Supercharging Immune Cells May Help Control HIV Long-Term

A Miracle cancer therapy that involves engineering a patient’s own immune cells is being repurposed for HIV, and early results from two individuals hint at its promise for long-term control of the virus. As part of a clinical trial, scientists took people’s own immune cells and reprogrammed them in a lab to recognize and attack HIV in the body. After a single infusion of the modified cells, two individuals with HIV now have undetectable levels of the virus—one for nearly two years and the other for almost a year. Both have been able to go off HIV medications entirely. The two people are part of a small study to test the treatment’s safety and feasibility. The initial findings were announced last week at the of American Society of Gene and Cell Therapy annual meeting in Boston. “These are early days. If we can provide the proof-of-concept that this approach is both safe and effective, then there are lots of ways in which it can be optimized, to make it more affordable and scalable,” says Steven Deeks, a professor of medicine and HIV expert at the University of California, San Francisco, who led the trial. The technique, known as CAR-T cell therapy, has been used in tens of thousands of patients with tough-to-treat cancers. Half a dozen or so drugs have been approved that rely on the technique. The treatment essentially supercharges a person’s immune system to directly attack and eliminate cancer cells. Recently, it’s also been used successfully to treat severe autoimmune diseases. “This is pretty exciting,” says Andrea Gramatica, vice president of research at amfAR, the Foundation for AIDS Research, who was not involved in the trial. “The reason this study matters and is particularly important is because it gives the HIV field a real, clinical clue that teaching the immune system to control the virus without antiretroviral therapy is achievable.” Scientists have been pursuing a cure for HIV since the virus was first identified in the early 1980s. Antiretroviral therapy prevents the progression to AIDS by suppressing the virus to undetectable levels, but people must take medication for the rest of their lives. It has transformed HIV into a chronic condition that allows people to have a near-normal life expectancy. Yet not everyone who is HIV positive is aware of their status, and in some rural and low-income parts of the world these medications are still not widely accessible or affordable. Up until now, there are under a dozen documented cases of sustained remission from HIV—known as a “functional cure” because the virus is still present in the body but is suppressed to levels that are undetectable by the immune system and HIV medication is no longer needed. Each of those individuals developed cancer and underwent stem cell transplantations as part of their treatment. In all but one of those cases, doctors used stem cells from donors with a rare genetic mutation called CCR5 that naturally prevents HIV from entering and infecting healthy cells. Timothy Ray Brown, known as the “Berlin patient,” was the first known person to be cured of HIV in this way in 2008. The examples of sustained remission “have taught us that the immune system can, under the right conditions, clear HIV,” says Boro Dropulić, executive director of the Maryland nonprofit Caring Cross, who developed the CAR-T therapy for HIV. But stem cell transplants aren’t scalable, he says. They’re intensive procedures that carry serious risks such as graft-versus-host disease, when the transplanted cells recognize the recipient’s cells as foreign and attack them. “What we're trying to do is to engineer that outcome deliberately without requiring cancer, without requiring a specific donor,” Dropulić says. His organization is working on making advanced therapies like CAR-T more accessible and affordable.