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Cure Attempted in HIV-Positive Boy

, by Reilly O'Neal

[Update, July 2013: Eric Blue, the young man who underwent this pioneering procedure, has died from complications related to his stem cell transplant. Our hearts go out to his family.]

This week a 12-year-old boy born with HIV underwent a stem cell transplant—with cells carrying an HIV-blocking genetic variation—to cure both his leukemia and his HIV. Three months from now, his medical team at the University of Minnesota hopes to declare their patient cured.

Déjà Vu?

If this sounds familiar, that’s because it is similar to the experience of “Berlin Patient” Timothy Brown, the first person known to be cured of HIV. Following a diagnosis of acute myeloid leukemia, a type of blood cancer, Brown had aggressive chemotherapy and radiation and received stem cells taken from the bone marrow of a donor with a unique genetic mutation called CCR5-delta-32.

This mutation disables the CCR5 receptor, one of the entry points that HIV uses to infect immune system cells. An estimated 1% of people of European ancestry carry the mutation, which confers virtual immunity to HIV. The combination of chemo, radiation, and transplantation of stem cells with this genetic variant essentially regrew an HIV-uninfected immune system for Brown, who remains off antiretroviral drugs and free of functional virus years later. (Hear the remarkable story from Brown himself.)

Why isn’t everyone with HIV getting the same treatment? For one, the chemotherapy and radiation are themselves extremely harsh and even potentially deadly, killing off not only the cancerous blood cells but also the patient’s bone marrow cells, and rendering the individual vulnerable to other infections. (Indeed, Brown himself recounts that he underwent these treatments only as a last resort for his leukemia.)

For another, transplant recipients like Brown must be matched with a genetically compatible bone marrow donor if the transplanted stem cells are to successfully prompt production of healthy new blood cells within the recipient’s own bone marrow. This “tissue typing” means that finding a match is a challenge in its own right, even without the added difficulty of identifying a CCR5-negative donor.

A New Approach

To get around this problem, the University of Minnesota team took a different tack—one they hope will not only cure their patient but also ultimately yield a more practical, safe, and widely available option for curing HIV.

Rather than searching high and low for a compatible bone marrow donor with the CCR5-delta-32 mutation, they found their HIV-resistant cells right on the shelf: in umbilical cord blood—that is, leftover blood taken from placentas after birth and stored for research and medical needs.

Cord blood “is a little bit more forgiving in terms of allowing mismatches with that tissue typing,” explained Michael Verneris, MD, the boy’s blood and marrow transplant physician, in an interview with Minnesota Public Radio. “That allowed us to actually find a donor that had this resistance that could be used to treat his HIV, hopefully, as well as his leukemia.”

How’s the patient? Tuesday’s transplant went off without a hitch and the young man is doing remarkably well, his doctors report. “After having had three days of chemotherapy and four days of total body irradiation, many patients at this particular point would be feeling quite ill,” said pediatric hematologist/oncologist John Wagner, MD, in the same radio interview. “Not our patient….The infusion of these cord-blood stem cells went without any complications, and he looked great.”

Next Steps—And an Eye to the Future

The next several months will bring close monitoring and regular testing; if the young man’s leukemia is going to recur, his doctors explained, it will most likely do so within the first two years after the transplant.

“As far as the HIV goes, that’s a very different story,” added Verneris. “Our plan right now is to continue him on his [antiretroviral] medications, and then, as his new bone marrow starts working and repopulating a new immune system, we plan on removing those drugs somewhere around three months from now.”

Wagner and Verneris are confident that, by that time, they will know whether the transplant was successful in eradicating HIV: “We expect that we won’t be able to detect it” with viral load tests and highly sensitive assays.

As exciting as that “proof of concept” would be, the scientific community will demand longer-term follow-up, the physicians acknowledged. “Even for Timothy Brown,” said Wagner, “they continue to test him now five, six years later just to verify that, yes indeed, this is never going to come back. So it will be ongoing.”

Should the cord-blood stem cell transplant prove effective for curing HIV, it will represent a tremendous breakthrough in the quest for a cure. “To be able to find a bone marrow donor is just so unlikely for the majority of patients that it becomes really not a very practical approach,” explained Wagner. “Cord blood, on the other hand, is much more practical. It’s on the shelf, it’s in the bank—all we need to do now is type all of those for this CCR5 variant, this HIV-resistant variant, because then we can make this [procedure] readily available to all those people who are waiting.”

Given the harshness of the chemo and radiation used in both Timothy Brown’s cure and this young man’s treatment, Wagner added, “really the next step is also to figure out, how do we make this a safer therapy?”

It’s early days yet for this novel approach to an HIV cure. Keep an eye on BETA for more news on this and other developments in HIV cure research.

Reilly O’Neal is a freelance writer and former editor of BETA.

Selected Sources

Hutter, G. and others. Long-term control of HIV by CCR5 delta32/delta32 stem-cell transplantation. New England Journal of Medicine 360:692–98. February 12, 2009.

Minnesota Public Radio. U doctors’ historic effort to cure child with HIV and leukemia. April 24, 2013.

University of Minnesota. U of M researchers conduct world’s first cord blood transplant aimed at curing Leukemia and HIV/AIDS. Media release. April 23, 2013.

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