ArticleCPT: pharmacometrics & systems pharmacology2016
Mechanistic Models Predict Efficacy of CCR5-Deficient Stem Cell Transplants in HIV Patient Populations.
Article in CPT: pharmacometrics & systems pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Promising Stem Cell therapy in the Management of HIV and AIDS: A Narrative Review.Biologics : targets & therapy · 2022Review
- History and Future Perspectives on the Discipline of Quantitative Systems Pharmacology Modeling and Its Applications.Frontiers in physiology · 2021Review
- A Quantitative Systems Pharmacology Model of Gaucher Disease Type 1 Provides Mechanistic Insight Into the Response to Substrate Reduction Therapy With Eliglustat.CPT: pharmacometrics & systems pharmacology · 2020Article
- The Spectrum of Mechanism-Oriented Models and Methods for Explanations of Biological Phenomena.Processes (Basel, Switzerland) · 2018Article
- Linear-In-Flux-Expressions Methodology: Toward a Robust Mathematical Framework for Quantitative Systems Pharmacology Simulators.Gene regulation and systems biology · 2017Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination antiretroviral therapy (cART) effectively suppresses viral load in HIV-infected individuals, but it is not a cure. Bone marrow transplants using HIV-resistant stem cells have renewed hope that cure is achievable but key questions remain e.g., what percentage of stem cells must be HIV-resistant to achieve cure?. As few patients have undergone transplants, we built a mechanistic model of HIV/AIDS to approach this problem. The model includes major players of infection, reproduces the complete course of the disease, and simulates crucial components of clinical treatments, such as cART, irradiation, host recovery, gene augmentation, and donor chimerism. Using clinical data from 172 cART-naïve HIV-infected individuals, we created virtual populations to predict performance of CCR5-deficient stem-cell therapies and explore interpatient variability. We validated our model against a published clinical study of CCR5-modified T-cell therapy. Our model predicted that donor chimerism must exceed 75% to achieve 90% probability of cure across patient populations.
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Registered trials
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