Gene therapy for HIV/AIDS prevention

Once you are infected with HIV-1, you are screwed.

Yes, we have antiretroviral therapies, but you will never be cured. You will never be free from the virus. And there is always a chance that the virus you are infected with will become resistant to the antiretroviral drugs used (this isnt just a distant chance, it does happen, regularly).

So the best way to 'stop' HIV/AIDS is to stop that initial infection from ever occurring.

We have condoms, and those work pretty damn well, but that is assuming people actually use them, and use them properly.

We have also tried giving high-risk people antiretrovirals before they are actually infected, but that hasnt worked out well either.

What we really need is an anti-HIV-1 vaccine. Well, we have those. So I guess a more accurate phrase is 'What we really need is an anti-HIV-1 vaccine that induces protective immunity'.

We know what a potential protective immune response looks like-- We have all these goddamn 'broadly neutralizing antibodies' sitting in our lab refrigerators. But due to the random nature of our immune responses, we cannot force anyone to create the protective immune response via vaccination.

But that does not mean we cannot force anyone to create the protective immune response.

We can take B-cells (the cells that produce antibodies) out of your bloodstream, infect them with a domesticated retrovirus or Adeno-Associated Virus which will deliver DNA to make the 'right' anti-HIV-1 antibody, and put those cells back into you. TAH-DAH! You now make broadly neutralizing antibodies against HIV-1 that might protect you if you were ever exposed.

Im not speaking in pure hypotheticals, here. We are absolutely moving towards that kind of treatment for the prevention of HIV-1 infection:

2008--
Building an HIV-Proof Immune System

2011--
Gene therapy can protect against HIV
Antibody-based protection against HIV infection by vectored immunoprophylaxis

David Baltimores group kinda protected CD4+ T-cells from HIV-1 infection in mice who got gene therapy, forcing them to produce one of these broadly neutralizing antibodies.

Very cool step forward, but of course there are lots of caveats, here.

Mice cannot be infected with HIV-1. So the mice used in this experiment were modified to have human-like CD4+ T-cells, which can be infected by HIV-1. But this is a very 'odd' animal model, here, in addition to the genetic modification to produce a human antibody.

We do not want humans to get infected with HIV-1 after this treatment, and momentarily protect their CD4+ T-cells for a while while the infection is just simmering, because then the virus would just evolve resistance to the GM antibody. While its neat to see some of the mice maintained their human CD4+ T-cells post infection, what we need to know if those antibodies can be in the right place at the right time in the right concentration to prevent infection from ever occurring (and how long after the initial treatment someone is protected). Maybe we could allow for a teeny-tiny local infection, if it is rapidly extinguished.

But with HIV-1, a tiny simmering spark can turn into a forest fire. These antibodies have to put that spark out, or we are just asking for GM-B-cell resistant HIV-1. Think it cant happen? These super awesome antibodies were isolated from humans. Many of whom died from AIDS related complications, populated by viruses resistant to their super awesome antibodies. Escape is what HIV-1 does.

Which also means we need to give this therapy to people who are at risk of contracting HIV-1. If we give it to people who already have HIV, then again, we are just asking for GM B-cell resistant HIV-1 populations.

The people most at risk of contracting HIV-1 live in the developing world. The people/places that cannot afford a treatment like this. For Petes sake many of them dont even have clean drinking water, and here we are in our labs saying 'GM B-cells are the way to go! YAY US!' Which is why I hate gene therapy as a weapon for fighting HIV. Its a luxury people who dont really *need* it could have, while the people who *need* it cant have it. It is scientifically marvelous, but on a personal level, I find it nauseating. But I am fighting that emotion. Sure, if this works, only rich people will get it. But over time, using it on rich people will allow for the development of newer, cheaper methods and technologies, which will allow us to get this kind of treatment to the developing world.

We really dont have anything other than condoms, at this point. If this kind of gene therapy works in humans, it provides us with a starting point. From there we can make things better and cheaper. And it doesnt mean we are all going to suddenly stop trying to formulate a good anti-HIV-1 vaccine.

So good on David Baltimores group. I cant wait to see what this kind of treatment does in non-human primates.