A 53-year-old man in Germany, referred to as the "Düsseldorf patient," has become at least the third person to be declared cured of HIV. The man underwent a bone marrow transplant in 2013, replacing his bone marrow cells with HIV-resistant stem cells from a donor who carried the genetic mutation CCR5Δ32/Δ32, which prevents the CCR5 protein from being expressed on the cell surface. HIV uses this protein to enter immune cells, making the cells resistant to the virus.
The technique was first used on Timothy Ray Brown, the "Berlin patient," who was cured of HIV after a bone marrow transplant in 2007. The same procedure was used to cure the "London patient," Adam Castillejo, in 2019, and a New York patient who has been HIV-free for 14 months.
The Düsseldorf patient had extremely low levels of HIV, thanks to antiretroviral therapy (ART), when he was diagnosed with acute myeloid leukaemia. In 2013, a team led by virologist Björn-Erik Jensen at Düsseldorf University Hospital in Germany destroyed the patient's cancerous bone marrow cells and replaced them with stem cells from a donor with the CCR5Δ32/Δ32 mutation.
Over the next five years, Jensen's team took tissue and blood samples from the patient. They found immune cells that specifically reacted to HIV, which suggested that a reservoir of HIV remained in the man's body. They also found HIV DNA and RNA in the patient's body, but these never seemed to replicate. In an effort to understand more about how the transplant worked, the team ran further tests, which included transplanting the patient's immune cells into mice engineered to have human-like immune systems. The virus failed to replicate in the mice, suggesting that it was nonfunctional. The final test was for the patient to stop taking ART, which he did in 2018, and he has remained HIV-free since.
While bone-marrow replacement is unlikely to be rolled out to people who don't have leukaemia because of the high risk associated with the procedure, several teams are testing the potential to use stem cells taken from a person's own body and then genetically modified to have the CCR5Δ32/Δ32 mutation, which would eliminate the need for donor cells.
Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led the team that treated Castillejo, says the latest study "cements the fact that CCR5 is the most tractable target for achieving a cure right now." Timothy Henrich, an infectious-disease researcher at the University of California, San Francisco, says the study is very thorough. That several patients have been successfully treated with a combination of ART and HIV-resistant donor cells makes the chances of achieving an HIV cure in these individuals very high.