Man unexpectedly cured of HIV after stem cell transplant

The man became the seventh person to remain HIV-free after receiving a stem cell transplant to treat blood cancer. Notably, he is also the second of seven people to receive stem cells that were not actually resistant to the virus, suggesting that HIV-resistant cells may not be needed to treat HIV.

“The fact that cure is possible without this resistance gives us more options for treating HIV,” says Christian Gebler at the Free University of Berlin.

Previously, five people became them HIV free after receiving stem cells from donors who had a mutation in both copies of the gene encoding the CCR5 protein, which HIV uses to infect immune cells. This led scientists to conclude that having two copies of the mutation that completely removes CCR5 from immune cells is critical for treating HIV. “The use of these HIV-resistant stem cells was thought to be necessary,” says Gebler.

But last year a sixth man, known as the “Geneva patient”, was declared free of virus for more than two years after obtaining stem cells without the CCR5 mutation, suggesting that CCR5 is not the whole story. Although many scientists believe that the roughly two-year period without the virus is not long enough to prove that they are truly cured, Gebler says.

The latest case supports the idea that the Geneva patient has recovered. It tells the story of a man who received stem cells in October 2015 to treat leukemia, a type of blood cancer in which immune cells grow out of control. The man, who was 51 years old at the time, had HIV. During treatment, he received chemotherapy aimed at destroying the vast majority of his immune cells, making way for donor stem cells to create a healthy immune system.

Ideally, the man would have received stem cells resistant to HIV, but they were not available, so doctors used cells carrying one typical and one mutated copy of the CCR5 gene. At the time, the man was taking standard HIV treatment called antiretroviral therapy (ART), a combination of drugs that suppress the virus to undetectable levels, meaning it can't be passed on to other people and reducing the risk of infection of donor cells.

But about three years after the transplant, he decided to stop taking ART. “He felt like he waited a while after the stem cell transplant, his cancer was in remission, and he always felt like the transplant would work,” Gebler says.

Soon after, the team found no evidence of the virus in the man's blood samples. Since then, he has remained free of the virus for seven years and three months, which was long enough for him to be considered “cured.” No HIV was found in his body for the second longest period of seven people declared free of the virus, with the longest case being HIV free for about 12 years. “It's amazing that 10 years ago his chances of dying from cancer were extremely high, and now he has overcome this fatal diagnosis of a persistent viral infection, and he is not taking any medications – he is healthy,” says Gebler.

This discovery revolutionizes our understanding of what is needed to treat HIV using this approach. “We thought you needed a transplant from donors who don't have CCR5, but it turns out that's not the case,” says Ravindra Gupta from the University of Cambridge, who was not involved in the study.

Scientists generally believed that such treatment relied on the fact that any virus lurking in the recipient's remaining immune cells (after chemotherapy) could not infect donor cells, meaning that it could not replicate. “Essentially, the pool of host cells for infection is drying up,” Gebler says.

But the latest case suggests that a cure could be achieved instead if non-resistant donor cells are able to destroy any of the patient's remaining original immune cells before the virus can spread to them, Gebler suggests. These immune responses are often caused by differences in the proteins present in the two sets of cells. According to Gebler, this causes donor cells to recognize residual recipient cells as a threat that needs to be eliminated.

The results show that a broader pool of stem cell transplants than we thought, including transplants without two copies of the CCR5 mutation, could potentially cure HIV, Gebler says.

But it is likely that for this to work, many factors, such as the genetics of the recipient and the donor, must match, so that, for example, the donor's cells can quickly destroy the recipient's cells. What's more, in the latter case, the man carried one copy of the CCR5 mutation, which could change the distribution of his immune cells throughout the body in a way that could make it easier to treat him from the virus, Gebler says.

This means that most people receiving stem cell transplants for HIV and blood cancers should be offered HIV-resistant stem cells if possible, Gebler says.

It's also important to note that a stem cell transplant will not benefit people with HIV who do not have cancer, as it is a very risky procedure that can lead to life-threatening infections, Gebler says. Most people are better off taking ART – often in the form of daily pills – which is a much safer and more convenient treatment option. stop the spread of HIVallowing people to enjoy long and healthy lives, he says. Moreover, a recently introduced drug called lenacapavir provides almost complete protection against HIV with just two injections per year.

However, efforts are being made to cure HIV with genetically editing immune cellsAnd prevent it with vaccines.