HIV Undetectable in 2 Men After Bone Marrow Transplants: Study

THURSDAY July 26, 2012 -- Following bone marrow transplants, two men infected with HIV no longer have any traces of the AIDS-causing virus in their lymphocytes, researchers report.

Lymphocytes are a type of white blood cell and are a key part of the immune system.

The U.S. researchers suspect that bone marrow transplantation along with continuation of antiretroviral therapy resulted in the dramatic effects evident eight months post-transplant. They are scheduled to present these preliminary findings Thursday at the International AIDS Conference in Washington, D.C.

HIV patients on antiretroviral therapy often achieve "undetectable viral loads," meaning there are no virus particles in their blood. But they still have latent HIV in their lymphocytes, and if antiretroviral therapy were discontinued, the latent HIV could reactivate.

But having no traces of HIV in these white blood cells is an indication that this "reservoir" of latent HIV may have been eliminated, the researchers believe.

At this point, they are far from saying these patients are cured. But the findings are "exciting," said Dr. Savita Pahwa, director of the Center for AIDS Research at the University of Miami Miller School of Medicine, who was not involved with the study.

"Every hint you get that it's possible to wipe out the reservoir needs to be investigated," she said.

"Eliminating the reservoir is the key to the cure," said Pahwa. She also stressed that it would only be possible to say these patients were "functionally cured" if the virus did not rebound when the patients went off antiretroviral therapy.

The two men whose cases are described in the paper underwent chemotherapy for blood cancers before receiving stem cell transplants. One had his transplant two years ago; the other, four years ago. Both also developed graft-versus-host disease (when transplanted cells attack the host cells) and continued with their antiretroviral medications throughout and after the transplant procedures.

Any of these factors could theoretically explain their HIV-free status, but the bone marrow transplantation combined with antiretroviral therapy seems the most likely explanation, said the study authors.

"We believe the transplanted cells killed off and replaced all of the patients' own lymphocytes, including the infected cells, and the donor cells were protected from becoming infected themselves by the antiretroviral therapy they were taking throughout the transplant period," said study senior author Dr. Daniel Kuritzkes, chief of infectious diseases at Brigham and Women's Hospital and professor of medicine at Harvard Medical School in Boston.

Graft-versus-host disease also probably played a role, he said. "The replacement of host cells by donor cells is itself a form of graft-versus-host reaction," Kuritzkes explained.

But the only way to verify that the transplant plus antiretroviral therapy can eradicate HIV is to take the patients off their medication regimens.

That would be the "next logical step," said Kuritzkes, adding that this would require patient consent and adherence to ethics protocols.

But even if the transplant procedure were found to eliminate the reservoir of latent HIV cells, bone marrow transplantation is a very risky procedure. Kuritzkes said he does not "foresee bone marrow transplantation being performed on otherwise healthy HIV-infected patients who are doing well on [antiretroviral therapy]."

Kuritzkes and his colleagues are continuing to enroll and follow HIV-positive patients who have undergone bone marrow transplants as part of a larger study.

This preliminary study contains echoes of the so-called "Berlin Patient," who has no detectable HIV cells in his blood five years after a stem cell transplant for leukemia.

Like the two men discussed in the current paper, the Berlin Patient -- Timothy Ray Brown of Seattle -- also had been diagnosed with HIV and also underwent chemotherapy (for acute myeloid leukemia) and developed graft-versus-host disease.

But, unlike the current patients, Brown received his stem cell transplant from a donor who had a rare genetic mutation that increases immunity against the most common form of HIV. He remained HIV-free after discontinuing antiretroviral therapy.

The two men described here received donor cells, which were "fully susceptible" to HIV, Kuritzkes said. This raises the possibility that a cure may be possible even when the donor does not have this gene mutation, he said.

Because this research has not been peer-reviewed and published in a medical journal, the data and conclusions should be considered preliminary.

More information

Visit the U.S. Centers for Disease Control and Prevention for more on HIV/AIDS.

Posted: July 2012


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