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City of Hope

20/10/2022

 
I grew up in the 1980s. I know I’m getting old, not far off 50 now, but I still remember the impact of the discovery of Human Immunodeficiency Virus (HIV) and the effect it had on society.
 
I remember the prejudice. I remember the offensive term Gay Related Immune Deficiency (GRID) and the unhelpful public health campaigns. I also remember the movie Philadelphia with Tom Hanks and Denzel Washington which showed how many people felt about HIV. I remember being in a class at school called “Personal and Social Vocational Education” where we were discussing what we would do if we came across a person with HIV bleeding to death… and I remember being shocked and surprised that I was the only person in the room who would try to help the person… 
Philadelphia - the movie that changed perceptions
Also, when I went to medical school in 1992 there was only one treatment for HIV, Azidothymidine (AZT). Over my career the treatments for HIV have increased dramatically and now there are many drugs for treating HIV infection BUT they all have one thing in common… THEY DO NOT CURE SOMEONE OF HIV.
 
Since the HIV pandemic began more than 70 million people have been infected with HIV and 35 million have died, and yet we still cannot cure anyone.
 
Why can you not cure someone of HIV?
There is a very good reason why someone cannot be cured of HIV. It has to do with the way the virus infects human cells.
 
HIV is a retrovirus. The name refers to the way that the virus enters into CD4 lymphocytes where it converts its RNA to DNA using its own enzyme called reverse transcriptase and inserts it into the cell’s DNA inside the cell’s nucleus. The DNA is then irreversibly implanted into the host cell. Every time the cell divides it carries the new DNA with it. Slowly the virus kills the cells and the CD4 count drops to almost nothing and the patient becomes at risk of opportunistic infections.
 
The drugs used to treat HIV essentially halt the infection and stop it getting worse. They can stop the virus spreading between cells and help the CD4 count recover to effective levels again. But they can’t remove the viral DNA from infected cells, and without the drugs the virus would just start spreading again. So, once you have HIV you always have HIV.
 
Well, that is until recently…
 
Can you actually cure HIV?
Now that is an excellent question. Theoretically it would be possible to cure HIV if you could remove all of the virally infected cells and replace them with uninfected cells. OK, this may sound like science fiction, but it actually isn’t.
 
We use a process for replacing white blood cells in routine medicine; it’s called a bone marrow transplant (BMT).
 
Now I say its “routine medicine” but that may be a bit of an exaggeration. We use BMTs to treat haematological cancers such as leukaemia when chemotherapy hasn’t worked. The basic principle is to kill off the patient’s original cancerous bone marrow using horrendously toxic chemotherapy and then give them someone else’s normal bone marrow instead. You have to wipe out all of the original bone marrow or the two different sets of white blood cells will start to attack each other, and the patient may well die. Also, there is the chance that the new bone marrow may not engraft, and the patient will be left with no immune system at all, and then they’ll die from that instead. So BMT is a bit of a risky procedure, and only undertaken when there is no better choice. It’s not that routine!
 
But you can see how this might treat HIV. The CD4 lymphocytes infected with HIV would be killed off by the chemotherapy and then uninfected cells could be put into the patient instead. However, the problem would be that there would still be some virus around outside of the cells and this will just infect the new CD4 cells, and the disease will reoccur… damn, and it was looking so good there for a moment…!
 
Hold on! What if you could find bone marrow resistant to HIV? Could you then donate bone marrow, and the new bone marrow wouldn’t get infected and the person would be cured of HIV? That sounds even more fantastical!
 
Well, it turns out you can…!
 
The “City of Hope” patient
A 66-year-old man from California, known as the “City of Hope” patient after the place where he was treated, has been cured of HIV.
 
This patient acquired his HIV in 1988 and has been living with the infection for many years, taking medication every day to keep it in check. When he was 63 years old he developed leukaemia for which it was eventually decided he needed a bone marrow transplant. A donor was found and by coincidence the donor is immune to HIV!
 
Yep, some people are immune to HIV. HIV enters lymphocytes through a protein called CCR5 (C-C chemokine receptor 5) on the cell wall. Some people have a mutation in the gene encoding CCR5 which makes the receptor resistant to HIV1 (you can still get HIV2 infection though!) added to this you have to have 2 copies of the resistant gene to have the resistance to infection. It is estimated that about 1% of European Caucasians have two mutated genes conferring resistance to HIV1. It is very rare!
 
So, in the case of the City of Hope patient, he was “coincidently matched” to a bone marrow donor who had two mutations in the CCR5 gene and was essentially given a bone marrow transplant resistant to infection with his HIV. His infected cells were killed, and he was given new ones that couldn’t get infected.
 
And it worked! Nearly a year and half later, not taking any HIV drugs, the “City of Hope” patient has no detectable HIV virus. He has been cured. He no longer has HIV.
 
And it turns out he isn’t the only person where this has happened.
 
Over the years 3 other people have been cured of HIV in this way. The first person is known as “The Berlin Patient” after where he was treated in 1998, but after him came an American called Timothy Ray Brown in 2008 and then a person in Britain called Adam Castillejo. Both of the later patients eventually waived their anonymity and hence why we know their names and their remarkable stories.
 
BUT before everyone starts to think this is this answer to HIV infection, just remember that bone marrow transplant is a risky procedure with significant risks to health and safety. And we have very good drugs now for controlling HIV such that if someone is diagnosed with HIV today, they will die from something else like old age. HIV is not the death sentence it appeared to be back in the 1980s when I was growing up.
 
It’s a great story though, and an amazing outcome for the “City of Hope” patient. It may also pave the way for future treatments of this virus.
 
In the meantime, if you are looking for a film to watch then I heartily recommend Philadelphia. It is not easy watching, you will need a box of tissues, but if you want to know what some of the public attitude to HIV was like when it was first discovered then this film will show you… and Tom Hanks won his first Oscar in 1993 for his role in this film… although he admits if the film was made today, it wouldn't be a straight white guy playing the role... True! it shows how influential this film was at changing societies perceptions. I think it should be a “must watch” for every healthcare professional.

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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