Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect.
This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.
Lund
O
O
Laboratory for infectious Diseases, Hvidovre Hospital, University of Copenhagen, Denmark. infejesh@inet.uni-c.dk
Lund
O S
OS
Gram
G
G
Nielsen
S D
SD
Schønning
K
K
Nielsen
J O
JO
Hansen
J E
JE
Mosekilde
E
E
D016923:Cell Death; D015316:Genetic Therapy; D015658:HIV Infections / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008433:Mathematics; D008954:Models, Biological; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology / Q000821:virology; D014161:Transduction, Genetic