In a significant development, a 53-year-old man in Germany has reportedly become the third person with HIV to be declared cured. The patient, known as the ‘Düsseldorf patient,’ underwent a procedure in which a donor replaced his bone marrow cells with HIV-resistant stem cells.
This procedure appears to have eliminated the virus reservoirs in the man’s body, allowing him to remain HIV-free even after stopping antiretroviral therapy (ART) in 2018. While ART has effectively lowered the virus to undetectable levels, it cannot eliminate the virus reservoirs in the body.
According to a study published in Nature, this latest development is a significant step towards finding a true cure for HIV. This particular stem-cell technique was initially tested on Timothy Ray Brown, the Berlin patient. He got a bone marrow transplant after being diagnosed with acute myeloid leukemia in 2007. His own stem cells were replaced with those of a healthy donor.
Brown’s medical team chose a donor with the CCR532/32 mutation because it hinders the generation of the CCR5 cell-surface protein. Since HIV requires the protein to enter immune cells, removing it through mutation renders the cells immune to the virus. Brown has not had ART since the operation and will remain HIV-free until he died in 2020.
Further studies were done by the study team to further understand how the transplant works, such as transplanting the patient’s immune cells into mice bred to have human-like immune systems. Because the virus was not multiplying in the mice, it had to be dormant. As a last option, the patient was told to discontinue ART. This demonstrates that removing HIV from the body is “not impossible, but extremely difficult,” according to Jensen.
The transplant recipient said in a statement that his rehabilitation had been “arduous” and that he expected to spend most of his time fundraising for medical research. Timothy Henrich, an infectious disease expert and UCSF professor praised the study for its breadth. Given the effectiveness of ART and HIV-resistant donor cells in curing many patients, a cure for HIV in these people is very likely.
Gupta concurs but adds that once inside a person, the virus can adapt and discover new entry points. Additionally, it is unknown if the cancer medication the patients had before their bone marrow transplants affected the effective removal of HIV by slowing the growth of infected cells.
Yet, because of the significant risk of rejection, bone marrow replacement is unlikely to be administered to healthy patients. This is especially true for people who are not affected by leukemia. Numerous research teams are considering using genetically engineered stem cells with the CCR532/32 mutation (autologous or generated from the patient’s body).
As a result, we would no longer need to rely on cell donors. As per Jensen, many additional people with HIV and cancer have had stem cell transplants from donors with the CCR532/32 mutation; however, it is too early to tell if they are virus-free.
His team intends to investigate if a transplant recipient who had a higher reservoir of HIV at the time of the transplant may recover and clear their body of any leftover infections. “The idea that CCR5 is the most tractable target for delivering a therapy right now,” says Ravindra Gupta, a microbiologist at the University of Cambridge, UK, and head of the team that treated Castillejo, has been strengthened by research.