A First Step Toward a Cure for AIDS? Novel Procedure Appears to Have Eliminated HIV
November 5, 2008
We need a cure for AIDS. We can't treat our way out of this epidemic. Anti-HIV therapy is a lifelong commitment, accompanied by many life-altering and some potentially life-threatening side effects. And for every person placed on treatment, two to three are newly infected. In 2007 alone there were 2.7 million new infections, and only 31 percent of those who needed treatment received it. Viral reservoirs -- cells and tissues in which HIV remains dormant, beyond the reach of anti-HIV drugs but poised to grow at any moment -- persist for the life of an infected person. And while all currently available anti-HIV drugs suppress the virus, they cannot eliminate it.
Given this context, a brief report in February 2008 by a group of physicians from Germany appeared to change everything when presented as a poster at the annual Conference on Retroviruses and Opportunistic Infections in Boston. It described a 40-year-old man -- an American working in Berlin -- whose HIV had been under good control for several years using a typical cocktail of drugs known as HAART. Then he developed acute leukemia.
In an attempt to cure the leukemia, he underwent a course of radiation therapy and chemotherapy in preparation for a stem cell transplant. But in his case, rather than simply using the best match among available stem cell donors, his physicians did something very clever. They also screened potential donors for a natural mutation known as delta32 CCR5. CCR5 is the primary means by which most types of HIV infect cells. Individuals lacking this CCR5 receptor -- the 1.5 percent of the Caucasian population in America and Europe with the delta32 mutation -- are completely resistant to infection by the most common forms of HIV.
The patient's stem cell transplant was a success, although relapse of his leukemia required a second transplant using the same donor. Now off all anti-HIV drugs for almost two years, the patient continues to show no detectable signs of HIV in his blood, bone marrow, lymph nodes, intestines, or brain. To the limits of our ability to detect HIV, it appears that the virus has been eradicated from his body. At the very least this patient represents a functional cure: he is off all anti-HIV meds, has a normal T-cell count, and exhibits no evidence of virus.
amfAR quickly called together 10 experts in clinical AIDS, stem cell transplantation, and HIV virology for a two-day think tank at the MIT Endicott House to evaluate these data. The patient's physician, Gero Hutter, presented details of the case, which were closely scrutinized by all. In a summary statement, attendees indicated that this case does indeed represent at least a functional cure. Dr. Hutter agreed to ask his patient to provide additional blood samples so that scientists attending the amfAR meeting could perform even more sensitive tests to attempt to further document that the virus has been erased from the patient. amfAR is coordinating distribution of these samples.
But amfAR's involvement doesn't end there. It is possible that the patient may have been cured of HIV/AIDS. But the cost of such a stem-cell transplant procedure can run up to $250,000. It is associated with a relatively high death rate from infectious and immunologic complications, and the number of delta32-CCR5 donors of appropriate tissue type would be very small. Here further research may yield key answers.
For example, it is unknown whether the use of a delta32-CCR5 donor is essential. Perhaps the transplant procedure itself was the most important element. The potential to genetically engineer stem cells to remove CCR5 from a patient's own stem cells also exists, and strategies to do so were discussed at the think tank. These and related issues will serve as topics for an upcoming amfAR grant cycle.
Dr. Laurence is amfAR's senior scientific consultant.
This article was provided by amfAR, The Foundation for AIDS Research. Visit amfAR's website to find out more about their activities and publications.
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