Timothy Ray Brown, also known as the “Berlin patient,” is the only human believed to have been cured of HIV, following a bone marrow transplant from a donor immune to the virus. Now, researchers of a new study published in PLOS Pathogens have tested the potential mechanisms underlying this cure in monkeys.

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Researchers found that although radiation exposure prior to stem cell transplantation reduced the viral reservoir in monkeys infected with a chimeric simian/human immunodeficiency virus, it failed to cure them.

In 1995, Brown was diagnosed with HIV (human immunodeficiency virus). After undergoing antiretroviral therapy (ART) for the infection for more than 10 years, he was also diagnosed with acute myeloid leukemia.

Brown was treated with radiation and chemotherapy, before receiving a bone marrow transplant from a donor who possessed a mutation that wipes out the function of CCR5 – a gene that allows HIV to enter human cells.

Last year, a study confirmed that Brown had been functionally cured of HIV. He had no detectable HIV replication in his blood and had gone without ART for 5 years.

According to the researchers, led by Guido Silvestri of Emory University in Atlanta, GA, there are many possible mechanisms that could have contributed to Brown’s cure. They note that the CCR5 mutation in donor cells may have protected the patient against HIV infection, or the donor cells may have deemed the host cells as invaders and attacked them – a “graft versus host” response – eliminating any cells infected with HIV that survived radiation.

Furthermore, the removal of blood and immune cells after radiation exposure could have destroyed all or the majority of infected cells that had previously avoided the clutches of ART. For the first time, Silvestri and colleagues tested this strategy in monkeys.

The team used six rhesus macaque monkey models infected with a chimeric simian/human immunodeficiency virus (SHIV). Simian immunodeficiency virus (SIV) is closely related to HIV and infects primates.

Prior to infection, hematopoietic stem cells were harvested from three of the monkeys. After infection, all of the monkeys received ART.

The monkeys that had their hematopoietic stem cells harvested were then exposed to high-dose radiation. The radiation killed the majority of existing blood and immune cells. Around 94-99% of CD4-T cells in the blood were destroyed, which the researchers say is the primary target of HIV infection.

These three monkeys were then transplanted with their own virus-free hematopoietic stem cells, and within 3-6 weeks, the stem cells regenerated blood and immune cells. ART was then stopped for all six monkeys.

The researchers were not surprised to find that HIV quickly reappeared in the three monkeys that did not receive transplants.

However, the team also found that HIV came back in two of the monkeys that did receive transplants. The third transplanted monkey had to be euthanized 2 weeks after ART ceased, due to kidney failure. Although it did not have detectable levels of HIV in its blood at time of death, the researchers identified viral DNA at low levels in some of its tissues.

Although their findings suggest that radiation exposure prior to stem cell transplantation does not cure HIV, the team says the procedure still shows promise:

This experiment demonstrated that autologous hematopoietic stem cell transplantation is a feasible intervention that can lead to a marked reduction of the virus reservoir in the peripheral blood, and can be used as an experimental in vivo platform to test innovative interventions aimed at curing HIV infection in humans.”

They note that although this process likely reduced viral reservoir in Timothy Ray Brown, his cure was more likely down to the stem cell transplantation from a donor with a CCR5 mutation or a “graft versus host” response.

Medical News Today recently reported on a commentary published in the journal Science, in which researchers say the HIV rebound in the “Mississippi baby” believed to have been cured of HIV may help to understand what needs to be done to eradicate the virus completely.