Seventh Patient Cured of HIV: Why Scientists are Excited
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. Although he has been virus-free for almost six years, he is only the second person to receive stem cells that are not naturally resistant to the virus.
Expert Reactions and Historical Context
“I’m quite surprised that it worked,” says Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led the team that treated one of the other patients now free of HIV.
Timothy Ray Brown, the Berlin patient, was the first to be found HIV-free after a bone marrow transplant. He and a few others received donor stem cells with a mutation in the CCR5 gene, which many scientists believed was key to curing HIV.
New Findings Challenge Previous Assumptions
However, the latest case — presented at the 25th International AIDS Conference in Munich, Germany, this week — challenges that view. The patient, referred to as the next Berlin patient, received stem cells from a donor who had only one copy of the mutated gene, meaning their cells still express CCR5, but at lower levels than usual.
This case shows that curing HIV “is not just about CCR5,” says Sharon Lewin, infectious disease physician and head of The Peter Doherty Institute in Melbourne.
Implications for Stem-Cell Transplantation
The findings broaden the donor pool for stem-cell transplants, a risky procedure mostly used for leukemia patients. About 1% of Europeans have mutations in both CCR5 gene copies, while 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. Approximately 40 million people globally live with HIV.
Case Study: Six Years HIV-Free
The next Berlin patient was diagnosed with HIV in 2009 and developed acute myeloid leukemia in 2015. His doctors could not 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, similar to the patient. The stem-cell transplant was performed in 2015.
The cancer treatment went very well, says Christian Gaebler, a physician-scientist and immunologist at Charité — Berlin University Medicine, who presented the research. Within a month, the patient’s bone marrow stem cells had been replaced with the donor’s. The patient stopped taking antiretroviral drugs in 2018, and now, almost six years later, researchers cannot find evidence of HIV replication in the patient.
Exploring Success Factors and Future Directions
Previous stem cell transplants from donors with normal CCR5 genes saw the virus return weeks or months after stopping antiretroviral therapy, except in one case. In 2023, Asier Sáez-Cirión from the Pasteur Institute reported on the Geneva patient, who had been off therapy for 18 months. Sáez-Cirión says the person remains free of the virus, about 32 months later.
Researchers are now investigating why these two transplants succeeded where others failed.
They propose several mechanisms. First, antiretroviral treatment significantly reduces the amount of virus in the body. Additionally, chemotherapy before the stem-cell transplant kills many of the host’s immune cells, where residual HIV might be hiding.
The transplanted donor cells may then mark remaining host cells as foreign and destroy them, along with any virus present in them. The rapid replacement of the host’s bone marrow stem cells with those from 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 CCR5 gene copy with a mutation may have created an extra barrier to the virus entering cells, says Gaebler.
Implications for Gene-Editing Therapies
The case also impacts early-stage clinical trials where therapies edit the CCR5 receptor from a person’s cells using gene-editing techniques like CRISPR–Cas9, according to Lewin. Even if these therapies do not reach every single cell, they could still have a significant impact.
Read the original article on: Nature
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