Yet another rash of stories touting a putative HIV/AIDS cure has gripped the media. This one involves a man with both leukemia and HIV, who received a specially engineered stem cell transplant aimed at both treating his cancer and making his new blood cells resistant to HIV infection. As the Wall Street Journal first reported on 8 November, for nearly 2 years, the man has not taken anti-HIV drugs, and his doctors have not found the virus in his blood.
The basic science behind the transplant makes good sense. The man, an American living in Germany, was given chemotherapy and radiation to ablate his blood cells at Charité Hospital in Berlin. Then, he received a bone marrow transplant of stem cells from a person who naturally had a genetic mutation that disrupts a protein called the CCR5 receptor. HIV uses this receptor to enter cells, and they become resistant to HIV infection when it's crippled. Several gene-therapy studies are under way that exploit similar strategies (Science, 3 August 2007, p. 612).
As with every previous cure story, however, this one has a long list of caveats. A true cure, for example, would mean that an infected person has become virus-free. But, as the man's doctor, Gero Hütter, acknowledged at a recent meeting on viral persistence and eradication held by the American Foundation for AIDS Research (amfAR), low levels of HIV can escape detection by all but the most sensitive tests, and these tests have not yet been done on the patient's blood. Every time "cured" people's blood has been examined with these techniques in the past, researchers have found the virus. Indeed, participants at the amfAR meeting agreed to dub the man only "functionally" cured: It's possible, if not likely, that he harbors the virus in tiny quantities in cells that were not ablated before his transplant.
Other caveats further underscore the limitations of this advance. Ablating a person's bone marrow and then transfusing them with another's cells is a high-risk procedure, leading to death in up to one-third of patients. Hütter stressed this at a press conference in Berlin on 12 November. "The therapy has such a high mortality rate that it can't be justified ethically other than in this special situation where the patient has to have a transplant due to another illness," he said. "I say this in order to reduce false hopes."
The procedure also costs somewhere in the neighborhood of $250,000, which puts it out of reach for most HIV-infected people in the world. Finally, the American apparently still faces serious health problems, and HIV, if it is still in his body, may well find a way into his fortified blood cells: People who naturally have mutated CCR5 genes and thus no functioning receptor have become infected when HIV exploits a related cellular receptor.
The bottom line is that resistance does not equal full protection, says Mario Stevenson, who studies how HIV causes disease at the University of Massachusetts, Worcester. "It's a proof of concept for gene therapy, but it's not a cure."
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