Second 'Berlin Patient' Appears to be Cured of HIV Following Stem Cell Transplant

There is now a successor to the person referred to in medical literature as the “Berlin patient,” who made history in 2008 as the first person cured of HIV after a stem cell transplant. A 60-year-old man appears to be cured of HIV more than five years after receiving a stem cell transplant to treat acute myeloid leukemia (AML), a team of German investigators reported this week. However, unlike other patients cured of HIV, the second “Berlin patient” did not receive stem cells from an HIV-resistant donor.

In previous cases, patients who were cured of HIV infection following stem cell transplants received stem cells from donors that exhibited a rare mutation in the CCR5 gene (CCR5Delta32 mutation), which is present in around one percent of the European population. The CCR5 receptor is a protein on the surface of immune cells that HIV uses to enter and infect the cells. The Delta-32 mutation in the CCR5 gene results in a defective receptor, preventing HIV from gaining entry. This mutation results in the absence of a docking site for HIV in immune cells, which protects against infection.

In this most recent case, however, there was no suitable HIV-immune person for the stem cell donation. Instead, investigators found a donor who carried the mutated version of the docking site on her cells in addition to the normal version of the CCR5 receptor.

"This is the case when a person inherits the Delta-32 mutation from only one parent,” said Olaf Penack, MD, senior physician at the treating clinic, Charité - Universitätsmedizin Berlin. “However, the presence of both receptor versions does not confer immunity against HIV."

Despite the donor’s lack of immunity to HIV, the patient has remained free of evidence of HIV infection for more than five years after stopping the recommended antiviral therapy on his own accord. According to investigators, it is still unclear why the stem cell transplant led to a cure in this case while the virus multiplied again in comparable cases. The researchers are considering several potential factors.

"This means that the cure is probably not due to the genetic CCR5 equipment of the stem cell donor but rather to the fact that the transplanted immune cells of the donor eliminated all of the patient's HIV-infected cells," said Christian Gaebler, MD, MSc, an HIV expert and working group leader at the Clinic for Infectious Diseases and Intensive Care Medicine at the Charité and the Berlin Institute of Health. "By replacing the immune system, we have apparently destroyed all of the virus's hiding places, so that the HIV virus could no longer infect the donated, new immune cells."

The researchers hope that understanding the factors that led to the second Berlin patient’s cure could pave the way for new therapies, potentially making HIV cures more accessible and widespread.

“Due to the considerable risks associated with stem cell transplantation, this procedure is not suitable for use in all HIV infections,” Gaebler said. “As soon as we have a better understanding of which factors contributed to the removal of all HIV hiding places in the second Berlin patient, the findings can hopefully be used to develop new treatment concepts such as cell-based immunotherapies or therapeutic vaccines."