began HIV treatment soon after. About 10 years later, in 2013, he was diagnosed with Hodgkin’s Lymphoma, stage IVb, an advanced stage of cancer that is sometimes seen in patients with HIV infection. Hodgkin’s Disease (Hodgkin’s Lymphoma) is oftentimes curable cancer, but in this case, the disease is diagnosed at an advanced stage. Treatment of this cancer requires multiple strategies, any of which could affect HIV disease. First of all, the treatment of cancer required a stem cell transplant (allogeneic stem transplant). Stem cells are the source of our infection-fighting cells in the body. Blood cells are collected from a matched donor and the stem cells are separated.
Then, radiation or chemotherapy is used to kill the cancerous blood cells in the patient and increase chances the donated cells will be accepted. The patient then receives the donated cells. It is most important to understand that the person who donated the cells to this patient had a genetic modification of a protein that HIV uses to infect cells. This protein is called CCR5 and the virus must attach to this protein on the outside of the cell in order to enter and infect the cell. Because of the altered structure of this protein, due to a genetic mutation present in about 1% of Europeans, the virus cannot attach and infect the lymphocyte. So now, this patient’s blood cells have been replaced with cells that are resistant to HIV infection. The HIV drug Maraviroc (Selzentry) essentially works the same way as this genetic mutation by blocking CCR5 and preventing HIV from infecting cells.
The treatment of the cancer also involved some courses with cancer chemotherapy before the donor cells are administered. The use of these cancer drugs may also have played an important role. Cancer chemotherapy can be toxic to blood cells. However, in this case, it could have possibly been helpful in eliminating cells harboring latent HIV virus, known as the reservoir (See article “Why we haven’t cured HIV Infection” January 4, 2019). Indeed when the researchers performed special tests to produce virus from the reservoir, no virus was produced; a good sign that the reservoir was eliminated. The transplant required immunosuppressive medicines to keep the patient from having a reaction and rejecting the transplanted blood cells.
So through the very complicated process of treating the London patient’s cancer, a “new” immune system was created by the stem cell transplant that is resistant to HIV, in a patient where it appears the reservoir was eliminated. About 14 months after the marrow transplant, the HIV medicines were stopped. The patient has been in remission from the cancer and has been off HIV medicines for over 18 months with no virus detected anywhere. In addition to not finding any virus hiding in the body, the patient has no antibodies to HIV, which further supports there is no virus hiding out in the body.
Many aspects of this case were seen in the Berlin patient, Timothy Brown. This patient was suppressed on HIV therapy for many years but then developed Acute Myelogenous Leukemia (AML) Treatment of this cancer also required stem cell transplantation. The patient also received cancer chemotherapy. When cancer returned several months later, a second transplant was needed and the patient received radiation therapy. The donor of the stem cells in both of the transplants for this patient was selected for the mutation to CCR5 that made his lymphocytes resistant to HIV infection. The leukemia was cured after the second treatment. This patient has been off HIV meds with no virus detectable in any part of the body for over 10 years.
Important similarities link these two cases. It is critically important that the stem cells they received came from donors with the mutation in the CCR5, protecting these cells from HIV infection. There are other aspects of these cases that probably relate to the outcomes, such as