ArticleJournal of theoretical biology2014
Spatial modeling of HIV cryptic viremia and 2-LTR formation during raltegravir intensification.
Article in Journal of theoretical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025Article
- Ongoing HIV replication in lymph node sanctuary sites in treated individuals contributes to the total latent HIV at a very slow rate.Journal of theoretical biology · 2023Article
- Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression.Cellular and molecular bioengineering · 2020Article
- An Integrated Spatial Dynamics-Pharmacokinetic Model Explaining Poor Penetration of Anti-retroviral Drugs in Lymph Nodes.Frontiers in bioengineering and biotechnology · 2020Article
- Positive feedback through inflammation creates bistable behavior in HIV tissue sanctuaries.Proceedings of the ... American Control Conference. American Control Conference · 2019Article
- Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion.Nature communications · 2019Article
- Persistent HIV-1 Viremia on Antiretroviral Therapy: Measurement and Mechanisms.Frontiers in microbiology · 2019Review
- Episomal HIV-1 DNA and its relationship to other markers of HIV-1 persistence.Retrovirology · 2018Review
- HIV 2-LTR experiment design optimization.PloS one · 2018Article
- Order preservation of expected information content using Unscented Transform approximation of multivariate prior distributions in HIV 2-LTR experiment design.Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control · 2016Article
- Increased inflammation in sanctuary sites may explain viral blips in HIV infection.IET systems biology · 2016Article
- Persistent HIV-1 replication during antiretroviral therapy.Current opinion in HIV and AIDS · 2016Review
- Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Authors and funding
4 authors.
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Abstract
Combination Antiretroviral Therapy (cART) can suppress plasma HIV below the limit of detection in normal assays. Recently reported results suggest that viral replication may continue in some patients, despite undetectable levels in the blood. It has been suggested that the appearance of the circularized episomal HIV DNA artifact 2-LTR following treatment intensification with the integrase inhibitor raltegravir is a marker of ongoing viral replication. Other work has suggested that lymphoid organs may be a site of reduced antiviral penetration and increased viral production. In this study we model the hypothesis that this ongoing replication occurs in lymphoid follicle sanctuary sites and investigate the patterns of 2-LTR formation expected after raltegravir application. Experimental data is used to estimate the reaction and diffusion parameters in the model, and Monte-Carlo simulations are used to explore model behavior subject to variation in these rates. The results suggest that conditions for the formation of an observed transient peak in 2-LTR formation following raltegravir intensification include a sanctuary site diameter larger than 0.2mm, a viral basic reproductive ratio within the site larger than 1, and a total volume of active sanctuary sites above 20mL. Significant levels of uncontrolled replication can occur in the sanctuary sites without measurable changes in the plasma viral load. By contrast, subcritical replication (where the basic reproductive ratio of the virus is less than 1 in all sites) always results in monotonic increases of measured 2-LTR following raltegravir intensification, occurring at levels below the limit of detection.
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