You all know me.
There are two things I really love:
- Studying HIV
- Using viruses for gene therapy
One would think I would be over-the-moon about the FDA approving human trials for a gene therapy to stop HIV. HIV! Gene therapy! YAY!!
When this line of research initially emerged, I WAS super excited:
Go read that.
Now, just to be clear, that was in no way a ‘functional cure’. No one in that small trial was ‘functionally cured’. But I still thought it was a great, creative step in a positive direction:
4– No way this is a viable world-wide ‘cure for HIV/AIDS’. But it is more viable than bone marrow transplants, and optimizing this protocol could get it cheaper/faster/safer for the developing world, aka, the place we really need a cure for HIV/AIDS.
But this is really cool. Really cool step in a positive direction.
… But then this happened:
An attempt to replicate the results seen in the really functionally cured ‘Berlin Patient’ did not result in a second person cured of HIV.
It resulted in yet another HIV death.
How? If HIV needs CCR5, and they replaced this patients bone marrow with cells that could not make CCR5, how did he die from AIDS?
Because while HIV likes CCR5 as a co-receptor to infect cells… it doesnt need it. The natural diversity of a patients quasispecies will contain some variants of HIV that can use a different co-receptor, CXCR4.
Viruses that use CXCR4 are assholes.
In this second patient, the radiation/chemo did not kill all of the cells latently infected with CXCR4-tropic viruses. When those viruses ‘woke up’ in their new environment, and no CCR5-tropic viruses as competition, they went nuts. Oh, and they must have also been resistant to antiretrovirals. For more complications.
So, yeah, the attempt to generate another Berlin Patient, another person ‘functionally cured of HIV!’… lead to a mans death.
“Oh my god, what are all those scientists going to do!” I thought. I knew there were a lot of people working on alternative ways of making people delta-CCR5, but if that can kill someone, there was no way they were going to be able to move forward with any clinical trials in people.
Best of luck to them. But we know what happens with patients treated with maraviroc (a protein that masks CCR5, doesnt delete it)– The quasispecies figures out a way around it. We know what happens if there is a CXCR4-tropic virus hiding out somewhere when we give someone a delta-CCR5 bone marrow transplant.
Rather than attempting a ‘functional cure’, I think it would make a lot more sense to use gene-editing technologies as an ‘HIV vaccine’— CCR5 viruses are the ones who ‘get through’ to establish infection via heterosexual and homosexual contact. CXCR4 viruses dont like doing that. *shrug*
So while an at-risk person might not be born delta-CCR5, does making them kinda-delta-CCR5 (these gene therapy approaches are not perfect) during exposures help them keep from getting infected in the first place? That would be fantastic!
And since you are not fighting with active viral replication and an already-established quasispecies with already established reservoirs, like you would be in an already-infected individual, Id think the risk of ending up with another CXCR4-dead-patient would be virtually non-existant.
But I dont work for this company and no one is asking me. So again, I wish them the best of luck. And I hope no one gets hurt.