Mathematical modeling of optimal therapeutic combinations for HIV cure
HIV治愈最佳治疗组合的数学模型
基本信息
- 批准号:10312707
- 负责人:
- 金额:$ 9.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-12-16 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAcquired Immunodeficiency SyndromeAcuteAdultAftercareAgreementCAR T cell therapyCD4 Positive T LymphocytesCaringCell TherapyCellsCharacteristicsChronicClinicClinical TrialsCollaborationsCombined Modality TherapyConsensusConsumptionDataDoseDrug KineticsEncapsulatedFosteringFred Hutchinson Cancer Research CenterGene-ModifiedGenetic VariationGoalsHIVHIV InfectionsHIV antiretroviralHIV therapyHealthHomeHumanImmunologicsIndividualInfrastructureInfusion proceduresIngestionInterruptionInterventionInvestigationKineticsLinkLongevityLymphocyteMilitary PersonnelMissionModelingOutcomeOutcome MeasurePatternPeptide antibodiesPersonsProbabilityPublic HealthResearchResearch PersonnelRunningSafetyScheduleSiteTestingTherapeuticTimeTrainingTranslationsTreatment EfficacyUnited States National Institutes of HealthVaccinationVaccine TherapyViralVirus Replicationantiproliferative agentsantiretroviral therapycare costscollaboratorycombinatorialcontrol theorycurative treatmentsdesigneffective interventionexperimental studygene therapygene transplantation for gene therapyin silicoin vivoinnovationmathematical modelmultimodalitynanoparticlenonhuman primatepillpreventprocess optimizationprogramsresponsesimulationsocial stigmastemstem cellssynthetic antibodiestheoriestransmission processtreatment durationviral rebound
项目摘要
PROJECT SUMMARY
Antiretroviral therapy (ART) suppresses HIV replication and allows a normal lifespan for infected persons, but
daily pill ingestion is required to avoid progression to AIDS and further HIV transmission. Multiple therapeutic
strategies are being considered to achieve a functional cure for HIV. However, to date, no single approach has
achieved sufficient potency for an HIV functional cure. Therefore, there is increasing agreement that an HIV cure
will require a multi-pronged approach. This proposal has the objective to identify optimal and feasible
combinations of investigational therapeutic approaches to achieve functional cure of HIV using data-validated
mathematical models. Our hypothesis is that data-validated mathematical models can identify specific
mechanisms of therapeutic combinations, by linking observed kinetics and potency with various quantifiable
outcome measures. Our specific aims will validate this hypothesis by fitting different mathematical models that
encapsulate competing possible mechanisms to outcome data from curative interventions currently under study,
including levels of different reservoir cellular subset, viral quantities, viral diversity and time to viral rebound.
Model selection theory will be used to identify the most parsimonious models that reliably explain experimental
results. We will use the most parsimonious model that recapitulated the data from each study to perform in silico
experiments. We will list all plausible combinations of therapeutic approaches and model each combination. We
will create combinatorial dose-response curves by running simulations for each combination by using the
parameterization obtained from the fits and by tuning the parameters for each therapy including dosing,
scheduling, and order of treatment. This proposal is significant because testing all possible combinations of
approaches is impractical, excessively time consuming and expensive. The inability to rigorously assess all
potential approaches is a critical barrier to achieve optimal outcomes. Therefore, our proposal is innovative
because we propose a rigorous, quantitative framework in which plausible combinations of available
interventions are considered and compared with the potential to identify which combination therapies most likely
will achieve a functional cure.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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Erwing Fabian Cardozo Ojeda其他文献
Cervicovaginal tissue residence imprints a distinct differentiation program upon memory CD8 T cells
宫颈阴道组织驻留给记忆 CD8 T 细胞留下了独特的分化程序印记
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Veronica A. Davé;Erwing Fabian Cardozo Ojeda;F. Mair;J. Erickson;Amanda S. Woodward;A. Soerens;A. Koehne;Julie L. Czartoski;Candice Teague;Nicole B. Potchen;Susanne G. Oberle;D. Zehn;J. Schiffer;Jennifer M. Lund;Martin Prlic - 通讯作者:
Martin Prlic
Erwing Fabian Cardozo Ojeda的其他文献
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{{ truncateString('Erwing Fabian Cardozo Ojeda', 18)}}的其他基金
Mathematical modeling of optimal therapeutic combinations for HIV cure
HIV治愈最佳治疗组合的数学模型
- 批准号:
10593449 - 财政年份:2019
- 资助金额:
$ 9.55万 - 项目类别:
Mathematical modeling of optimal therapeutic combinations for HIV cure
HIV治愈最佳治疗组合的数学模型
- 批准号:
9927445 - 财政年份:2019
- 资助金额:
$ 9.55万 - 项目类别:
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