Neil Canavan

July 09, 2013

KUALA LUMPUR, Malaysia — Two cancer patients with long-established HIV are infection-free after undergoing stem cell transplantation for their malignancies, and have no detectable viral load several weeks after stopping their antiretroviral medications.

The headline grabbing results, presented during a news conference here at the 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, are garnering international attention.

"I want to stress that longer-term follow-up is going to be needed to understand the full impact of stem cell transplantation with susceptible cells on viral persistence and reservoir ablation," Timothy Henrich, MD, from Brigham and Women's Hospital in Boston, told reporters. "It is possible that the virus could come back next week, or even next year."

Researchers are now considering the mechanism of viral clearance in patients undergoing allogeneic hematopoietic stem cell transplantation. Was it the medication's effect on the new immune cells, or was it the activity of the donor cells themselves?

Dr. Henrich and his team conducted a longitudinal assessment of several indicators of ongoing HIV infection. They quantified genomic HIV-1 DNA and viral coculture from purified CD4 T-lymphocytes and looked at HIV-1 DNA polymerase chain reaction of rectal tissue and residual donor peripheral blood mononuclear cells.

The researchers found that HIV-1 DNA from peripheral blood mononuclear cells was not detectable in either patient, indicating at least a 3 to 4 log10 decrease in peripheral viral reservoir size after transplantation.

I've never seen this much enthusiasm for the cure research agenda.

They detected no HIV-1 p24 antigen in viral coculture from purified CD4+ T-cells, and they found no HIV-1 DNA in rectal tissue, which is known to be a potential HIV reservoir. In addition, no HLA-specific or pooled HIV-1 peptides elicited a strong HIV-specific immune response in either patient.

As would be expected after a successful transplant procedure, residual host cells constituted less than 0.001% of peripheral blood mononuclear cells.

"Because of these findings, we felt justified in taking the patients off antiretroviral treatment," which had been maintained during and after transplantation, said Dr. Henrich. "It's an analytical treatment interruption. We want to stop therapy to see what happens." Does the virus come back? If so, how long does it take?

"Today, I am able to report that for 1 patient out to week 8 and for the other out to week 15, we continue to be unable to detect HIV RNA," he said. "No virus in peripheral blood, no virus integrated into cells, and no HIV DNA."

Dr. Henrich emphasized that stem cell transplantation is not a cure for AIDS. "This is not a practical strategy," he said. "Stem cell transplantation is dangerous; the mortality associated with the procedure is 20% or more. However, I think we can learn quite a bit from this type of study."

Toward a Cure

HIV clearance after bone marrow transplantation has been seen before. "I've been watching this, as we all have, for a number of years," said IAS president-elect Chris Beyrer, MD. "But we just couldn't talk about a cure, not for the longest time. Now the pace — the acceleration of data, the number of new reports, new approaches, the scientific energy and enthusiasm around this — really is dramatic. I think that's how you have to see these 2 cases."

Dr. Beyrer pointed out these patients are different from the highly publicized Berlin patient from a few years ago.

"The Berlin patient received stem cells from a donor who is one of a very small group of people who have a CCR5 delta 32 mutation, a genetic variance that enables resistance to HIV infection," he noted. In effect, "he got a new immune system that was resistant to infection."

The difference with the 2 new patients is that the stem cell donors had wild-type CCR5. If they were exposed to HIV, they would become infected like most people, Dr. Beyrer explained.

However, these 2 patients "do appear to be functionally cured; that's a huge advance."

The Berlin patient, the Mississippi baby, and the VISCONTI cohort all suggest that early treatment is key. There are likely more people out there who started treatment very early in the infection — particularly newborns — who are on lifelong therapy right now and might not need to be, he noted.

"It's really very exciting," Dr. Beyrer said. "I've never seen this much enthusiasm for the cure research agenda."

Dr. Henrich reports receiving financial support from the National Institutes of Health, Amfar, and the Bill and Melinda Gates Foundation. Dr. Beyrer has disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WELBA05. Presented July 3, 2013.


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