Experimental Gene Therapy May Control HIV

November 12, 2012

Experimental Gene Therapy May Control HIV

Researchers say the next big step in HIV treatment is with mutant genes

Findings were presented to the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy which may give hope that a ‘functional cure’ is possible for HIV patients.

It was reported that a gene based ‘functional cure’ for HIV is a step closer and could mean that HIV patients no longer need drugs as part of their treatment. A ‘functional cure’ is a method of genetically modifying genes, in this case CD4 cells, to make them resistant to the virus.

Researchers point out that the patient remains infected with HIV but drugs are no longer needed to treat the condition. Because the CD4 cells have been modified, these are the cells which are targeted by the HIV virus, the viral attack becomes unsuccessful.

The research is only at an early stage but researcher Ronald T. Mitsuyasu, MD. Mitsuyasu, who is director of the University of California, Los Angeles Center for Clinical AIDS Research & Education explains that the treatment is safe and has been ‘well tolerated’ by the test participants.

Although some results were very good, other patients did not respond as effectively. In one patient his HIV levels were reduced to undetectable levels, and this was after his antiviral drugs were stopped. Mitsuyasu explains the benefits if a treatment can be formed without drugs and says, “If we can get the immune system to kick in and control the virus without drugs, that’s a win”.

Although in one patient the results were very good, in the other five patients the results were less impressive.

Find the Key Gene

The treatment involves extracting system cells related to the immune system from the patient, these cells are then modified and then returned to the patient. Presently the procedure is known as SB-728-T and it works by targeting the CCR5 gene. This is the gene that the HIV virus attacks, and hence allows the virus to enter the CD4 cells.

It is already known that some naturally produced CCR5 mutations turn the cells into HIV resistant cells. About 5% of people have this mutation with two copies which greatly enhances their resistance to HIV, it effectively makes them almost impervious to HIV. Another 10% of the population has only one copy of the mutation present. These people tend to a much slower timescale and the HIV grows at a much slower pace.

The 51st Interscience Conference had two studies presented to them. The studies lasted for about one year and involved fifteen patients. Although there were no serious side effects the researchers acknowledge that further long term work is required before the treatment’s safety can be guaranteed.

Antiviral drugs were not administered to six patients in one study for 12 weeks once they had completed the gene mutation treatment. It was found that only two patients showed no improvement. In the other cases three patients indicated a drop in HIV presence in their bodies and in one individual the levels of HIV dropped to a level where it was no longer detectable. This individual was one of the 10% of the population having a naturally occurring mutation with only one copy.

Researchers say that this indicates that the higher the number of mutant cells present in the body then the harder it is for the HIV to advance. They further point out that the patient, because of the naturally occurring mutation and the gene therapy had about twice the number of mutant cells present when compared to other patients.

The Future

Laurent Kaiser, MD, is the head of the virology laboratory at University Hospitals of Geneva in Switzerland. He is also on the committee that selected which studies were to be presented to the conference. He states that the research is still in the preliminary stages however, “he is convinced it’s a way to move forward”, once further work is done. It is only then that the studies can move from the laboratory to the bedside, he maintains. He also points out that the findings indicate, “It seems the number of modified cells is more important than previously reported”.

He goes on to explain that with antiviral drugs it is only the replication of the virus that is stopped. The virus is still present and the patient is still ill. When using a ‘functional cure’ there is a supply of cells which resist the spread of the virus and when these reproduce and multiply the virus can no longer endure.

The company funding the study is Sangamo Bioscience Inc. It hopes to develop a plan of work which will see a way to maximize the number of cells which can be genetically mutated. They recognize that patients with the mutated CCR5 genes may have an important input into the next phase.

The ‘functional cure’ is not around the corner but after longer and larger studies the treatment may become the next big advance against the HIV threat. Because the findings were only presented to a medical seminar and have not had a peer review they should be treated with caution.


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