynamics Mayer, Andreas; Zhang, Yaojun; Perelson, Alan S. Proceedings of the National Academy of Sciences, Vol. 116, Issue 13 https://doi.org/10.1073/pnas.1812800116	journal	March 2019
A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections Baral, Subhasish; Antia, Rustom; Dixit, Narendra M. Proceedings of the National Academy of Sciences, Vol. 116, Issue 35 https://doi.org/10.1073/pnas.1902178116	journal	August 2019
HIV post-treatment controllers have distinct immunological and virological features Etemad, Behzad; Sun, Xiaoming; Li, Yijia Proceedings of the National Academy of Sciences, Vol. 120, Issue 11 https://doi.org/10.1073/pnas.2218960120	journal	March 2023
Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy Chun, T. -W.; Stuyver, L.; Mizell, S. B. Proceedings of the National Academy of Sciences, Vol. 94, Issue 24 https://doi.org/10.1073/pnas.94.24.13193	journal	November 1997
HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression Davey, R. T.; Bhat, N.; Yoder, C. Proceedings of the National Academy of Sciences, Vol. 96, Issue 26 https://doi.org/10.1073/pnas.96.26.15109	journal	December 1999
Predictors of HIV Drug‐Resistance Mutations in a Large Antiretroviral‐Naive Cohort Initiating Triple Antiretroviral Therapy Harrigan, P. Richard; Hogg, Robert S.; Dong, Winnie W. Y. The Journal of Infectious Diseases, Vol. 191, Issue 3 https://doi.org/10.1086/427192	journal	February 2005
Evidence That Intermittent Structured Treatment Interruption, but Not Immunization with ALVAC‐HIV vCP1452, Promotes Host Control of HIV Replication: The Results of AIDS Clinical Trials Group 5068 Jacobson, Jeffrey M.; Pat Bucy, R.; Spritzler, John The Journal of Infectious Diseases, Vol. 194, Issue 5 https://doi.org/10.1086/506364	journal	September 2006
Viral Decay Dynamics in HIV‐Infected Patients Receiving Ritonavir‐Boosted Saquinavir and Efavirenz With or Without Enfuvirtide: A Randomized, Controlled Trial (HIV‐NAT 012) Boyd, Mark A.; Dixit, Narendra M.; Siangphoe, Umaporn The Journal of Infectious Diseases, Vol. 194, Issue 9 https://doi.org/10.1086/508291	journal	November 2006
A Randomized, Partially Blinded Phase 2 Trial of Antiretroviral Therapy, HIV‐Specific Immunizations, and Interleukin‐2 Cycles to Promote Efficient Control of Viral Replication (ACTG A5024) Kilby, J. Michael; Bucy, R. Pat; Mildvan, Donna The Journal of Infectious Diseases, Vol. 194, Issue 12 https://doi.org/10.1086/509508	journal	December 2006
AIDS Clinical Trials Group 5197: A Placebo‐Controlled Trial of Immunization of HIV‐1–Infected Persons with a Replication‐Deficient Adenovirus Type 5 Vaccine Expressing the HIV‐1 Core Protein Schooley, Robert T.; Spritzler, John; Wang, Hongying The Journal of Infectious Diseases, Vol. 202, Issue 5 https://doi.org/10.1086/655468	journal	September 2010
Time to Viral Rebound After Interruption of Modern Antiretroviral Therapies Li, Jonathan Z.; Aga, Evgenia; Bosch, Ronald J. Clinical Infectious Diseases, Vol. 74, Issue 5 https://doi.org/10.1093/cid/ciab541	journal	June 2021
Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies Crooks, Amanda M.; Bateson, Rosalie; Cope, Anna B. Journal of Infectious Diseases, Vol. 212, Issue 9 https://doi.org/10.1093/infdis/jiv218	journal	April 2015
The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies Namazi, Golnaz; Fajnzylber, Jesse M.; Aga, Evgenia The Journal of Infectious Diseases, Vol. 218, Issue 12 https://doi.org/10.1093/infdis/jiy479	journal	August 2018
Natural killer cells in HIV-1 infection and therapy Mikulak, Joanna; Oriolo, Ferdinando; Zaghi, Elisa AIDS, Vol. 31, Issue 17 https://doi.org/10.1097/QAD.0000000000001645	journal	November 2017
Antiretroviral medication adherence and the development of class-specific antiretroviral resistance Gardner, Edward M.; Burman, William J.; Steiner, John F. AIDS, Vol. 23, Issue 9 https://doi.org/10.1097/QAD.0b013e32832ba8ec	journal	June 2009
Antiretroviral therapy in acute and recent HIV infection: a prospective multicenter stratified trial of intentionally interrupted treatment Volberding, Paul; Demeter, Lisa; Bosch, Ronald J. AIDS, Vol. 23, Issue 15 https://doi.org/10.1097/QAD.0b013e32832eb285	journal	January 2009
Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication Chun, Tae-Wook; Justement, J. Shawn; Murray, Danielle AIDS, Vol. 24, Issue 18 https://doi.org/10.1097/QAD.0b013e328340a239	journal	January 2010
Unified model of short- and long-term HIV viral rebound for clinical trial planning Conway, Jessica M.; Meily, Paige; Li, Jonathan Z. Journal of The Royal Society Interface, Vol. 18, Issue 177 https://doi.org/10.1098/rsif.2020.1015	journal	April 2021
Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis Bofill, M.; Janossy, G.; Lee, C. A. Clinical and Experimental Immunology, Vol. 88, Issue 2 https://doi.org/10.1111/j.1365-2249.1992.tb03068.x	journal	June 2008
NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection Alter, G.; Altfeld, M. Journal of Internal Medicine, Vol. 265, Issue 1 https://doi.org/10.1111/j.1365-2796.2008.02045.x	journal	January 2009
Specific HIV integration sites are linked to clonal expansion and persistence of infected cells Maldarelli, F.; Wu, X.; Su, L. Science, Vol. 345, Issue 6193 https://doi.org/10.1126/science.1254194	journal	June 2014
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8⁺ Lymphocytes Schmitz, Jorn E.; Kuroda, Marcelo J.; Santra, Sampa Science, Vol. 283, Issue 5403, p. 857-860 https://doi.org/10.1126/science.283.5403.857	journal	February 1999
Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques Lim, So-Yon; Lee, Jina; Osuna, Christa E. Science, Vol. 383, Issue 6687 https://doi.org/10.1126/science.adf7966	journal	March 2024
Delayed differentiation of potent effector CD8 ⁺ T cells reducing viremia and reservoir seeding in acute HIV infection Takata, Hiroshi; Buranapraditkun, Supranee; Kessing, Cari Science Translational Medicine, Vol. 9, Issue 377 https://doi.org/10.1126/scitranslmed.aag1809	journal	February 2017
Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption Esmaeilzadeh, Elmira; Etemad, Behzad; Lavine, Christy L. Science Translational Medicine, Vol. 15, Issue 695 https://doi.org/10.1126/scitranslmed.abq4490	journal	May 2023
Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections Johnson, P. L. F.; Kochin, B. F.; McAfee, M. S. Journal of Virology, Vol. 85, Issue 11 https://doi.org/10.1128/JVI.00166-11	journal	March 2011
Differential Impact of In Vivo CD8 ⁺ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques Chowdhury, Ankita; Hayes, Timothy L.; Bosinger, Steven E. Journal of Virology, Vol. 89, Issue 17 https://doi.org/10.1128/JVI.00869-15	journal	June 2015
Defective Human Immunodeficiency Virus-Specific CD8+ T-Cell Polyfunctionality, Proliferation, and Cytotoxicity Are Not Restored by Antiretroviral Therapy Migueles, Stephen A.; Weeks, Kristin A.; Nou, Eric Journal of Virology, Vol. 83, Issue 22 https://doi.org/10.1128/JVI.01153-09	journal	September 2009
The Breadth of Expandable Memory CD8 ⁺ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin Journal of Virology, Vol. 89, Issue 21 https://doi.org/10.1128/JVI.01527-15	journal	November 2015
Emergence of Polyfunctional CD8+ T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral Therapy Rehr, Manuela; Cahenzli, Julia; Haas, Anna Journal of Virology, Vol. 82, Issue 7 https://doi.org/10.1128/JVI.02383-07	journal	January 2008
Analysis of Human Immunodeficiency Virus Type 1 Gene Expression in Latently Infected Resting CD4+ T Lymphocytes In Vivo Hermankova, Monika; Siliciano, Janet D.; Zhou, Yan Journal of Virology, Vol. 77, Issue 13 https://doi.org/10.1128/JVI.77.13.7383-7392.2003	journal	July 2003
A Novel Antiviral Intervention Results in More Accurate Assessment of Human Immunodeficiency Virus Type 1 Replication Dynamics and T-Cell Decay In Vivo Markowitz, M.; Louie, M.; Hurley, A. Journal of Virology, Vol. 77, Issue 8 https://doi.org/10.1128/JVI.77.8.5037-5038.2003	journal	April 2003
Kinetics of Virus-Specific CD8+ T Cells and the Control of Human Immunodeficiency Virus Infection Davenport, M. P.; Ribeiro, R. M.; Perelson, A. S. Journal of Virology, Vol. 78, Issue 18 https://doi.org/10.1128/JVI.78.18.10096-10103.2004	journal	August 2004
Human Immunodeficiency Virus: Quasi-Species and Drug Resistance Murray, John M.; Perelson, Alan S. Multiscale Modeling & Simulation, Vol. 3, Issue 2 https://doi.org/10.1137/040603024	journal	January 2005
HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers Sharaf, Radwa; Lee, Guinevere Q.; Sun, Xiaoming Journal of Clinical Investigation, Vol. 128, Issue 9 https://doi.org/10.1172/JCI120549	journal	August 2018
HLA-E–restricted HIV-1–specific CD8+ T cell responses in natural infection Bansal, Anju; Gehre, Mika N.; Qin, Kai Journal of Clinical Investigation, Vol. 131, Issue 16 https://doi.org/10.1172/JCI148979	journal	August 2021
The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy McMyn, Natalie F.; Varriale, Joseph; Fray, Emily J. Journal of Clinical Investigation, Vol. 133, Issue 17 https://doi.org/10.1172/JCI171554	journal	September 2023
Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study Sacktor, Ned; Skolasky, Richard L.; Seaberg, Eric Neurology, Vol. 86, Issue 4 https://doi.org/10.1212/WNL.0000000000002277	journal	January 2016
Effect of Adherence to HAART on Virologic Outcome and on the Selection of Resistance-Conferring Mutations in NNRTI- or PI-Treated Patients Maggiolo, Franco; Airoldi, Monica; Kleinloog, Hendrik Daniël HIV Clinical Trials, Vol. 8, Issue 5 https://doi.org/10.1310/hct0805-282	journal	October 2007
Viral and Latent Reservoir Persistence in HIV-1–Infected Patients on Therapy Kim, Hwijin; Perelson, Alan S. PLoS Computational Biology, Vol. 2, Issue 10 https://doi.org/10.1371/journal.pcbi.0020135	journal	January 2006
Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in HIV-infected Patients on Potent Therapy Rong, Libin; Perelson, Alan S. PLoS Computational Biology, Vol. 5, Issue 10 https://doi.org/10.1371/journal.pcbi.1000533	journal	October 2009
Treatment-Mediated Alterations in HIV Fitness Preserve CD4+ T Cell Counts but Have Minimal Effects on Viral Load Vaidya, Naveen K.; Rong, Libin; Marconi, Vincent C. PLoS Computational Biology, Vol. 6, Issue 11 https://doi.org/10.1371/journal.pcbi.1001012	journal	November 2010
A Stochastic Model of Latently Infected Cell Reactivation and Viral Blip Generation in Treated HIV Patients Conway, Jessica M.; Coombs, Daniel PLoS Computational Biology, Vol. 7, Issue 4 https://doi.org/10.1371/journal.pcbi.1002033	journal	April 2011
Residual Viremia in Treated HIV+ Individuals Conway, Jessica M.; Perelson, Alan S. PLOS Computational Biology, Vol. 12, Issue 1 https://doi.org/10.1371/journal.pcbi.1004677	journal	January 2016
Predictions of time to HIV viral rebound following ART suspension that incorporate personal biomarkers Conway, Jessica M.; Perelson, Alan S.; Li, Jonathan Z. PLOS Computational Biology, Vol. 15, Issue 7 https://doi.org/10.1371/journal.pcbi.1007229	journal	July 2019
Early exposure to broadly neutralizing antibodies may trigger a dynamical switch from progressive disease to lasting control of SHIV infection Desikan, Rajat; Raja, Rubesh; Dixit, Narendra M. PLOS Computational Biology, Vol. 16, Issue 8 https://doi.org/10.1371/journal.pcbi.1008064	journal	August 2020
Models of SIV rebound after treatment interruption that involve multiple reactivation events van Dorp, Christiaan H.; Conway, Jessica M.; Barouch, Dan H. PLOS Computational Biology, Vol. 16, Issue 10 https://doi.org/10.1371/journal.pcbi.1008241	journal	October 2020
Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy Wells, Chad R.; Cao, Youfang; Durham, David P. PLOS Computational Biology, Vol. 17, Issue 6 https://doi.org/10.1371/journal.pcbi.1009031	journal	June 2021
HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1 Altfeld, Marcus; Kalife, Elizabeth T.; Qi, Ying PLoS Medicine, Vol. 3, Issue 10 https://doi.org/10.1371/journal.pmed.0030403	journal	October 2006
CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells Klatt, Nichole R.; Shudo, Emi; Ortiz, Alex M. PLoS Pathogens, Vol. 6, Issue 1 https://doi.org/10.1371/journal.ppat.1000747	journal	January 2010
Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies Eriksson, Susanne; Graf, Erin H.; Dahl, Viktor PLoS Pathogens, Vol. 9, Issue 2 https://doi.org/10.1371/journal.ppat.1003174	journal	February 2013
Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study Sáez-Cirión, Asier; Bacchus, Charline; Hocqueloux, Laurent PLoS Pathogens, Vol. 9, Issue 3 https://doi.org/10.1371/journal.ppat.1003211	journal	March 2013
HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin PLOS Pathogens, Vol. 11, Issue 7 https://doi.org/10.1371/journal.ppat.1005000	journal	July 2015
Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV Hill, Alison L.; Rosenbloom, Daniel I. S.; Goldstein, Edward PLOS Pathogens, Vol. 12, Issue 4 https://doi.org/10.1371/journal.ppat.1005535	journal	April 2016
Modeling of Experimental Data Supports HIV Reactivation from Latency after Treatment Interruption on Average Once Every 5–8 Days Pinkevych, Mykola; Kent, Stephen J.; Tolstrup, Martin PLOS Pathogens, Vol. 12, Issue 8 https://doi.org/10.1371/journal.ppat.1005740	journal	August 2016
Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy Fennessey, Christine M.; Pinkevych, Mykola; Immonen, Taina T. PLOS Pathogens, Vol. 13, Issue 5 https://doi.org/10.1371/journal.ppat.1006359	journal	May 2017
CD8+ lymphocyte control of SIV infection during antiretroviral therapy Cao, Youfang; Cartwright, Emily K.; Silvestri, Guido PLOS Pathogens, Vol. 14, Issue 10 https://doi.org/10.1371/journal.ppat.1007350	journal	October 2018
Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication Pinkevych, Mykola; Docken, Steffen S.; Okoye, Afam A. PLOS Pathogens, Vol. 19, Issue 10 https://doi.org/10.1371/journal.ppat.1011660	journal	October 2023
CD8+ cells and small viral reservoirs facilitate post-ART control of SIV replication in M3+ Mauritian cynomolgus macaques initiated on ART two weeks post-infection Harwood, Olivia E.; Matschke, Lea M.; Moriarty, Ryan V. PLOS Pathogens, Vol. 19, Issue 9 https://doi.org/10.1371/journal.ppat.1011676	journal	September 2023
Learning From the Exceptions: HIV Remission in Post-treatment Controllers Etemad, Behzad; Esmaeilzadeh, Elmira; Li, Jonathan Z. Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01749	journal	July 2019
HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression? Bandera, Alessandra; Taramasso, Lucia; Bozzi, Giorgio Frontiers in Aging Neuroscience, Vol. 11 https://doi.org/10.3389/fnagi.2019.00187	journal	August 2019
Methamphetamine Induces the Release of Proadhesive Extracellular Vesicles and Promotes Syncytia Formation: A Potential Role in HIV-1 Neuropathogenesis Chand, Subhash; DeMarino, Catherine; Gowen, Austin Viruses, Vol. 14, Issue 3 https://doi.org/10.3390/v14030550	journal	March 2022
Interplay between Autophagy, Exosomes and HIV-1 Associated Neurological Disorders: New Insights for Diagnosis and Therapeutic Applications Ojha, Chet; Lapierre, Jessica; Rodriguez, Myosotys Viruses, Vol. 9, Issue 7 https://doi.org/10.3390/v9070176	journal	July 2017
Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation: Report of 2 Cases Henrich, Timothy J.; Hanhauser, Emily; Marty, Francisco M. Annals of Internal Medicine, Vol. 161, Issue 5 https://doi.org/10.7326/M14-1027	journal	September 2014

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Predictions of time to HIV viral rebound following ART suspension that incorporate personal biomarkers

Journal Article · Tue Jul 23 20:00:00 EDT 2019 · PLoS Computational Biology (Online) · OSTI ID:1627260

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Antiretroviral therapy
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Immune response
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Viral load
Viral replication
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Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion

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