The Body: The Complete HIV/AIDS Resource
Follow Us Follow Us on Facebook Follow Us on Twitter Download Our App 
Professionals >> Visit The Body PROThe Body en Espanol
  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

Gene Therapy for HIV

July 2004

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!


Manipulating the body's cells and genes to treat disease holds great potential, but it is a field of research in its infancy. It will likely not yield results for years or perhaps decades as it takes baby steps towards progress. And although dramatic advances in treating HIV are not expected to come soon, its byproducts -- such as information about the immune system and HIV infection -- may contribute to short-term advances. This article provides an overview of the reasons for and challenges of gene therapy research.

Why Gene Therapy?

Your immune system includes many parts: thymus, lymph nodes, bone marrow, etc. The cells in your body are made from cells found in your bone marrow. One special cell found in bone marrow, called a stem cell, is sometimes called the mother of all cells. If your immune system is intact and working well, then a single stem cell could divide and populate the full range of cells in your body.

Imagine there's a gene that makes a cell resistant to HIV infection. In theory, if that gene was inserted into a stem cell, all of the offspring of that cell would carry the gene and be resistant to HIV infection.

Again, in theory, as HIV destroys a person's CD4+ and other immune cells, the new cells resistant to HIV would replace them and thrive. Eventually these newer cells would take over and HIV could no longer weaken the immune system. Although a person may still have HIV, it could do no harm. The HIV may just die out because there are no cells for it to infect; or, it might persist but couldn't harm the immune system to any great degree.

The Challenges

The success of using gene therapy to treat HIV rests on some important assumptions. The first is that all parts of the immune system must be intact in order to support the stem cells in repopulating the system. However, some researchers suspect that HIV may damage the thymus. So, at some point in a person's HIV disease the thymus may not help develop new healthy CD4+ cells. Other therapies may need to be used to improve or enhance damaged immune environments (such as the thymus or bone marrow) in order for gene therapy to be successful.

Assuming that the thymus, bone marrow and other immune environments are functioning well, the next challenge is finding a gene that makes a cell resistant to HIV infection. Once it has been identified, it's necessary to get that gene into a cell. Some researchers are experimenting with injecting these genes directly into muscle, called direct DNA injection. However, most researchers believe that the most effective way to get a gene into a cell is by "packaging" it into a virus. Viruses that scientists use to deliver genes, called vectors, include the Adeno-associated Virus (AAV) and maybe even crippled versions of HIV.

Getting a gene into a cell is no small feat. Not only must it be passed into the cell, but it must be done without harming it. It must also get into the gene without causing disease itself (and/or without combining with another virus, like HIV, and then causing disease).

In other gene therapy experiments for HIV, researchers have removed and genetically changed stem cells. However, when the new cells were infused back into the body, other immune cells detected that they had been altered and destroyed them. Therefore, it's not merely a matter of getting the gene into cells but doing it in a way that doesn't let the other cells target and destroy the new cells.

Once a stem cell is changed with a protective gene, and it remains functional and not targeted for destruction, the next challenge is making sure the stem cells begin dividing and that their offspring carry and use the protective gene. Of course, it's key that the new cells aren't also targeted and destroyed. While the ideal target for gene therapy may be stem cells, researchers are also looking at altering their offspring CD4+ cells. This would help rid at least one of the challenges in stem cell research.

The challenge of getting genes into cells occurs in all gene research, from HIV to cancer to genetic deficiencies. The solutions will probably come from combining the findings from these fields of research. However, there are still many concerns about safety, and they must be addressed carefully.

Work in Progress

Carl June at the University of Pennsylvania has reproduced CD4+ cells (not stem cells) that are resistant to HIV. His group has altered these cells with an HIV-based lentiviral vector that carries a gene targeting HIV, called HIV antisense. Together with ViRxSys, his group changed a large number of cells (above 90%) in the lab.

One small study is focusing on collecting safety information on five volunteers who have failed at least two anti-HIV regimens and have HIV levels above 5,000. They each will get one dose of these altered CD4+ cells. Their HIV levels and CD4+ cell counts will be checked along with the number of days that these cells persist.

Jan Van Luzen, through the Universities of Frankfurt and Hamburg in Germany, is developing a small study of gene therapy aimed at blocking HIV's entry into cells. (This is similar to the anti-HIV drug, T-20.) The gene is called M87oRRE and the vector being used is called myloproliferative sarcoma virus. Van Luzen will alter CD4+ cells using Carl June's methods. The study will enroll ten people who are resistant to all classes of anti-HIV therapy and have CD4+ cell counts below 200. The first volunteer was treated by injection in January 2004. So far, no data are available.

Researchers in the U.S. and Australia have developed a mid-sized study of gene therapy that targets the tat gene. The gene, called Rz2, is a hammerhead ribozyme and can potentially stop HIV at five places in its replication cycle. It is passed into stem cells using a retroviral vector, one that has already been evaluated for safety in over 50 studies.

This study will enroll over 70 people. Volunteers must have CD4+ cell counts above 300, and have been on anti-HIV therapy with HIV levels below 50 for at least six months. The study will include an interruption in anti-HIV therapy in order to assess the anti-HIV activity of the gene.

Data from a ten-person phase I study of this approach suggest that it's safe. (There were no safety concerns, and some volunteers have been followed for three years.) The Rz2 gene was found in the new cells in all volunteers. The study is enrolling at UC Los Angeles (Dr. Ron Mitsuyasu), UC Stanford (Dr. Tom Merigan), San Francisco (Dr. Steven Becker), and St. Vincent's in Sydney (Drs. Cooper and Carr).


Several studies using gene therapy to treat HIV have started over the past few years. Over the past decade, however, gene therapy research in general has been a rollercoaster of enthusiasm and disappointment. The darkest period struck just a few years ago when a volunteer in one experiment died due to complications from the procedure.

All human gene therapy research was stopped for nearly two years until the cause of death was evaluated and safety concerns were addressed. More recently there has been a renewed enthusiasm as gene therapy has successfully treated some other conditions. Advances in technology are also overcoming other challenges in the field.

Gene therapy research still faces many challenges, in addition to those outlined in this article. They include the need for increased public funding for biomedical research and the short-sightedness of biotech and drug companies investing in the future. It also includes the hurdles faced by independent researchers struggling to turn novel ideas into useful therapy for the patient.

Several years ago there was much enthusiasm for the RevM10 gene being researched in partnership with Systemix Corporation. Systemix was then bought by a larger drug company, and both gene therapy and HIV didn't fit into their development plan. The studies were stopped and the program was shut down.

Although gene therapy research won't offer a quick cure for AIDS, it is becoming an increasingly important part in the future of HIV treatment. It offers a new frontier for a cure, with great hope for promising new treatments.

Back to the Project Inform Perspective July 2004 contents page.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

This article was provided by Project Inform. It is a part of the publication Project Inform Perspective. Visit Project Inform's website to find out more about their activities, publications and services.
See Also
More on Gene Therapy for HIV/AIDS