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CATIE
Attempts at a cure

<p>Sean R. Hosein</p>


October 1, 2012

Several years ago, researchers in Berlin announced that they were able to cure an HIV-positive person of this infection. The cure required intensive bouts of chemotherapy and radiation, as well as stem cell transplants from a donor with a rare mutation conferring resistance to HIV infection. As a result, Timothy Brown, the patient who received these therapies, was very weak for several years and is now somewhat disabled, though he is cured of HIV. Other researchers have repeated the protocol used by the Berlin doctors but so far no one else has been cured and several patients have died.

For background information on these experiments, please see the following CATIE resources:

Researchers in Boston at the Dana-Farber Cancer Institute and Harvard University have been collaborating on another experiment aimed at repeating the success of the Berlin researchers without the grueling and highly dangerous chemotherapy and radiation exposure and also without using stem cell transplants from donors who can greatly resist HIV infection. Such donors have a rare mutation whereby a co-receptor needed by HIV is missing. Scientists call such a mutation “delta-32.”

Cancer

The research team enrolled two HIV-positive patients who were taking potent combination anti-HIV therapy (commonly called ART or HAART) and who had developed extensive cancers (lymphoma) of their immune systems; their chances of surviving these cancers were slim. Despite initial treatment with chemotherapy, the cancers had returned.

The men were treated with low-dose chemotherapy (not radiation) and were given stem cell transplants. These stem cells did not have any enhanced ability to resist HIV infection. In other words, they did not have the delta 32 mutation that the Berlin team used in its experiment. In addition, the Boston patients received immunosuppressive drugs - so-called transplant drugs - to allow the transplanted stem cells to survive attacks by the host immune system by partially weakening their immune system. These immunosuppressive drugs included the following:

  • prednisone
  • sirolimus
  • tacrolimus

Results

Nearly four years since their stem cell transplants the men are still alive. Moreover, HIV cannot be found in their blood samples or in cells of the immune system found in the blood. Levels of antibodies to HIV have greatly decreased.

It is important to note that the men remain on ART.

Researchers have not yet been able to extract small samples of lymph nodes or lymph tissue for analysis because the men are still relatively weak - both physically and immunologically - from all of the medical procedures they have undergone. So while HIV is absent from the blood, this virus may still be present in remote lymph nodes or tissues. The only way to confirm whether the men have been cured would be if they stopped taking ART and invasive procedures to extract samples of tissues from deep within their bodies were performed and such samples were analysed.

The Boston experiment, as well as other similar experiments being done by researchers in the U.S. and Western Europe, should be seen as works in progress. They will be closely watched for further developments. In the meantime, at least the two men in the Boston study have been cured of cancer.

These experiments with stem cell transplants and chemotherapy and subsequent transplant drugs are dangerous and will not be done on a large scale because among HIV-negative cancer patients such procedures carry a death rate of about 15%. No one is certain about the death rate for HIV-positive people, but it is likely to be at least as high.

- Sean R. Hosein

REFERENCE:

Henrich TJ, Sciaranghella G, Li JZ, et al. Long-term reduction in peripheral blood HIV-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation in two HIV-positive individuals. In: Program and abstracts of the XIX International AIDS Conference, 22–27 July 2012, Washington, DC. Abstract THAA0101.



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