The ‘Cure’ was NOT So Easy
attached is pdf of abstract from CROI 2008 conference.
You may have read a few days ago the story of a 40-year old HIV+ German man who had leukemia who received a bone marrow transplant and now they can’t find HIV in him 600 days after the procedure. Well, this positive sounding headlines don’t tell the whole story of what the patient had to go through. So here is some additional information and a link to the poster explaining more details.
Apparently, the patient had bad case of acute myeloid leukemia, was unresponsive to standard leukemia, so he had to get a bone marrow transplant. He had been undetectable (HIV viral load) for a long time on HAART. The German doctor found a matched donor who was CCR5 delta 32. they gave the German man ablative chemotherapy (tried to kill all the patient’s cells) while on ART, then transplant delta 32 cells. ART was stopped. Now 600 days off ART there is no evidence of HIV, by standrad PCR and some other tests (DNA PCR, and HIV from PBMCs also negative).
Leukemia is still not totally gone, the patient is still cytopenic; unsure but he may still e getting chemo once in a while. There is graft vs host and graft vs tumor: that is the donor CCR5 delta 32 recognize any remaining patient cells as foreign and try to kill them whether or not these patient cells are normal or cancerous….this is the desired outcome in marrow transplant for cancer, and how it would clear cancer.
So, the results show a ‘functional cure’, but it seems that most people would not want to go through al this and you would have to find a matched donor who was CCR5 delta 32.
A number of researchers think there still is HIV remaining somewhere in this patients body but hasn’t yet been found or surfaced. Of course this would be in line with the thinking that HIV reservoirs exist and they cannot be purged.
Here is Wall Street Journal article
ovember 7, 2008, 8:35 am
Did a Bone Marrow Transplant Cure a Cancer Patient of AIDS?
Posted by Jacob Goldstein
A 42-year-old man who had both leukemia and AIDS received a bone marrow transplant — a common, late-stage treatment for that type of cancer. His doctor selected a bone marrow donor who had a rare genetic mutation that renders people virtually immune to HIV. The transplant appeared to cure the patient of AIDS.
We’re as wary as the next guy of inferring too much from a single case study. Maybe it was a fluke; maybe there were unknown factors at work. But this one is pretty intriguing.
The case was presented at a conference earlier this year (here’s the abstract), and written up in this morning’s WSJ.
As is common for bone marrow transplant recipients, the patient first had radiation and chemotherapy, which tends to kill off many of the immune cells that harbor HIV. After the transplant, the patient’s immune system was repopulated by cells created by the donor marrow.
The donor had a mutation, present in about 1% of Europeans, that creates immune system cells that lack a receptor molecule called CCR5. That receptor plays an important role in HIV’s ability to enter the cell. (Pfizer’s HIV drug Selzentry works by blocking CCR5.)
So the patient’s immune system was repopulated with immune cells that carried the mutation. And, nearly two years after undergoing the transplant, he shows no signs of having any HIV left in his body — despite the fact that he hasn’t taken any AIDS drugs since before the transplant.
Perhaps the most important caveat is just how risky bone marrow transplantation is: It’s given to cancer patients after other treatments fail, and it kills up to 30% of patients.
But researchers hope to apply the apparent lessons of this case to strategies using gene therapy (which carries its own risks) to try to induce the protective mutation in patients with HIV.
David Baltimore, who won a Nobel Prize for research on tumor viruses, has started a company to use gene therapy to target HIV. He calls this case “a very good sign” and a virtual “proof of principle” for gene-therapy approaches.
Image of HIV by C. Goldsmith via CDC