HIV budding from a lymphocyte

Credit: CDC

MELBOURNE—Two men with hematologic malignancies who were also HIV-positive appear to be free of the virus after receiving stem cell transplants.

The patients have undetectable levels of HIV and remain free of their cancers—acute myeloid leukemia and non-Hodgkin lymphoma—more than 3 years after their transplants.

Importantly, the patients’ stem cell donors were not homozygous for CCR5-delta 32, a mutation that affords protection against HIV.

The researchers said these results herald a new direction in HIV research and provide hope for HIV-positive patients with leukemia and lymphoma.

The work was presented at the “Towards an HIV Cure Symposium,” which is part of the 20th International AIDS Conference.

Both patients were treated at St Vincent’s Hospital in partnership with the University of New South Wales’s Kirby Institute in Sydney, Australia.

One patient underwent a transplant in 2010 to treat his non-Hodgkin lymphoma, and his donor had 1 copy of CCR5-delta 32.

The second patient underwent a similar procedure for acute myeloid leukemia in 2011, and his donor did not have any copies of CCR5-delta 32.

Nevertheless, both patients were successfully cleared of HIV, although they remain on antiretroviral therapy as a protective measure.

“We’re so pleased that both patients are doing reasonably well years after the treatment for their cancers and remain free of both the original cancer and the HIV virus,” said David Cooper, MBBS, MD, DSc, of the Kirby Institute and St Vincent’s Hospital.

Until now, the only person considered to have cleared HIV is an American man, Timothy Ray Brown, who underwent 2 stem cell transplants in Berlin (in 2007 and 2008).

The cells in his second transplant included both copies of CCR5-delta 32, which affords protection against HIV and is found in less than 1% of the population. The man is no longer on antiretroviral therapy and remains free of HIV.

In Boston, 2 other patients underwent similar transplant s in 2012, but the donor cells did not contain CCR5-delta 32. In both cases, HIV returned after antiretroviral treatment was stopped.

“It is very difficult to find a match for bone marrow donors and even more so to find one that affords protective immunity against HIV,” Dr Cooper said.

While his group’s results are a significant development, the researchers stressed that transplants are not a general functional “cure” for the up to 38.8 million people infected with HIV worldwide.

“This is a terrific, unexpected result for people with malignancy and HIV,” said Sam Milliken, MBBS, of St Vincent’s Hospital. “It may well give us a whole new insight into HIV, using the principles of stem cell transplantation.”

“It is important to caution that, at this stage, this form of treatment is far too dangerous for treating patients with HIV alone, but there may be potential for using transplants as an effective treatment modality for HIV down the track.”

The researchers said the 2 Sydney patients will be the subject of investigations to determine where any residual virus might be hiding and how it can be controlled. And the patients’ results point to a new direction for HIV research.

“We still don’t know why these patients have undetectable viral loads,” said Kersten Koelsch, MD, of the Kirby Institute. “One theory is that the induction therapy helps to destroy the cells in which the virus is hiding and that any remaining infected cells are destroyed by the patient’s new immune system.”

“We need more research to establish why and how bone marrow transplantation clears the virus. We also want to explore the predictors of sustained viral clearance and how this might be able to be exploited without the need for bone marrow transplantation.”

For the time being, the results mean that more patients who are eligible for transplant might be able to participate in clinical trials to determine the value of this procedure in HIV.

Two blood cancer patients cleared of HIV