Two men cleared of AIDS virus after bone marrow transplants

Two previously HIV-positive Australian men have shown no signs of the AIDS virus for more than three years after receiving bone marrow transplants.

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HIV on macrophage image by Public Library of Science

A 53-year-old and a 47-year-old man appear to be clear of HIV after receiving bone marrow transplants for leukaemia and lymphoma respectively at St Vincent's Hospital in Sydney, Australia, in partnership with the University of New South Wales' Kirby Institute.

Moreover, the leukaemia patient is the first recorded case of clearing the virus without the presence of a rare anti-HIV gene in the donor marrow.

To date, there have been several reported cases of cleared HIV. Timothy Ray Brown, a US citizen, was treated in 2007 and 2008 for leukaemia with transplanted stem cells from a donor with the CCR5 delta32 mutation, which is resistant to HIV, and was reported clear of the virus in 2008. Brown stopped taking his antiretroviral medication and has remained HIV-free.

In 2012, two other patients in Boston had similar treatments with bone marrow cells that did not contain the mutation. They initially tested clear of the virus, but -- when they ceased taking antiretroviral medication -- the virus returned.

The lymphoma patient, treated in 2010, did receive one transplant of bone marrow that contained one of two copies of a gene that is possibly resistant to HIV. The leukaemia patient, treated in 2011, received donor marrow with no resistive gene. Both patients remain on antiretroviral medication as a precaution, since the virus may be in remission rather than completely cured.

"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 study senior author and UNSW Kirby Institute director Scientia Professor David Cooper said.

The next step is to figure out why the body responds to a bone marrow transplant in a way that makes the virus retreat. One possible explanation is that the body's immune response to the foreign cells of the transplant causes it to fight harder against HIV. This is because, while bone marrow transplant seems to be the most effective means of clearing the AIDS virus to date, it is not an acceptable risk for patients whose lives aren't already endangered by bone cancer.

"The procedure itself has an up to 10 percent mortality rate," Professor Cooper explained. "But you take that risk in someone with leukaemia or lymphoma because they're going to die without it, and the transplantation will result in cure. For someone with HIV, you would certainly not transplant them when they have an almost normal life span with standard antiretroviral therapy."

The team of researchers plans to replicate the immune response to bone marrow transplantation in a laboratory setting in the hope of devising a less invasive and less dangerous immunotherapy against the virus.

They will also be studying the two patients to help figure out where in the body the virus is hiding.

"Working out where the remains of the virus is hiding has become the big scientific question in the HIV/AIDS research community. It will be essential to understand in order to achieve a cure," Professor Cooper said.

"We still don't know why these patients have undetectable viral loads. 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," the study's first author, Doctor Kersten Koelsch of the Kirby Institute, added.

"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."

The team will be presenting their research 19 July 2014 at the 20th International AIDS Conference in Melbourne, Australia.

 

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