Recent research at Oregon Health & Science University has brought scientists closer to developing a widespread cure for HIV, which has infected about 38 million people worldwide. Stem cell transplantation is among the methods being studied to treat HIV. This procedure, also known as bone marrow transplantation, is used to treat some forms of cancer. In 2009 the first known case of HIV being cured through a stem cell transplant was reported. The person living with HIV, known as the Berlin patient, was diagnosed with acute myeloid leukemia, a type of cancer, and underwent a stem cell transplant in Berlin, Germany. He received donated stem cells from someone with a mutated CCR5 gene, which normally codes for a receptor on the surface of white blood cells that HIV uses to infect new cells. This CCR5 mutation makes it difficult for the virus to infect cells, potentially making people resistant to HIV. Since the Berlin patient, four more people have been similarly cured.
The new study from Oregon Health & Science University shows that two nonhuman primates were cured of the monkey form of HIV after receiving a stem cell transplant. The study also revealed that two circumstances must co-exist for a cure to occur. This latest research adds to our knowledge about the mechanisms involved in curing HIV and would help to make an HIV cure work for anyone, and ideally through a single injection instead of a stem cell transplant.
The study was conducted on a species of nonhuman primate known as Mauritian cynomolgus macaques. All eight monkeys in the study had HIV, with half receiving stem cells from HIV-negative donors and the other half serving as the study’s controls and going without transplants. Of the four that received transplants, two were cured of HIV after successfully being treated for graft-versus-host disease, which is commonly associated with stem cell transplants. This highlights the power of linking human clinical studies with pre-clinical macaque experiments to answer questions that might be almost impossible to approach in other ways, as well as demonstrating a method to cure human disease.
The scientists involved in the study wanted to understand how stem cell transplantation worked to cure HIV. While evaluating samples from the subjects, the scientists discovered that two different, but equally important, ways the subjects beat HIV. First, the transplanted donor stem cells helped kill the recipients’ HIV-infected cells by recognizing them as foreign invaders and attacking them, similar to the process of graft-versus-leukemia that can cure people of cancer. Second, in the two subjects that were not cured, the virus managed to jump into the transplanted donor cells. In a subsequent experiment, the researchers verified that HIV was able to infect the donor cells while they were attacking HIV. This led the researchers to determine that stopping HIV from using the CCR5 receptor to infect donor cells is also needed for a cure to occur.
During the research, the scientists also discovered that HIV was cleared from the subjects’ bodies in a series of steps. First, HIV was no longer detectable in blood circulating in their arms and legs. Next, HIV couldn’t be identified in lymph nodes, or lumps of immune tissue that contain white blood cells and fight infection. Lymph nodes in the limbs were the first to be HIV-free, followed by lymph nodes in the abdomen. Identifying the step-wise progress of the disease elimination would help physicians evaluate the effectiveness of potential HIV cures. For example, examining the blood collected from both peripheral veins and lymph nodes could aid clinicians. This knowledge may also help explain why some patients who have received transplants initially appear to be cured, yet HIV is subsequently detected. The study hypothesizes that those patients may have had a small reservoir of HIV in their abdominal lymph nodes that enabled the virus to persist and spread again throughout the body.
The next phase of the research will see scientists digging deeper into the immune responses of the two nonhuman primates cured of HIV. They plan to identify all the specific immune cells involved, which specific cells or molecules were targeted by the immune system, and other characteristics.
This research is supported by the National Institutes of Health (grants AI112433, AI129703, P51 OD011092) and the Foundation for AIDS Research (grant 108832), and the Foundation for AIDS Immune Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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