A setback for potential HIV therapies
Via the Boston Globe, and repeated extensively on the Internet, a sobering update on the future of a potential AIDS treatment. The only successful “cure” of HIV infection has been the Berlin patient, who after 12 years of being HIV positive developed acute myeloid leukemia in 2007. The treatment for the leukemia was irradiation followed by bone-marrow transplant. The bone marrow cells received by this patient were free of HIV, and turned out to have a mutation in the CCR5 gene which enabled the donated cells to be naturally resistant to HIV infection. The naturally occurring CCR5-delta32 mutation is found in human populations, and the wild type version of the gene acts as a co-receptor for HIV attachment during the infection process. Cells possessing the mutated version of CCR5 resist viral infection, simply because the mutant version prevents the virus from attaching in the first place. The Berlin patient recovered from his bone marrow transplant after some complications, however he remains cancer free, and is currently considered HIV free as well due to the inability to detect any virus in his system.
Since the approach shows promise, additional limited human trials have been conducted in the interim. A study at Brigham and Women’s Hospital in Boston also administered donor bone marrow to two HIV positive patients who had also been diagnosed with lymphoma. Unlike the Berlin patient, these new patients did not receive donor bone marrow from the HIV-resistant CCR5-delta32 cells, but instead received wild type CCR5 donor cells. The thought was that the combination of radiation to existing blood stem cells plus aggressive anti-viral therapy would eliminate all existing reservoirs of the virus, again effecting a cure for HIV infection. For months after the transplant, the patients maintained undetectable levels of virus while on antiviral medication, prompting researchers to see if they would remain virus-free when the antivirals were removed. The two patients agreed earlier this year to stop their medications, and doctors carefully monitored their blood for presence of the virus. Preliminary results announced this summer suggested that both patients remained virus free for two to three months after stopping the antivirals.
The current news alert however reports that both of the patients have in the interim again shown detectable levels of the virus, leading their doctors to recommend resuming the antiviral medication regimen. The discouraging report reinforces that the ability of HIV to become latent in cells will continue to be a significant challenge in the path to develop a cure. The researchers at Brigham and Women’s Hospital are currently reviewing data from the two patients to see if they can potentially identify where virus remained hidden in their bodies, and to determine why the patients did remain essentially virus-free for an extended period of time without antiviral medications. One significant question they are looking at is one of timing; does the period between the bone marrow donation and when the antiviral medications are halted play a role in the ultimate outcome. Further trials are planned.