Residual Viremia in Treated HIV+ Individuals
Abstract
Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. Furthermore, the source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Our observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. The phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted,more »
- Authors:
-
- Pennsylvania State Univ., University Park, PA (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1236042
- Report Number(s):
- LA-UR-15-27439
Journal ID: ISSN 1553-7358
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Computational Biology (Online)
- Additional Journal Information:
- Journal Name: PLoS Computational Biology (Online); Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1553-7358
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; viral replication; viral load; cell activation; viremia; antiretroviral therapy; HIV; viral evolution; HIV infection
Citation Formats
Conway, Jessica M., and Perelson, Alan S. Residual Viremia in Treated HIV+ Individuals. United States: N. p., 2016.
Web. doi:10.1371/journal.pcbi.1004677.
Conway, Jessica M., & Perelson, Alan S. Residual Viremia in Treated HIV+ Individuals. United States. https://doi.org/10.1371/journal.pcbi.1004677
Conway, Jessica M., and Perelson, Alan S. Wed .
"Residual Viremia in Treated HIV+ Individuals". United States. https://doi.org/10.1371/journal.pcbi.1004677. https://www.osti.gov/servlets/purl/1236042.
@article{osti_1236042,
title = {Residual Viremia in Treated HIV+ Individuals},
author = {Conway, Jessica M. and Perelson, Alan S.},
abstractNote = {Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. Furthermore, the source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Our observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. The phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy.},
doi = {10.1371/journal.pcbi.1004677},
journal = {PLoS Computational Biology (Online)},
number = 1,
volume = 12,
place = {United States},
year = {Wed Jan 06 00:00:00 EST 2016},
month = {Wed Jan 06 00:00:00 EST 2016}
}
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Works referenced in this record:
HIV-1 Integration Landscape during Latent and Active Infection
journal, January 2015
- Cohn, Lillian B.; Silva, Israel T.; Oliveira, Thiago Y.
- Cell, Vol. 160, Issue 3
Production of resistant HIV mutants during antiretroviral therapy
journal, July 2000
- Ribeiro, R. M.; Bonhoeffer, S.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 14
Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection
journal, July 2014
- Wagner, T. A.; McLaughlin, S.; Garg, K.
- Science, Vol. 345, Issue 6196
Re-emergence of HIV after stopping therapy
journal, October 1999
- Chun, Tae-Wook; Davey, Richard T.; Engel, Delphine
- Nature, Vol. 401, Issue 6756
HIV rebounds from latently infected cells, rather than from continuing low-level replication
journal, October 2008
- Joos, B.; Fischer, M.; Kuster, H.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 43
A Novel Antiviral Intervention Results in More Accurate Assessment of Human Immunodeficiency Virus Type 1 Replication Dynamics and T-Cell Decay In Vivo
journal, April 2003
- Markowitz, M.; Louie, M.; Hurley, A.
- Journal of Virology, Vol. 77, Issue 8
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
journal, June 2009
- Chomont, Nicolas; El-Far, Mohamed; Ancuta, Petronela
- Nature Medicine, Vol. 15, Issue 8
Estimation of the Initial Viral Growth Rate and Basic Reproductive Number during Acute HIV-1 Infection
journal, March 2010
- Ribeiro, R. M.; Qin, L.; Chavez, L. L.
- Journal of Virology, Vol. 84, Issue 12
Different Dynamics of CD4 + and CD8 + T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection
journal, October 2003
- De Boer, Rob J.; Homann, Dirk; Perelson, Alan S.
- The Journal of Immunology, Vol. 171, Issue 8
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
journal, October 2013
- Ho, Ya-Chi; Shan, Liang; Hosmane, Nina N.
- Cell, Vol. 155, Issue 3
Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy
journal, May 2009
- Dinoso, J. B.; Kim, S. Y.; Wiegand, A. M.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 23
Exact stochastic simulation of coupled chemical reactions
journal, December 1977
- Gillespie, Daniel T.
- The Journal of Physical Chemistry, Vol. 81, Issue 25
Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection
journal, July 1998
- Chun, T. -W.; Engel, D.; Berrey, M. M.
- Proceedings of the National Academy of Sciences, Vol. 95, Issue 15
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996
- Perelson, A. S.; Neumann, A. U.; Markowitz, M.
- Science, Vol. 271, Issue 5255
Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques
journal, November 2007
- Chen, H. Y.; Di Mascio, M.; Perelson, A. S.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 48
Modeling Plasma Virus Concentration during Primary HIV Infection
journal, April 2000
- Stafford, Max A.; Corey, Lawrence; Cao, Yunzhen
- Journal of Theoretical Biology, Vol. 203, Issue 3
Residual HIV-1 RNA in Blood Plasma of Patients Taking Suppressive Highly Active Antiretroviral Therapy
journal, November 1999
- Dornadula, Geethanjali
- JAMA, Vol. 282, Issue 17
HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission
journal, July 2015
- Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin
- PLOS Pathogens, Vol. 11, Issue 7
Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells
journal, June 2006
- Bailey, J. R.; Sedaghat, A. R.; Kieffer, T.
- Journal of Virology, Vol. 80, Issue 13
Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues
journal, September 2010
- De Boer, Rob J.; Ribeiro, Ruy M.; Perelson, Alan S.
- PLoS Computational Biology, Vol. 6, Issue 9
A Randomized, Controlled Trial of Raltegravir Intensification in Antiretroviral-treated, HIV-infected Patients with a Suboptimal CD4+ T Cell Response
journal, April 2011
- Hatano, Hiroyu; Hayes, Timothy L.; Dahl, Viktor
- The Journal of Infectious Diseases, Vol. 203, Issue 7
An Increasing Proportion of Monotypic HIV-1 DNA Sequences during Antiretroviral Treatment Suggests Proliferation of HIV-Infected Cells
journal, November 2012
- Wagner, Thor A.; McKernan, Jen L.; Tobin, Nicole H.
- Journal of Virology, Vol. 87, Issue 3
Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans
journal, September 2013
- Westera, Liset; Drylewicz, Julia; den Braber, Ineke
- Blood, Vol. 122, Issue 13
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis
journal, November 1999
- Ramratnam, Bharat; Bonhoeffer, Sebastian; Binley, James
- The Lancet, Vol. 354, Issue 9192
Short‐Course Raltegravir Intensification Does Not Reduce Persistent Low‐Level Viremia in Patients with HIV‐1 Suppression during Receipt of Combination Antiretroviral Therapy
journal, March 2010
- McMahon, D.; Jones, J.; Wiegand, A.
- Clinical Infectious Diseases, Vol. 50, Issue 6
Modelling HIV-1 2-LTR dynamics following raltegravir intensification
journal, July 2013
- Luo, Rutao; Cardozo, E. Fabian; Piovoso, Michael J.
- Journal of The Royal Society Interface, Vol. 10, Issue 84
HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy
journal, July 2001
- Hermankova, Monika
- JAMA, Vol. 286, Issue 2
Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1
journal, August 2014
- Hill, Alison L.; Rosenbloom, Daniel I. S.; Fu, Feng
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 37
Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys
journal, July 2014
- Whitney, James B.; Hill, Alison L.; Sanisetty, Srisowmya
- Nature, Vol. 512, Issue 7512
Genotypic Analysis of HIV‐1 Drug Resistance at the Limit of Detection: Virus Production without Evolution in Treated Adults with Undetectable HIV Loads
journal, April 2004
- Kieffer, Tara L.; Finucane, Mariel M.; Nettles, Richard E.
- The Journal of Infectious Diseases, Vol. 189, Issue 8
Specific HIV integration sites are linked to clonal expansion and persistence of infected cells
journal, June 2014
- Maldarelli, F.; Wu, X.; Su, L.
- Science, Vol. 345, Issue 6193
Nonlinear Oscillations, Dynamical Systems, and Bifurcations of Vector Fields
book, January 1983
- Guckenheimer, John; Holmes, Philip
- Applied Mathematical Sciences
Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in HIV-infected Patients on Potent Therapy
journal, October 2009
- Rong, Libin; Perelson, Alan S.
- PLoS Computational Biology, Vol. 5, Issue 10
Reservoirs for HIV-1: Mechanisms for Viral Persistence in the Presence of Antiviral Immune Responses and Antiretroviral Therapy
journal, April 2000
- Pierson, Theodore; McArthur, Justin; Siliciano, Robert F.
- Annual Review of Immunology, Vol. 18, Issue 1
Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection
journal, February 2012
- Evering, Teresa H.; Mehandru, Saurabh; Racz, Paul
- PLoS Pathogens, Vol. 8, Issue 2
Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells
journal, May 2003
- Siliciano, Janet D.; Kajdas, Joleen; Finzi, Diana
- Nature Medicine, Vol. 9, Issue 6
Treatment-Mediated Alterations in HIV Fitness Preserve CD4+ T Cell Counts but Have Minimal Effects on Viral Load
journal, November 2010
- Vaidya, Naveen K.; Rong, Libin; Marconi, Vincent C.
- PLoS Computational Biology, Vol. 6, Issue 11
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection
journal, May 1997
- Chun, Tae-Wook; Carruth, Lucy; Finzi, Diana
- Nature, Vol. 387, Issue 6629
The Challenge of Finding a Cure for HIV Infection
journal, March 2009
- Richman, D. D.; Margolis, D. M.; Delaney, M.
- Science, Vol. 323, Issue 5919
Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy
journal, May 1999
- Finzi, Diana; Blankson, Joel; Siliciano, Janet D.
- Nature Medicine, Vol. 5, Issue 5
Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs
journal, November 2009
- Coiras, Mayte; López-Huertas, María Rosa; Pérez-Olmeda, Mayte
- Nature Reviews Microbiology, Vol. 7, Issue 11
The distribution of time to extinction in subcritical branching processes: applications to outbreaks of infectious disease
journal, September 1999
- Farrington, C. P.; Grant, A. D.
- Journal of Applied Probability, Vol. 36, Issue 03
Persistence by proliferation?
journal, July 2014
- Margolis, D.; Bushman, F.
- Science, Vol. 345, Issue 6193
Relationship Between Residual Plasma Viremia and the Size of HIV Proviral DNA Reservoirs in Infected Individuals Receiving Effective Antiretroviral Therapy
journal, July 2011
- Chun, Tae-Wook; Murray, Danielle; Justement, J. Shawn
- The Journal of Infectious Diseases, Vol. 204, Issue 1
Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection
journal, May 2012
- Archin, N. M.; Vaidya, N. K.; Kuruc, J. D.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 24
Constant Mean Viral Copy Number per Infected Cell in Tissues Regardless of High, Low, or Undetectable Plasma HIV RNA
journal, May 1999
- Hockett, Richard D.; Michael Kilby, J.; Derdeyn, Cynthia A.
- The Journal of Experimental Medicine, Vol. 189, Issue 10
ART Suppresses Plasma HIV-1 RNA to a Stable Set Point Predicted by Pretherapy Viremia
journal, January 2007
- Maldarelli, Frank; Palmer, Sarah; King, Martin S.
- PLoS Pathogens, Vol. 3, Issue 4
Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues
journal, January 2014
- Fletcher, Courtney V.; Staskus, Kathryn; Wietgrefe, Stephen W.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 6
Antiretroviral dynamics determines HIV evolution and predicts therapy outcome
journal, September 2012
- Rosenbloom, Daniel I. S.; Hill, Alison L.; Rabi, S. Alireza
- Nature Medicine, Vol. 18, Issue 9
Asymmetric division of activated latently infected cells may explain the decay kinetics of the HIV-1 latent reservoir and intermittent viral blips
journal, January 2009
- Rong, Libin; Perelson, Alan S.
- Mathematical Biosciences, Vol. 217, Issue 1
Induction of HIV-1 Replication in Latently Infected CD4 + T Cells Using a Combination of Cytokines
journal, July 1998
- Chun, Tae-Wook; Engel, Delphine; Mizell, Stephanie B.
- The Journal of Experimental Medicine, Vol. 188, Issue 1
Immediate antiviral therapy appears to restrict resting CD4 + cell HIV-1 infection without accelerating the decay of latent infection
text, January 2012
- N. M., Archin,; J. M., Coffin,; A., Wiegand,
- The University of North Carolina at Chapel Hill University Libraries
Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4+ T Cells
text, January 2011
- R., Swanstrom,; A., Wiegand,; W., Ince,
- The University of North Carolina at Chapel Hill University Libraries
HIV rebounds from latently infected cells, rather than from continuing low-level replication
text, January 2008
- Joos, B.; Fischer, M.; Kuster, H.
- National Academy of Sciences
Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy
journal, February 2001
- Pomerantz, R. J.
- Biomedicine & Pharmacotherapy, Vol. 55, Issue 1
The distribution of time to extinction in subcritical branching processes: applications to outbreaks of infectious disease
journal, September 1999
- Farrington, C. P.; Grant, A. D.
- Journal of Applied Probability, Vol. 36, Issue 3
Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection
text, January 2012
- D., Kuruc, J.; S., Cohen, M.; M., Coffin, J.
- The University of North Carolina at Chapel Hill University Libraries
Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1
text, January 2014
- Hill, Alison L.; Rosenbloom, Daniel I. S.; Fu, Feng
- arXiv
HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy
journal, July 2001
- Hermankova, Monika
- JAMA, Vol. 286, Issue 2
Modeling Plasma Virus Concentration during Primary HIV Infection
journal, April 2000
- Stafford, Max A.; Corey, Lawrence; Cao, Yunzhen
- Journal of Theoretical Biology, Vol. 203, Issue 3
Dynamics of HIV infection of CD4+ T cells
journal, March 1993
- Perelson, Alan S.; Kirschner, Denise E.; De Boer, Rob
- Mathematical Biosciences, Vol. 114, Issue 1
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
journal, October 2013
- Ho, Ya-Chi; Shan, Liang; Hosmane, Nina N.
- Cell, Vol. 155, Issue 3
HIV-1 Integration Landscape during Latent and Active Infection
journal, January 2015
- Cohn, Lillian B.; Silva, Israel T.; Oliveira, Thiago Y.
- Cell, Vol. 160, Issue 3
Asymmetric division of activated latently infected cells may explain the decay kinetics of the HIV-1 latent reservoir and intermittent viral blips
journal, January 2009
- Rong, Libin; Perelson, Alan S.
- Mathematical Biosciences, Vol. 217, Issue 1
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection
journal, May 1997
- Chun, Tae-Wook; Carruth, Lucy; Finzi, Diana
- Nature, Vol. 387, Issue 6629
Re-emergence of HIV after stopping therapy
journal, October 1999
- Chun, Tae-Wook; Davey, Richard T.; Engel, Delphine
- Nature, Vol. 401, Issue 6756
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
journal, June 2009
- Chomont, Nicolas; El-Far, Mohamed; Ancuta, Petronela
- Nature Medicine, Vol. 15, Issue 8
Antiretroviral dynamics determines HIV evolution and predicts therapy outcome
journal, September 2012
- Rosenbloom, Daniel I. S.; Hill, Alison L.; Rabi, S. Alireza
- Nature Medicine, Vol. 18, Issue 9
Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells
journal, May 2003
- Siliciano, Janet D.; Kajdas, Joleen; Finzi, Diana
- Nature Medicine, Vol. 9, Issue 6
Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs
journal, November 2009
- Coiras, Mayte; López-Huertas, María Rosa; Pérez-Olmeda, Mayte
- Nature Reviews Microbiology, Vol. 7, Issue 11
Directed cell migration towards softer environments
journal, July 2022
- Isomursu, Aleksi; Park, Keun-Young; Hou, Jay
- Nature Materials, Vol. 21, Issue 9
Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques
journal, November 2007
- Chen, H. Y.; Di Mascio, M.; Perelson, A. S.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 48
Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy
journal, May 2009
- Dinoso, J. B.; Kim, S. Y.; Wiegand, A. M.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 23
Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection
journal, May 2012
- Archin, N. M.; Vaidya, N. K.; Kuruc, J. D.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 24
Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues
journal, January 2014
- Fletcher, Courtney V.; Staskus, Kathryn; Wietgrefe, Stephen W.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 6
Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection
journal, July 1998
- Chun, T. -W.; Engel, D.; Berrey, M. M.
- Proceedings of the National Academy of Sciences, Vol. 95, Issue 15
HIV therapy: Managing resistance
journal, July 2000
- Wodarz, Dominik; Nowak, Martin A.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 15
Induction of HIV-1 Replication in Latently Infected CD4 + T Cells Using a Combination of Cytokines
journal, July 1998
- Chun, Tae-Wook; Engel, Delphine; Mizell, Stephanie B.
- The Journal of Experimental Medicine, Vol. 188, Issue 1
Constant Mean Viral Copy Number per Infected Cell in Tissues Regardless of High, Low, or Undetectable Plasma HIV RNA
journal, May 1999
- Hockett, Richard D.; Michael Kilby, J.; Derdeyn, Cynthia A.
- The Journal of Experimental Medicine, Vol. 189, Issue 10
Genotypic Analysis of HIV‐1 Drug Resistance at the Limit of Detection: Virus Production without Evolution in Treated Adults with Undetectable HIV Loads
journal, April 2004
- Kieffer, Tara L.; Finucane, Mariel M.; Nettles, Richard E.
- The Journal of Infectious Diseases, Vol. 189, Issue 8
Short‐Course Raltegravir Intensification Does Not Reduce Persistent Low‐Level Viremia in Patients with HIV‐1 Suppression during Receipt of Combination Antiretroviral Therapy
journal, March 2010
- McMahon, D.; Jones, J.; Wiegand, A.
- Clinical Infectious Diseases, Vol. 50, Issue 6
A Randomized, Controlled Trial of Raltegravir Intensification in Antiretroviral-treated, HIV-infected Patients with a Suboptimal CD4+ T Cell Response
journal, April 2011
- Hatano, Hiroyu; Hayes, Timothy L.; Dahl, Viktor
- The Journal of Infectious Diseases, Vol. 203, Issue 7
Incomplete adherence to antiretroviral therapy is associated with higher levels of residual HIV-1 viremia
journal, January 2014
- Li, Jonathan Z.; Gallien, Sebastien; Ribaudo, Heather
- AIDS, Vol. 28, Issue 2
Early HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b)
journal, January 2015
- Andrade, Adriana; Guedj, Jeremie; Rosenkranz, Susan L.
- AIDS, Vol. 29, Issue 18
Sustained Antiretroviral Effect of Raltegravir After 96 Weeks of Combination Therapy in Treatment-Naive Patients With HIV-1 Infection
journal, November 2009
- Markowitz, Martin; Nguyen, Bach-Yen; Gotuzzo, Eduardo
- JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 52, Issue 3
Persistence by proliferation?
journal, July 2014
- Margolis, D.; Bushman, F.
- Science, Vol. 345, Issue 6193
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996
- Perelson, A. S.; Neumann, A. U.; Markowitz, M.
- Science, Vol. 271, Issue 5255
Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4+ T Cells
journal, March 2011
- Anderson, J. A.; Archin, N. M.; Ince, W.
- Journal of Virology, Vol. 85, Issue 10
Viral Dynamics during Primary Simian Immunodeficiency Virus Infection: Effect of Time-Dependent Virus Infectivity
journal, February 2010
- Vaidya, N. K.; Ribeiro, R. M.; Miller, C. J.
- Journal of Virology, Vol. 84, Issue 9
Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues
journal, September 2010
- De Boer, Rob J.; Ribeiro, Ruy M.; Perelson, Alan S.
- PLoS Computational Biology, Vol. 6, Issue 9
Treatment-Mediated Alterations in HIV Fitness Preserve CD4+ T Cell Counts but Have Minimal Effects on Viral Load
journal, November 2010
- Vaidya, Naveen K.; Rong, Libin; Marconi, Vincent C.
- PLoS Computational Biology, Vol. 6, Issue 11
Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection
journal, February 2012
- Evering, Teresa H.; Mehandru, Saurabh; Racz, Paul
- PLoS Pathogens, Vol. 8, Issue 2
HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission
journal, July 2015
- Pinkevych, Mykola; Cromer, Deborah; Tolstrup, Martin
- PLOS Pathogens, Vol. 11, Issue 7
How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?
text, January 2015
- Karine, Dubé,; Nicolas, Chomont,; Jintanat, Ananworanich,
- The University of North Carolina at Chapel Hill University Libraries
Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study
journal, January 2011
- Llibre, Josep M.; Buzón, Maria J.; Massanella, Marta
- Antiviral Therapy, Vol. 17, Issue 2
Different Dynamics of CD4 + and CD8 + T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection
journal, October 2003
- De Boer, Rob J.; Homann, Dirk; Perelson, Alan S.
- The Journal of Immunology, Vol. 171, Issue 8
Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1
text, January 2014
- Hill, Alison L.; Rosenbloom, Daniel I. S.; Fu, Feng
- arXiv
Works referencing / citing this record:
Re-evaluating evolution in the HIV reservoir
journal, November 2017
- Rosenbloom, Daniel I. S.; Hill, Alison L.; Laskey, Sarah B.
- Nature, Vol. 551, Issue 7681
Anti-proliferative therapy for HIV cure: a compound interest approach
journal, June 2017
- Reeves, Daniel B.; Duke, Elizabeth R.; Hughes, Sean M.
- Scientific Reports, Vol. 7, Issue 1
Probabilistic control of HIV latency and transactivation by the Tat gene circuit
journal, November 2018
- Cao, Youfang; Lei, Xue; Ribeiro, Ruy M.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 49
Modelling the evolution of HIV ‐1 virulence in response to imperfect therapy and prophylaxis
journal, February 2017
- Smith, David R. M.; Mideo, Nicole
- Evolutionary Applications, Vol. 10, Issue 3
Determinants of the efficacy of HIV latency-reversing agents and implications for drug and treatment design
journal, October 2018
- Ke, Ruian; Conway, Jessica M.; Margolis, David M.
- JCI Insight, Vol. 3, Issue 20
Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics
journal, October 2016
- Lythgoe, Katrina A.; Blanquart, François; Pellis, Lorenzo
- PLOS Biology, Vol. 14, Issue 10
Predictions of time to HIV viral rebound following ART suspension that incorporate personal biomarkers
journal, July 2019
- Conway, Jessica M.; Perelson, Alan S.; Li, Jonathan Z.
- PLOS Computational Biology, Vol. 15, Issue 7
CD8+ lymphocyte control of SIV infection during antiretroviral therapy
journal, October 2018
- Cao, Youfang; Cartwright, Emily K.; Silvestri, Guido
- PLOS Pathogens, Vol. 14, Issue 10
Determinants of the efficacy of HIV latency-reversing agents and implications for drug and treatment design
text, January 2018
- D. M., Margolis,; R., Ke,; A. S., Perelson,
- NLM (Medline)
Towards multiscale modeling of the CD8
+
T cell response to viral infections
journal, February 2019
- Baral, Subhasish; Raja, Rubesh; Sen, Pramita
- WIREs Systems Biology and Medicine, Vol. 11, Issue 4
Persistent HIV-1 replication during antiretroviral therapy
journal, January 2016
- Martinez-Picado, Javier; Deeks, Steven G.
- Current Opinion in HIV and AIDS, Vol. 11, Issue 4
Modelling the evolution of HIV ‐1 virulence in response to imperfect therapy and prophylaxis
journal, February 2017
- Smith, David R. M.; Mideo, Nicole
- Evolutionary Applications, Vol. 10, Issue 3
Mathematical modeling to reveal breakthrough mechanisms in the HIV Antibody Mediated Prevention (AMP) trials
journal, February 2020
- Reeves, Daniel B.; Huang, Yunda; Duke, Elizabeth R.
- PLOS Computational Biology, Vol. 16, Issue 2
CD8+ lymphocyte control of SIV infection during antiretroviral therapy
journal, October 2018
- Cao, Youfang; Cartwright, Emily K.; Silvestri, Guido
- PLOS Pathogens, Vol. 14, Issue 10
Modeling Kick-Kill Strategies toward HIV Cure
journal, August 2017
- Hernandez-Vargas, Esteban A.
- Frontiers in Immunology, Vol. 8