It´s official. Taking antiretroviral drugs when you don´t have HIV cuts the risk that you´ll get infected. It´s exciting news, if not unexpected. But it´s going to be a major headache for politicians.
The results of the iPrEx trial, were published today in the New England Journal of Medicine (with pdf but not the supplementary bits here). The trial was among 2470 gay men and 29 transgendered women in six countries. Everyone took a pill a day; half were randomly assigned to take a combination of tenofovir and emtricitabine (sold by a now very happy Gilead under the brand name Truvada), the other half got a placebo. Neither participants nor researchers knew which was which.
The published headline: people who took Truvada were 44% less likely to contract HIV than people who took the dummy pill — an encouraging result, if not stunning. The real headline: people who actually took Truvada nearly all the time were 73% less likely to get HIV: a huge victory. It´s a smaller protective effect than using a condom all the time, of course. The thing is, we know that people aren´t good at using condoms all the time. And what these study results show us is that people aren´t very good at taking a pill every day, either, though they are keen to tell researchers that they do. One of the most striking things about the results was the mismatch between self-reported pill taking and measured levels of active drugs in people´s bodies.
The researchers cleverly did a study within a study to try and figure out how important it was that people dilligently took their pills. Among people who actually got Truvada, they compared intracellular and plasma drug levels in those who got HIV with a random sample of those on Truvada who didn´t get infected. They found that only 9% of those who got infected had measurable levels of the active drugs in their bodies, compared with 51% of those who didn´t get infected. To put it very bluntly, pre-exposure prophylaxis dosn´t work it you don´t take your pills.
Let´s remember that this was a group of men who were poked, prodded, bled and counselled by study staff every FOUR WEEKS, and they still weren´t taking their pills every day. It´s not all that clear why, though men who got the real drug were more likely than those on the fake pills to report nausea. It´s possible that people were less motivated to take their pills if they weren´t sure that they were actually getting real drugs, or even that if they were, the drugs would actually work as prevention. That may also be why guys in the study didn´t report any rise in risk behaviour (though it´s hard to imagine that they could; 80% of them reported at the start of the study that they´d had unprotected anal sex with someone who might be HIV infected). But it´s a worry; if PrEP goes mainstream for gay men, we´ll need a lot more work on how to get people to take their drugs more diligently.
Another major worry: 10 people who tested negative at the start of the study were actually in the very early stages of HIV infection. Both of the 2 who happened to be assigned to the Truvada group developed resistant forms of the virus, suggesting that giving these drugs in the early stages of infection when the virus is replicating very rapidly may fertilise resistant strains. More shocking to me (though less worrying) was that half of the men who had acute early HIV infection at the start of the study had symptoms of the infection, but none were picked up by the study physicians. This is a pet peeve of mine; bad enough in routine health services but nothing short of a disgrace in a study designed specifically to look at HIV infection in high risk men.
Worries about resistance aside, the news seems pretty good. So why do I say it´s a political nightmare? Because antiretroviral drugs are expensive; a lot of people who need them to prolong their lives can´t get them. Now we´re talking about giving them to gay guys so that they can go out and screw around as much as they like without having to think about using the cheaper and potentially more effective (but generally more bothersome) option of condoms. I´ve been a bit sniffy about this myself in the past, though I did spend about 15 years taking a pill every day so that I could have as much sex as I liked without contracting that long-term, life-changing sexually transmitted condition called pregnancy. But in many countries it is still very hard to give out condoms because it is seen to promote promiscuity. If we could figure out a way to improve adherance, putting ARVs on the public tab will probably save money overall. It´s certainly something we should be trying out in all sorts of different ways. That includes the possibility of “disco dosing” — taking pills only on the days when one has a pretty good idea that one´s going to end up barebacking. But as condoms have taught us, the fact that things work technically doesn´t necessarily mean they work in real life, let alone in politics. Even if we can find a better way to deliver pre exposure prophylaxis (implants? it´s what I do instead of pills these days against that other STD, and I love it) I think it is going to be a hard sell in many countries.
For more, see Roger Tatoud´s reflections on the wisdom of taking a pill every day to avoid taking a pill every day.
Still, for now the news is good. Click on the image at the top of this post, add your own positive Truvada story, and get 5 free mp3 downloads. I think it´s worth celebrating a bit while we can.