Sometimes I am the worlds worst advocate for my own research.
Yes, its fantastically cool.
Yes, we learn more about the world and how life evolves on it.
But THE REASON I do HIV-1 research is to help ultimately create an HIV-1 vaccine. The only way we are going to beat HIV-1 is to stop new infections, and to stop new infections, we need a vaccine…
Or, everyone could just wear condoms, which reduce HIV-1 transmission ~85%, and we could cut this bastard off at its head in a few generations and I can go do something else.
Well, the thing is, things arent that simple. Half the people infected with HIV-1 are women, and the vast majority of them are infected via heterosexual contact. Not every woman has a say in when/where/how she has sex. So not every woman can speak up and say “Yeah, you are so wearing a condom, dude, lol!” Same thing goes for some men.
Ideally, we would like to be able to help the people most at risk of acquiring HIV-1 infection. Put the power in their hands, not the hands attached to the guy not putting on a condom. One way we can do this I talked about a week ago— microbicides. A gel that could be used pre/post sex to help stop HIV-1 transmission.
Weve now got one that works. Kinda.
They gave a gel containing tenofovir to 445 women, placebo to 444. They were supposed to use it before and after sex, but no more than 2 doses in 24 hours. And they did. There was a very high compliance rate, and the women didnt mind the gel at all– over 97% were totally cool with it.
The gel reduced HIV-1 acquisition by 39% (even higher for women who were really strict about using it properly– 54%).
Thats no 80-90%, but hell, Ill take 40-50% over someone not being able to protect themselves at all.
Also awesome: Applying the drug in small quantities where its needed in a microbicide, instead of giving oral (systemic) antiretrovirals as a prophylactic means you get to avoid a lot of unwanted physical side effects. The ‘worst’ they got with this microbicide? Some people got diarrhea. No renal failure.
What I am actually interested in discussing about this, is the evolutionary aspect. If we put this drug in microbicides, arent we just going to get lots of drug resistant HIV-1 spreading?
By chance, there are HIV-1 variants in the transmitting sexual partner that are resistant to tenofovir. If that person is not actively on tenofovir, there is no reason to assume resistant variants would be at any higher frequency in the quasispecies than any other random variant of the consensus. Only a fraction of the quasispecies is represented in one particular ejaculation. And that minority variant must be at the right place at the right time to successfully mediate infection in the new host.
So thus far, weve already taken an unlikely event and made it more unlikely-er.
Now, this ‘drug resistant’ variant is in a new host. Once it gets to the lymph node and really gets its claws into this new host, the virus will start rebuilding a new quasispecies. A drug resistant quasispecies? NO. Tenofovir is not at pharmacological concentrations systemically in this new host– its only in the microbicide. When tenofovir is no longer a selective pressure, thus the virus just drifts. Random mutation, drift. It loses tenofovir resistance because it doesnt particularly need it. Worse still, HIV-1 drug resistance almost universally comes at a fitness cost to the virus. It doesnt particularly want the mutation there at all, unless of course, the drug is there, and only the variants with the appropriate mutation survive.
The point at which we all get screwed is when HIV-1 figures out how to be resistant to tenovir… AND maintain high fitness. Chance mutation 1 gives you the resistance and low-level replication. Chance mutation 2 lets it replicate a little faster. Chance mutation number 3 and 4 lets it go a little bit faster. The virus racks up compensatory mutations until ‘wild-type virus’ and ‘drug resistant virus’ are equally fit, whether the drug is there or not.
THAT is when we are screwed.
But that should just happen if the person has a lot of tenofovir around to act as a strong selective pressure. The amount in the microbicide was not enough to actively select for the mutant, because the researchers here couldnt find drug resistant HIV-1 in the people with the tenofovir gel that still got infected.
So right now? This is a fix Im wiling to gamble on, evolutionarily.
… or we could just wear goddamn condoms.