HIV 'gene hack' offers new treatment hope

“HIV gene therapy using GM cells hailed a success after trial,” reports The Guardian, while the BBC tells us that an “immune upgrade” could offer “HIV shielding”.

These headlines come following a small trial that examined whether it was safe to inject genetically modified white blood cells into people with HIV. This was achieved, but the study did not show whether HIV could actually be treated.

This was the first human trial for the technique and involved 12 people that already had HIV. They were all taking antiretroviral (anti-HIV) medication and had undetectable levels of the HIV virus in their blood. A type of white cell in their blood was genetically modified and then multiplied in the lab.

This genetic modification was done to imitate a rare, naturally occurring mutation, when two copies are present, which makes people highly resistant to HIV infection.

Researchers injected the modified blood cells into each of the 12 people with HIV. They did this to test the safeness of the treatment. There was only one serious transfusion reaction, with many of the participants experiencing milder reactions, which included fever, chills and bone pain.

The researchers also looked at the effectiveness of the genetically modified cells by asking six of the participants to stop their antiretroviral medication for 12 weeks – 4 weeks after the infusion. The researchers then looked at what happened to participants if they did not take their HIV medication for a few weeks, and what happened when they restarted it. The effects were variable in the six individuals.

This study provides some hope that genetically “edited” immune cells could be used to treat people with HIV, but it’s too soon to draw any strong conclusions as to whether it will be an effective treatment.

Where did the story come from?

The study was carried out by researchers from: the University of Pennsylvania; the Albert Einstein College of Medicine, Bronx; and Sangamo BioSciences, Richmond, California. It was funded by the National Institute of Allergy and Infectious Diseases; the Penn Center for AIDS research; and Sangamo BioSciences.

The study was published in peer-reviewed medical journal the New England Journal of Medicine.

The media reported the trial responsibly; however, there were a couple of inaccuracies.

The reduction in HIV viral level occurred after the levels had shot up when six participants stopped taking their antiretroviral medications. The HIV viral levels reached a peak six to eight weeks after the treatment was stopped, and then only gradually declined in the three participants who did not immediately restart medication, or already have one strand of their own DNA with the genetic mutation. This was not due to replication of the injected genetically modified T helper cells, as their numbers were steadily reducing.

What kind of research was this?

This was a phase one trial of a new potential treatment for HIV. It was non-randomised (the participants were specifically selected), and the participants and doctors were aware they were having the treatment. There was a selected group of people who were not given the treatment and acted as controls, but these people were not reported on in the journal article.

Phase one trials are the first ones carried out for a new treatment in humans. They are usually very small and are performed to test treatment safety. If successful, larger phase two trials and phase three trials are carried out to look further at safety and start to examine the effectiveness.

What did the research involve?

12 people with HIV infection were given genetically modified CD4 T cells. These a type of white blood cell and are often called “T helper cells”, as they send messages to other immune cells. The aim of the study was to assess the safety and side effects of the potential treatment, with a secondary aim of assessing the effect on the immune system and HIV resistance.

The genetic modification was performed to mimic a naturally occurring DNA mutation that some people have and is thought of affect around 1% of the population. This mutation, when present on both copies of a section of DNA, has been found to make them resistant to the most common strains of HIV. In people with HIV who have this mutation on one of the strands of DNA, the progression of their disease to AIDS is slower. There has also been one case of a person who had a stem cell transplant from a donor who had the mutation on both copies, and the HIV virus has been undetectable for them from more than four years without any antiviral therapy (the standard HIV treatment).

From this discovery, previous research on mice using genetically modified T helper cells showed that they functioned normally and were able to divide and multiply in response to usual stimuli. They were also protected from HIV infection and reduced the HIV RNA infection levels in the blood.

The main aim of this study was to assess the safety of the potential treatment in humans. The secondary aim was to assess the immune system and whether there was any HIV resistance.

12 people with HIV entered the study between May 2009 and July 2012. The inclusion criteria were that they were taking antiretroviral medication and were “aviraemic” (meaning that the level of HIV RNA was undetectable in their blood). The participants were split into two groups of six.

The participants gave a blood sample. From this, the T helper cells were genetically modified and multiplied. The cells were then injected back into their veins as an infusion. The infusion contained about 10 billion T helper cells, 11-28% of which had been genetically modified.

The participants were closely monitored for the first four weeks. The first group of six then stopped their antiretroviral treatment for 12 weeks. All participants were monitored for 36 weeks, and they are now in a 10-year follow-up study.

What were the basic results?

In terms of the primary aim of safety:

  • One participant suffered from a serious reaction. They had fever, chills, joint pain and back pain within 24 hours of the infusion, which was diagnosed as a transfusion reaction.
  • There were 82 mild and 48 moderate adverse events reported, but the researchers report that 71 of them were not related to the study drug.
  • The most common adverse event was a milder version of the transfusion reaction.
  • Garlic-like body odour was common and is due to the metabolism of a drug used in the process.

For the secondary aim of immunity to HIV:

  • In all 12 participants, the amount of T helper cell was significantly higher one week after the infusion (from 448 cells per cubic millimetre to 1,517) and 13.9% of them were genetically modified. It took on average 48 weeks for the cells to reduce by half, which suggests that the immune system did not reject them.
  • The genetically modified T helper cells went from the blood stream into the soft tissue, where the majority of this type of cell usually resides.
  • Virus levels became detectable in the blood of all six of the group who stopped treatment. Two of them restarted the antiretroviral treatment after eight weeks. The viral levels in three of the participants gradually reduced after a peak at eight weeks, before the antiretroviral treatment was restarted at 12 weeks. It then took 4-20 weeks for the viral levels to become undetectable.
  • The viral level in one of the patients who stopped antiretroviral treatment rose, but became undetectable before restarting treatment. It was found that he already had the genetic mutation in one strand of his DNA.

How did the researchers interpret the results?

The researchers concluded that genetically modified CD4 T-cell infusions are safe within the study's limits, but that the size of the study was too small to generalise this finding. The immune system did not reject the genetically modified T helper cells.


This phase one trial showed that the infusion of genetically modified T helper cells was achieved reasonably safely in 12 people with chronic HIV.

It isn’t clear if it could be an effective treatment for HIV, as the virus became detectable in the blood of all six participants who stopped taking their antiretroviral treatment. Although the levels of the virus then began to reduce after eight weeks, it only came back to undetectable levels in the person who already had one DNA strand of the genetic mutation. It took several weeks for this to happen in the other five people.

The primary aim of the study was to determine the safety of the treatment in humans, rather than to determine immunity to HIV. It may be that a different dose of cells is more effective. Further studies in larger numbers of people will now be needed to further examine the treatment’s safety and to look at its possible effectiveness and what factors and characteristics in a person might influence this.

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