The 21st International AIDS conference takes place this week
A new study is replicating the treatment used to cure one man of HIV in 2008
One set of patients have seen their levels of HIV fall
In 2008, one man, Timothy Ray Brown, was cured of HIV.
Also known as the “Berlin patient,” Brown was considered cured of his infection after receiving two bone-marrow transplants to treat a separate disease he had been diagnosed with a few years earlier: acute myeloid leukemia.
The bone marrow he received came from a donor whose genes carried a rare mutation that made them resistant to HIV, known as CCR5-delta 32, which was transferred on to Brown.
Traces of the virus were seen in his blood a few years later, but remained undetectable despite him not being on antiretroviral treatment, meaning he was still clinically cured of his infection, according to his clinicians.
Despite various attempts on patients after him by scientists using this same approach, including a similar transplant in two Boston patients, Brown remains the only person known about who has been cured of HIV.
But a new study presented Sunday at the 2016 Towards an HIV Cure Symposium – ahead of the 21st International AIDS conference in Durban, South Africa, this week – revealed data on a new set of HIV positive patients whose reservoirs of HIV have fallen to very low levels after receiving a range of stem cell transplants similar to Brown’s.
The study is part of the EPISTEM project, a European project to investigate the potential for an HIV cure using stem cell transplantation, and provides further insight into the science underlying Brown’s success.
Everyone included in the project is in need of stem cell transplantation to cure severe blood disorders, in addition to being infected with HIV.
Can stem cells bear a cure?
The 15 patients monitored in the study to date are still on antiretroviral treatment, unlike Brown, but have received stem cell transplants. Three of them had their operations three years ago and have been studied in detail since.
“In two of the three patients we were unable to detect infectious virus in the blood of the patients,” said Annemarie Wensing, a virologist at the University Medical Center Utrecht who led the study. Tissue samples were also studied and one patient also had just traces of the virus hiding there.
“All HIV-infected patients that received a stem cell transplantation had a significant reduction of the viral reservoir in their body. This has not been demonstrated with other cure strategies,” Wensing said.
The minute levels of the virus that have been seen to date were not considered competent enough to replicate, according to the team.
“[This] will help us shape future HIV eradication strategies that could be applied at a larger scale than stem cell transplantation,” said Wensing.
But there’s a long road ahead.
“What’s interesting is that these patients have survived more than a year,” said Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity and co-chairwoman of the symposium. “There was concern that maybe when you take a CCR5-delta32 bone marrow it doesn’t engraft as well, but these patients have survived to 12 months.”
The next step will have to explore how they fare without treatment, Lewin added.
How the transplant works
The process of transferring resistance to HIV is extremely complicated – and rare.
Firstly, only 1% of Caucasians are estimated to carry the CCR5-delta 32 mutation that confers resistance to HIV, with other races having even fewer numbers. The genetic change means people lack a protein needed by HIV to enter blood cells.
The team also cannot be 100% sure whether the mutation is the only cause of the resistance to HIV or whether the many other stages of the transplant process play a role.
These include the body being totally cleared of its immune system using chemotherapy and irradiation ahead of it being rebuilt by the donor stem cells, and the potential for the newly formed immune cells to attack any remaining old ones that may be harboring HIV. Patients can also have one or two transplants.
“All those factors may be really important and we’re trying to tease it out,” said Monique Nijhuis, also from the Utrecht Medical Center who works on the project.
The unique and rare nature of the blood disorders affecting the patients also means they receive different treatments rather than everyone receiving the same treatment for comparison.
“Each person is like a micro-clinical trial in himself or herself,” said Asier Saez-Cirion from the Institut Pasteur, also involved in the project.