Once again, a seriously ill man has been freed from HIV thanks to a stem cell transplant – the seventh in the world. But this German man in his sixties received cells containing only one copy of the gene that protects against HIV, instead of two, like his predecessors. The way his immune system responded provides starting points for more broadly applicable treatments.
The results with the new patient are published on Monday in the scientific journal Nature.
The German was diagnosed with the human immunodeficiency virus (HIV) in 2009. In 2015 he was diagnosed with acute myeloid leukemia, a blood cancer. To cure that cancer, a stem cell transplant is needed. The doctors at the Charité University Clinic in Berlin looked for donors with a specific change in the gene that codes for the protein CCR5. This protein is HIV’s gateway to human white blood cells. Some people naturally have a mutation in the gene called CCR5delta32. Their cells are less easy to infect by HIV.
The handful of patients who were previously freed from HIV with a stem cell transplant received stem cells from donors with two copies of CCR5delta32. The idea was that this is crucial for healing.
No HIV to be measured
The now reported finding is actually a coincidence: no matching donor could be found with two copies, but one could be found with one copy of the required gene. The transplant was done in consultation with the patient. With success: three years after the transplant, the German stopped taking virus-inhibiting medications. Now, after six years, HIV is still not detectable in his blood.
The study shows that even with stem cells from people who carry only one copy of the CCR5 delta32 gene, HIV can be suppressed for years. That increases the number of potential donors: about 1 percent of people in Europe have two copies, approximately 9 percent of the European population has one.
It was striking that this patient also already had a copy of that protective gene. As a result, the amount of virus in his body was not that high.
The treatment is very risky. That is why it is only tried out on HIV patients who need a stem cell transplant due to life-threatening blood cancer. After a heavy course of chemotherapy, a patient receives stem cells from a suitable donor through an IV. These stem cells must settle in the patient’s bone marrow and produce healthy blood and immune cells there. HIV can no longer enter those cells to reproduce itself.
This new mindset could be a way to create a more inclusive medicine.
“This study is very interesting for several reasons,” responds virologist Anne Wensing of the UMC Utrecht. She coordinates a European research project with these patients. “The treatment worked quickly for this man, and his innate immune system responded strongly. This effectively eliminated cells containing HIV. Probably also because he did not have a large reservoir of the virus in his body.”
Wensing is now looking for ways to activate the cells of that innate immune system, so-called NK cells. “That protective genetic mutation only occurs in white people, not in black people. While black women are by far the largest group of people with HIV. This new way of thinking could be a way to create a more inclusive medicine.” She thinks such a drug could be used at an early stage, when the amount of virus is not yet that great.
Used for life
The American Timothy Brown was the first person to get rid of HIV after a stem cell transplant, also at the Charité university clinic in Berlin. He was known as ‘the Berlin patient’. In 2009, his doctors declared him HIV-free. But the leukemia returned and Brown died in 2020.
After Brown, five other patients followed from 2019. The man from this new study is the seventh, and is called ‘the second Berlin patient’.
Being global almost 41 million people infected with HIV, more than a million new people are added every year. HIV weakens the immune system and, without treatment, leads to the fatal disease AIDS. Patients can keep the virus under control with daily virus inhibitors. These drugs must be used for life and are not available everywhere. Scientists are therefore looking for a curative treatment.
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