A second person may have been cured of HIV, ten years after the first patient, Timothy Ray Brown, known as the “Berlin patient”, received a similar stem cell transplant and is still free of the virus. The results are described in a paper published on 5 March in Nature (1).
While HIV infections can typically be kept under control by a cocktail of anti-retroviral drugs, they are impossible to cure. But the fact that Brown was not a one-off, suggests a cure may be possible.
Blood cancer treatment involves killing off the cells in the bone marrow with radiotherapy or chemotherapy and then transfusing stem cells from a healthy donor. Both men received stem cell transplants to treat leukaemia, but the cells had a mutation in the gene for CCR5, a cell surface molecule that many HIV strains use to infect cells.
In the first case, Brown received an aggressive cancer treatment of radiotherapy followed by chemotherapy and finally, a blood-stem-cell transplant for his cancer. At the same time, Brown was receiving an experimental treatment for HIV.
The “London patient”, who remains anonymous, did not undergo radiotherapy but similar to Brown, received chemotherapy and a drug that targets cancer cells prior to the transplant. In this case, Dr Ravindra Gupta and his team from the University of Cambridge selected a stem cell donor with two copies of a mutation in the CCR5 gene, which gives people resistance to HIV infection.
The mutation prevents the HIV virus from attaching to CCR5 receptors on the surface of white blood cells, thereby preventing the virus from attacking the immune system. After the transplant, the virus seemed to have vanished and 18 months later, the patient is no longer taking anti-retroviral drugs and the infection has still not re-emerged.
Doctors have resisted using the word “cure” and have instead opted for “long-term remission” since they have not yet examined other tissues in the body and the timeframe is still too short to make any solid conclusions.
The “London patient” is the one of more than 30 HIV-infected people with blood cancers who have received or will soon receive stem cell transplants as part of study set up by the amfAR, the Foundation for AIDS Research, an international nonprofit organization dedicated to AIDS research.
A handful of transplants in other HIV-infected patients were not successful. In these cases, the virus was controlled for a brief period without anti-retroviral drugs but then the infection either rebounded or the patient died from their leukaemia or lymphoma.
The treatment is not appropriate for most people with HIV. For those who don’t have cancer, the risks of a bone marrow transplant ― a procedure that can have fatal complications ― far outweigh the potential benefits. Whereas, finding a donor with the CCR5 mutation for HIV patients with cancer who are in need of a transplant would not add any additional risk.
Nonetheless, the findings suggest a cure may be possible and offer hope for potential gene therapies targeting the CCR5 gene that could perhaps reach a larger cohort of HIV patients.
(1) Gupta R.K. et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature (2019). DOI: 10.1038/s41586-019-1027-4