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Cure from HIV Infection

So far the only person believed to have been cured from HIV infection is Timothy Brown, after receiving a number of anti-cancer treatments and eventually a stem cell transplant to treat acute myeloid leukemia. The stem cells came from a donor who was homozygous for the so-called CCR5Δ32 allele, which abrogates expression of the HIV co-receptor CCR5 on cells (see In Pursuit of a Cure, IAVI Report, Jan.-Feb. 2012).

It’s still unclear exactly what part of Brown’s complex therapy cured him and if this kind of cure can also be achieved in other patients, which is why researchers are interested in reproducing the result. Today, John Mellors from the University of Pittsburgh reported on attempts to do so. Mellors said that Brown received a so-called allogeneic stem cell transplant, which means that the stem cells came from a different person. Mellors said this has the advantage that the donor cells recognize the remaining recipient cells as foreign and kill them, making it more likely that the donor cells fully replace what remains of the recipient’s immune cells after most of them were removed by irradiation. However, there is also a chance that the recipient’s cells reject and kill the donor cells, in which case the patient dies of leukemia. This is part of the reason why an allogeneic stem cell transplant has a 25% mortality rate, Mellors said.

Because the mortality is so high, Mellors said, researchers tried a less risky variation of the treatment Brown received: They treated HIV-infected people who needed a transplant with an autologous stem cell transplant, which uses cells that are taken from the patient’s own body. While this approach has a much lower mortality of 5%, it also has the disadvantage that some of the transplanted cells likely carry integrated HIV DNA, because they come from the HIV infected recipient’s own body. “You can’t sort cells for latent HIV,” Mellors said, adding that this is probably one of the reasons why this approach did not cure any of 10 HIV-infected patients where it has been tried.

Therefore, researchers are currently enrolling HIV-infected patients who need a transplant into a 15-persontrial that will treat them with allogeneic transplants, the treatment Timothy Brown received. Like in Brown’s case, researchers will also try to find donors that are homozygous for the CCR5Δ32 allele.

If this results in a cure at least in some cases, it will be a proof of principle that a cure from HIV can also be achieved in other patients, and will shed light on why Brown was cured. But even then, the approach will never become a treatment because of the high mortality rate associated with it, Mellors said. “It’s just proof of principle, that’s all,” Mellors said. “It’s got no practical significance whatsoever.”