Men Became HIV Free After Bone Marrow Transplants

Two patients in whom HIV seemed to vanish after they were given bone marrow transplants to treat cancer remained free of the virus even after stopping treatment with HIV medicines.

The result yields growing hope that the virus could someday be cured, not just kept in check with a cocktail of medicines as it is now. The results of the study are being presented at a meeting of the International AIDS Society in Kuala Lumpur, Malaysia. Data on the same two patients was presented a year ago at a conference in Washington D.C. by the same researchers, Timothy Henrich and Daniel Kuritzkes.

But at the time the patients had not stopped taking their AIDS medicines. Bone marrow transplants are grueling and expensive procedures, and are not likely to be used for patients whose disease can be controlled with existing drug cocktails. But scientists hope that these cases could provide clues to new ways of trying to eradicate the virus from the body.

Both went to Brigham and Women’s Hospital in Boston for treatment for blood cancer, and eventually required that the stem cells in their bone marrow — which create the immune cells that fight disease and that are infected with the human immunodeficiency virus — be replaced as a treatment. Unlike most bone marrow transplant recipients, they did not ever stop taking their AIDS medicines to take chemotherapy.

Doctors have theorized that this kept HIV levels low enough that their new immune cells were never infected. Now the patients have stopped taking their AIDS drugs, one for 7 weeks and the other for 15 weeks. So far, the virus has not returned.

The researchers warn in two press releases and a scientific abstract that were made available to Forbes before publication that the patients cannot yet be said to be cured and that the virus might still come back. One man, Timothy Brown, an American treated in Berlin, is thought to have been cured by a stem cell transplant.

His transplanted bone marrow cells had a mutation in a gene called CCR5 that prevented the HIV virus from infecting them. It had been thought this might explain the cure, and that helped lead Sangamo, a U.S. biotechnology company, to develop an experimental gene therapy that tries to modify that gene.

The Brigham cases seem to indicate that a cure may not require a mutation in CCR5. “There was a sense that Timothy Brown’s immune system had been given an armor coating,” says Kevin Robert Frost, chief executive of amfAR: The Foundation for AIDS Research. But the new data suggest that changing CCR5 may not be the critical piece to clearing the HIV virus.

Tim Brown’s cure may have made him immune to HIV forever because it gave him immune cells with this mutation, though, while the two men treated at the Brigham could be infected again, Frost says.

He says that many companies are trying different techniques to try and cure HIV. In March, reports said that an infant may also have been cured of HIV by intensive treatment that began soon after infection. Together, these cases are leading to hope that one day HIV might be cured

. But researchers at the meeting warn that it could be many years before any such cure becomes available, if it ever does. “I don’t think anybody expects a single cure is going to work for everyone, at least not yet,” says Frost, the amfAR CEO. “We all see having a multiplicity of options as a very, very good thing.”

The studies at the Brigham were also supported by the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation. Update July 4, 2014: Edward Lanphier, President and CEO, Sangamo Biosciences, sent me the following statement: We read with interest your article on data presented at the meeting of the International AIDS Society earlier this week (“Hint to a Cure?: Two Men Remain HIV Free After Bone Marrow Transplants,” July 3, 2013).

The story notes the difference between the Brigham and Women’s approach used in these two patients. with the approach developed by Sangamo. The latter technique utilizes our zinc-finger nuclease (ZFN)-mediated genome editing technology to create the CCR5 mutation that essentially blocks HIV from infecting the immune system.

Many clinicians would agree, however, that the three possible treatment options described in the article—including that used in the two highlighted cases– are not practical in a treatment setting, or may present too many safety and tolerability risks for the vast majority of HIV-infected patients. Sangamo’s approach, now in a Phase Two clinical study, seeks to replicate the dramatic and enduring benefit seen both in the case of Timothy Brown (“The Berlin Patient”), and in many patients naturally resistant to HIV infection.

Additional Sangamo studies have found that the ZFN-based treatment creates a reservoir within the immune system of T-cells resistant to HIV infection. The ZFN-based therapy appears to be well- tolerated in patients studied to date, and may provide HIV-infected patients with a means of controlling the virus without further treatment. We await completion of our ongoing clinical studies later this year.


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