Commentary: Transplants too Risky to Be a Cure for HIV | National News

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Twelve years have passed since the first patient, originally known as the Berlin Patient, was “cured” of HIV following a stem cell transplant to treat cancer. Now promising results for a second and third patient have been released to the public, begging the question: Is the third time a charm in the epic quest to cure HIV?

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Cases involving the second and possible third patients – known as the London Patient and the Dusseldorf Patient, respectively – were presented earlier this week at the Conference on Retroviruses and opportunistic Infections in Seattle. Each received a bone marrow transplant from donors with a rare genetic mutation. Since then, the London Patient has been HIV free while off of antiretrovirals for 18 months, and the Dusseldorf Patient has been virus free without use of antiretroviral medications for three months. Scientists can now link the genetic mutation in the donor to a possible cure for HIV, but the risks of bone marrow or stem cell transplantation may outweigh the benefits for those suffering from HIV.

Since the first reported cases in 1981, HIV/AIDS has become a global epidemic that has taken the lives of over 35 million people worldwide. As of 2017, the World Health Organization reported that there are approximately 36.9 million people across the globe living with HIV/AIDS. While scientists cannot still say the three patients have officially been “cured,” these cases show, at a minimum, rapid steps heading in the direction of long-term remission success for HIV patients.

At least two other patients have received the treatment and are still awaiting results, but it has failed in multiple other patients over the last 12 years, which may show that a bone-marrow transplant is not necessarily an option for eliminating HIV in all patients. As Dr. Joshua Mansour, a board-certified hematologist and oncologist who specializes in stem cell transplantation and cellular immunotherapy, explains, in the cases of the first two patients “a notable and vital factor to point out is that these patients underwent a stem cell transplant to treat their cancer (one of them leukemia and the other lymphoma). There are several dangerous and potential deadly risk factors with a hematopoietic stem cell transplant; including toxicity from preparative chemotherapy, acute and chronic graft-versus-host disease, and infection.”

Mansour also emphasizes that the donors used in stem cell transplants are very specific to each patient and matched accordingly, and these patients happened to be transplanted from a donor who had a rare mutation that blocks the virus’ infiltration of cells. “An important point to stress is that both of the patients were treated with stem cell transplants in which their donors carried a mutation that prevents expression of a known HIV receptor CCR5 (the most commonly used receptor by HIV-1).

But beyond the rarity of the mutation and the specificity of the three successful cases, the risks involved in a bone marrow stem cell transplant cannot be overlooked. HIV patients have poor immune systems which could lead to serious complications if the transplant were to fail. Researchers that have been following HIV patients with blood cancers who are receiving transplants report that about half have died from either the cancer or the effects of the transplant itself.

Bone marrow stem cell transplants involve using high-dose chemotherapy to essentially erase the already severely compromised bone marrow of an HIV patient before replacing it with donor cells, which produce new blood cells and help to grow new bone marrow in the patient. This allows the patient to generate a new immune system that may fight any cancer cells not killed by radiation or chemotherapy. It is believed that a common side effect of transplants, known as graft-versus-host disease, may be part of the mechanism behind the destruction of HIV in these particular patients.

Graft-versus-host disease triggers the donor cells to attack the existing cells of the receiving patient, destroying HIV infected cells. But if this is not in fact a contributing factor, treating patients with HIV this way could instead provoke a fatal condition, making transplantation an unrealistic and risky way of “curing” HIV infection. What does hold promise, however, is the possibility of taking a patient’s own stem cells and modifying them genetically to mimic the stem cells of those with the CCR5 mutation. That is what researchers should be aiming for.

To that end, research efforts are being led by IciStem, an international collaboration of a review panel comprised of European hematologists with an expertise in stem cell transplants, infectious disease specialists, virologists and immunologists with specific HIV expertise. While stem cell transplantation may not be the end-all of HIV for all of those afflicted, it continues to provide researchers with optimism and more information to lead them closer to a cure.



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