Timothy Ray Brown has officially been declared cured of HIV. A US citizen living in Germany with HIV, Brown was treated for leukemia in 2007 at the Charite University of Medicine in Berlin. As part of his treatment, he received stem cell transplants from a donor with a naturally occurring genetic resistance to HIV. In February of 2009, his doctors published a report in the New England Journal of Medicine detailing the apparent absence of the HIV virus in his system after being treated for leukemia. Now, in the medical journal Blood, those doctors have described the even more rigorous examination of his body, including looking at brain and spinal samples, that they performed to demonstrate that Brown no longer has HIV. The virus isn’t simply in regression, it’s gone. While the exact methods used to remove HIV from Brown will likely prove too severe to see use in other patients, his cure raises the possibility of new avenues of attack against the disease. Should this case raise our hopes about a universal cure for HIV/AIDS? Yes, but with some big caveats.
Brown’s path to a cure was not for the faint of heart. I discussed part of his case history in my coverage of his condition in the beginning of this year, but it’s remarkable enough to bear repeating. Having contracted HIV in the ’90s, Brown was being successfully treated using anti-retroviral drugs (HAART) but developed acute myeloid leukemia in 2006. To treat the cancer, Brown was subjected to three rounds of chemotherapy, drastically impairing his immune system. It also induced renal failure, and so his HAART treatments had to end. Predictably, the levels of HIV in his system spiked. After three months he was able to resume standard HIV therapy and his levels dropped again. That’s when the cancer returned stronger than ever. With his infected immune system nearly destroyed, he was ready to have it augmented by someone else’s. Brown received bone marrow stem cell transplants from a donor, a process that carried a significant risk of death (about one in three don’t survive) but that would allow the donor’s immune system cells to grow inside him. A year after this dangerous procedure he had to go through it again. Despite all these opportunities for disaster, Brown survived.
More than that, his HIV was gone. Brown’s stem cell donor had been selected because he possessed a genetic variation that causes a receptor (CCR5) to be missing from his cells. This variation occurs in around 1% of people of Caucasian descent and has been known to confer a strong resistance to select strains of HIV by interfering with the way the virus enters human cells. It’s thought that the damage to his immune system, followed by the stem cell transplant, caused all traces of HIV to be removed from Brown’s body. Chemo killed off infected cells and the new resistant cells kept the virus from rebounding.
All this came at a price, however. Brown has been on immuno-suppressive drugs for 38 months. Following his transplant (17 months) he developed a neurological condition that required a brain biopsy and sampling of cerebrospinal fluid. According to AIDSMap, that neurological condition led to injury including temporary blindness, and Brown is still undergoing physiological and speech therapy to help him recover.
During his long recovery, doctors continually took samples of his immune system, measured the level of HIV antibodies, and examined the biopsied brain sample. Every indicator showed that Brown’s immune system was not only being populated by the donor cells, but that the viral load in his body was apparently zero. In Blood, the doctors at Charite University of Medicine point out that the donor cells are still susceptible to certain strains of HIV. In fact, Brown had those strains! Despite this remaining susceptibility, the virus never rebounded. It looks to have been completely cleared. As I said when discussing Brown earlier this year, the complete removal of HIV with stem cells containing a genetic variant that shouldn’t have provided him universal protection is very curious. It shows that there is still much to learn about genetic resistance to the virus.
Brown’s own clinical history has proven harsh, but his ongoing legacy is going to provide some remarkable hope to HIV patients everywhere. Will we subject patients to multiple rounds of chemotherapy followed by stem cell transplants from special donors with faulty CCR5 receptors? I certainly hope not, especially considering how effective HAART can be when managing HIV/AIDS. Repeating Brown’s ordeal would be unnecessarily risky for patients. One in three would likely die! Yet there are parts of his treatment that could be pursued. According to AIDSMap, doctors have explored the possibility of collecting large stores of stem cells from donors with the right kind of CCR5-based resistance. Researchers are also performing clinical trials to study ways in which the CCR5 receptor could be knocked out of cells using gene therapy. Why receive a transplant when you can just teach your cells to bar their doors against HIV?
Genetic therapies may prove to be a possible cure for HIV/AIDS. There are, in fact, multiple targets for such treatments. We recently discussed how variations in the HLA-B protein and gene can also provide protection against the disease. It will take several years to understand and perfect such roadblocks that we can use to stop the spread of HIV in the body. While gene therapies are promising avenues of research, and are reinforced in theory by Brown’s case history, such cures won’t be around for a while.
That long-term hope without short-term payoff is how I would characterize this case in general. The power of the CCR5 variation and its ability to be transferred to others through stem cell transplant is remarkable. Yet while we may see Brown’s treatment repeated, it is simply not a practical therapy for most HIV patients. Eventually, however, we’ll have enough genetic targets, and enough experience hitting them, that we’ll be able to “upgrade” the immune systems of the HIV infected with minimal risk to their lives. With any luck, such treatments will be cheap enough that they can be provided to people all over the world. Who knows, maybe we’ll even find a way to provide such ‘natural’ resistance as a preventative measure. Brown’s heroic journey through chemotherapy and stem cell transplants, his defeat of cancer and HIV, and his living proof that a cure is possible, make for a momentous occasion. It should give us hope, but it will also demand patience.
[image credit: Peter Rigaud]
[sources: Hutter et al 2009, NEJM; Allers et al 2010, Blood; AIDSMap]
