Seventh Patient ‘Cured’ of HIV: Why This Breakthrough Excites Scientists

A 60-year-old man in Germany has become at least the seventh person with HIV to be declared free of the virus after receiving a stem-cell transplant. This man, who has been virus-free for nearly six years, is only the second person to achieve this without receiving stem cells resistant to the virus.

“I am quite surprised that it worked,” says Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led a team that treated another person now free of HIV. “It’s a big deal.”

The first person to be declared HIV-free after a bone-marrow transplant for blood cancer was Timothy Ray Brown, known as the Berlin patient. Brown and a few others received special donor stem cells carrying a mutation in the CCR5 gene, which encodes a receptor used by most HIV strains to enter immune cells. These cases suggested that CCR5 was the best target for an HIV cure.

The latest case, presented at the 25th International AIDS Conference in Munich, Germany, challenges this notion. The patient, referred to as the next Berlin patient, received stem cells from a donor with only one copy of the mutated gene, meaning their cells still express CCR5 but at lower levels than usual.

This case sends a clear message that finding a cure for HIV is “not all about CCR5,” says Sharon Lewin, an infectious-disease physician who heads The Peter Doherty Institute for Infection and Immunity in Melbourne, Australia.

Ultimately, the findings expand the donor pool for stem-cell transplants, a risky procedure typically offered to people with leukemia but unlikely to be widely used for most individuals with HIV. While roughly 1% of people of European descent carry mutations in both copies of the CCR5 gene, about 10% have one mutated copy.

The case “broadens the horizon of what might be possible” for treating HIV, says Sara Weibel, a physician-scientist studying HIV at the University of California, San Diego. Around 40 million people are living with HIV globally.

Six Years HIV-Free

The next Berlin patient was diagnosed with HIV in 2009 and developed acute myeloid leukemia, a type of blood and bone-marrow cancer, in 2015. His doctors couldn’t find a matching stem-cell donor with mutations in both copies of the CCR5 gene, but they found a female donor with one mutated copy. The patient received the stem-cell transplant in 2015.

“The cancer treatment went very well,” says Christian Gaebler, a physician-scientist and immunologist at Charité — Berlin University Medicine, who presented the work. Within a month, the patient’s bone-marrow stem cells were replaced with the donor’s. The patient stopped taking antiretroviral drugs, which suppress HIV, in 2018. Almost six years later, researchers can’t find evidence of HIV replicating in the patient.

Shrunken Reservoir

Previous attempts to transplant stem cells from donors with regular CCR5 genes have seen the virus reappear weeks to months after patients stopped taking antiretroviral therapy, except in one case. In 2023, Asier Sáez-Cirión, an HIV researcher at the Pasteur Institute in Paris, presented data on the Geneva patient, who has been without antiretroviral therapy for 18 months and remains virus-free about 32 months later.

Researchers are trying to understand why these two transplants succeeded where others failed. They propose several mechanisms: antiretroviral treatment significantly reduces the virus in the body, and chemotherapy before the transplant kills many of the host’s immune cells where residual HIV lurks. Transplanted donor cells might then mark leftover host cells as foreign and destroy them, along with any virus they contain. The rapid and complete replacement of the host’s bone-marrow stem cells with those of the donor might also contribute to the swift eradication. “If you can shrink the reservoir enough, you can cure people,” says Lewin.

The fact that both the next Berlin patient and his stem cell donor had one mutated CCR5 gene copy might have created an extra barrier to the virus entering cells, says Gaebler.

This case also has implications for therapies in early-stage clinical trials where the CCR5 receptor is sliced out of a person’s cells using CRISPR–Cas9 and other gene-editing techniques, says Lewin. Even if these therapies don’t reach every single cell, they could still make a significant impact.