After nearly 12 years of the first patient being cured since the global epidemic began a second patient appears to have been cured of H.I.V infection; findings confirm that a cure for this infection is possible, however difficult it may be.
Published in the journal Nature and presented at the Conference on Retroviruses and Opportunistic Infections, the case is described as being a long term remission, some are calling it a cure, but it is hard to know how to define this when there are only two known instances.
Both milestone cases are the result of bone marrow transplants that were given to the infected patients from donors with a mutation in the CCR5 protein, however, these transplants were underwent with the intention of treating both patient’s cancer not H.I.V.
In the near future bone marrow transplants are unlikely to be a realistic treatment option. Transplants are risky and can have side effects that can last for years, drugs are now available which can help to control H.I.V infection if the prescribed regimen is strictly adhered to.
Rearming the body with immune cells similarly modified to resist the H.I.V virus may also success as a practical more practical treatment than bone marrow transplantation.
“This will inspire people that cure is not a dream, it’s reachable.” says Dr. Annemarie Wensing of the University Medical Center Utrecht.
This 2nd patient from London wished to remain anonymous, but has said he never thought he would be cured of both his cancer and H.I.V infection at the same time during his lifetime.
Back in 2007 when a German doctor described the first cure in the Berlin patient, it was displayed on poster at the back of a conference room and gained little attention. But when it was clear he had been cured, around the world scientist set out to duplicate the results with other cancer patients that were also infected with H.I.V. Unfortunately the virus came back in case after case around 9-10 months after antiretroviral drugs were stopped, or the patients died of cancer, and the many failures left the scientific community wondering whether the first patient was a fluke.
The first patient had leukemia and after chemotherapy failed needed 2 bone marrow transplants which came from a donor with a mutation in the CCR5 protein which rests on the surface of certain of certain immune cells, the virus uses the protein to enter those cells but is not able to latch onto the mutated version. Additionally the first patient was given harsh immunosuppressive drugs that are no longer used, he suffered severe complications for months and was placed into an induced coma at one point and nearly died.
“He was really beaten up by the whole procedure, And so we’ve always wondered whether all that conditioning, a massive amount of destruction to his immune system, explained why Timothy was cured but no one else.” says Dr. Steven Deeks of the University of California.
The second patient had Hodgkin’s lymphoma, and like the first patient received a bone marrow transplant from a donor with the CCR5 mutation in 2006. He also received immunosuppressive drugs, but much less intense, and he stopped taking antiretroviral drugs in 2017 and became the second patient to remain H.I.V virus free for more than a year after stopping.
Although the London patient was not as ill as the Berlin patient after the transplant the procedure worked about as well with the transplant destroyed the cancer without harmful side effects, and the transplanted immune cells now resistant to the virus appear to have replaced his vulnerable cells.
Most people with the H.I.V resistant delta 32 mutation are of Northern European descent, and IciStem maintains a database consisting of around 22,000 of such donors. Scientists are currently tracking 38 H.I.V infected patients who have received bone marrow transplants, including 6 from donors without the mutation.
The London patient is #36 on this list, and #19 the Dusseldorf patient has been off antiretroviral drugs for several months. The London patient’s blood has been repeatedly analyzed for signs of the virus and a weak indication of continued infection was seen in 1 of 24 tests, but was said to be the result of sample contamination as the most sensitive tests didn’t find any circulating virus; antibodies to H.I.V were still present but levels declined in a similar trajectory to the first patient.
“I’m not sure what this tells us. It was done with Timothy Ray Brown, and now here’s another case — ok, so now what? Now where do we go with it?” says Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases.
One possibility may be to use these findings to develop gene therapy approaches to knock out CCR5 on immune cells or their predecessor stem cells, once resistant to the virus these modified cells should eventually clear the body of infection from the H.I.V virus; several companies are pursuing this but have not been successful.
“There are a number of levels of precision that must be reached.There are also concerns that you might do something untoward, and if so you might wish to have a kill switch.These are dreams, right? Things on the drawing table.These dreams are motivated by cases like this — it helps us to imagine what might be done in the future.” says Dr, Mike McCune.
“This is only going to work if someone has a virus that really only uses CCR5 for entry — and that’s actually probably about 50 percent of the people who are living with H.I.V., if not less,” says Dr. Timothy J. Henrich of the University of California.
Any such approach would still leave the patient vulnerable to a form of H.I.V called X4 which employs a different protein called CXCR4 to enter the cells that may multiply in absence of competition. There is one report of a patient who received a transplant from a delta 32 donor, but later rebounded with the X4 virus. The second patient is taking a daily pill against X4 to prevent infection as a precaution.
