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TreatmentUpdate 172

Volume 21 Issue 3

2009 March/April

I ANTI-HIV AGENTS - F. Gene therapy

In high-income countries, HAART became available in 1996. HAART has greatly reduced deaths from AIDS-related infections. As a result, HIV positive people who do not have serious co-existing health conditions and who are engaged in their care and treatment are likely to have near-normal life spans.

HAART has enabled people to liver longer lives. However, HAART is not the ideal solution for HIV treatment for the following reasons:

This therapy has to be taken every day, once or twice daily, for the rest of a person’s life. Taking HAART every day as directed is a behaviour called adherence. No one knows how long the high levels of adherence needed for HAART’s success can be sustained.
HAART causes side effects, both long- and short-term.
HIV can develop resistance to HAART, reducing future treatment options.

All of these points generate interest in developing simpler, safer HIV therapy and even a cure.

Harnessing the immune system

Since the beginning of the AIDS pandemic, scientists have dreamt of ways to make the immune system more easily resist HIV. In the past 15 years research teams in high-income countries have been conducting experiments involving gene therapy in their labs and, in some cases, in HIV positive volunteers.

The code for life

Cells contain genes, which in turn contain DNA—the code for life. DNA contains instructions that tell cells how to work: to make proteins and enzymes, perform repairs, build new cells and so on. Genes can be turned off and on as needed.

Gene therapy is currently being tested to try to correct such conditions as hemophilia, cardiovascular disease, Parkinson’s disease and HIV infection.

How it works

Genes can’t simply be injected into cells; they have to be delivered by a vector (a carrier). The most commonly used vector is a virus. This is because viruses are very good at getting into cells and inserting the viral genes into the cell’s DNA. For gene therapy experiments, scientists take viruses, sometimes mouse viruses, and weaken them, removing their capacity to cause disease. Once this is done, technicians then insert the genes that they want to be transferred to people into the virus or vector. Further details about the transfer of genes appear in our next story.

Caution

Gene therapy can carry risks. For instance, sometimes the new genes carried by the weakened virus may get inserted into a cell’s DNA near genes that can help trigger the growth and development of tumours. If the new genes get turned on, cancer-causing genes already present in human cells may also become active. However, there have been many clinical trials of gene therapy for several disorders and the number of deaths has been very low. Moreover, in clinical trials with HIV positive volunteers, nobody has died because of the transfer of genes.

Next we have a report on the latest trial of gene therapy for HIV infection.

REFERENCES:

1. Rossi JJ, June CH, Kohn DB. Genetic therapies against HIV. Nature Biotechnology. 2007 Dec;25(12):1444-54.

2. Levine BL, Mosca JD, Riley JL, et al. Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation. Science 1996 Jun 28;272(5270):1939-43.

3. Amado RG, Mitsuyasu RT, Rosenblatt JD, et al. Anti-human immunodeficiency virus hematopoietic progenitor cell-delivered ribozyme in a phase I study: myeloid and lymphoid reconstitution in human immunodeficiency virus type-1-infected patients. Human Gene Therapy. 2004 Mar;15(3):251-62.

4. Macpherson JL, Boyd MP, Arndt AJ, et al. Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients. Journal of Gene Medicine. 2005 May;7(5):552-64.

5. Williams DA. NIH recombinant DNA Advisory Committee continues to ponder adverse event associated with AAV gene therapy trial. Molecular Therapy. 2008 Mar;16(3):427-8.

6. Mitsuyasu R, Merigan T, Carr A, et al. Safety and efficacy of autologous CD34+ hematopoietic progenitor cells transduced with retroviral vector containing a ribozyme directed against the HIV-1 tat gene, OZ1, in a multicenter, randomized, placebo-controlled Phase II Trial. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal, Canada. Abstract 581.

7. Kohn DB, Candotti F. Gene therapy: fulfilling its promise. New England Journal of Medicine. 2009 Jan 29;360(5):518-21.

Created on: 2009 May 1

Author: Hosein SR

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