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          Institute: MPI für Meteorologie     Collection: Atmosphere in the Earth System     Display Documents

ID: 255912.0, MPI für Meteorologie / Atmosphere in the Earth System
Impact of gene-modified T cells on HIV infection dynamics
Authors:von Laer, Dorothee; Hasselmann, Susanne; Hasselmann, Klaus F.
Date of Publication (YYYY-MM-DD):2006-01
Title of Journal:Journal of Theoretical Biology
Start Page:60
End Page:77
Copyright:2005 Elsevier Ltd. All rights reserved.
Review Status:not specified
Audience:Not Specified
Abstract / Description:Previous clinical trials in HIV-infected patients involving infusion of T cells protected by an antiviral gene have failed to show any
therapeutic benefit. The value of such a treatment approach is thus still highly controversial. In this study, the anticipated effects of
gene-modified cells on virus and T-cell kinetics are analysed by mathematical modeling. Because technically only a small fraction of
all T cells in a patient can be manipulated ex vivo, therapeutic success will depend on the accumulation of gene-modified cells after
infusion into the patient by in vivo selection. Our simulations predict that a significant therapeutic benefit is conferred only by
antiviral genes that inhibit HIV replication before virus integration (class I genes). Genes that inhibit viral protein expression (class
II, used in previous clinical trials), require a much higher inhibitory activity than class I genes to promote the regeneration of T cells
and reduce the viral load. Inhibition of virus assembly and release alone (class III) confers no selective advantage to the T cell and is
therefore ineffective unless combined with class I (or, possibly, class II) genes. Also crucial in determining the clinical outcome are
the regenerative capacity of the gene-modified cells and the level of HIV replication in the patient. These results can be important for
guiding future strategies in the field of gene therapy for HIV infection.
Free Keywords:HIV infection; Antiviral gene; T cell transfer; Mathematical model
External Publication Status:published
Document Type:Article
Communicated by:Carola Kauhs
Affiliations:MPI für Meteorologie/Emeriti
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