D-day for the Pill for HIV

So what just happened is that on 16 October the researchers behind the PROUD trial, in which 545 gay men in England were given daily pills of the anti-HIV medicine Truvada(R) either immediately or after a year's delay, announced that what had been intended as a mere pilot study had been so dramatically successful that they were offering all participants immediate PrEP...

Two studies mark a turning point in HIV prevention

The media coverage of the unexpectedly early success of two trials of pre-exposure prophylaxis - PrEP - has generally been positive, sometimes overly so ("NHS to offer tablet which can reduce HIV risk by 90%" said The Independent - not yet it won't).

But I haven't seen anything that actually explains why the results of the PROUD and IPERGAY studies are so important, or why they represent a gear-change in the accelerating race towards the end of HIV.

To recap: PrEP means taking an anti-HIV pill daily, or in advance of exposure, to prevent HIV infection. It's not a new idea: think quinine in pink gin to stop malaria, think statins to stop heart attacks, think above all of the contraceptive pill.

It's different from post-exposure prophylaxis (PEP), which means taking, so to speak, the morning-after pill.

So what just happened is that on 16 October the researchers behind the PROUD trial, in which 545 gay men in England were given daily pills of the anti-HIV medicine Truvada(R) either immediately or after a year's delay, announced that what had been intended as a mere pilot study had been so dramatically successful that they were offering all participants immediate PrEP.

Less than two weeks later, the scientists behind the IPERGAY trial - which offered 400 French and Canadian gay men PrEP (or placebo pills) to be taken in advance of sex - announced that they, too, were offering PrEP to all the men on placebo because, prompted by PROUD, they'd taken a look at their data and found high levels of effectiveness too.

Both teams were cagey about putting figures on what they'd seen in their studies but IPERGAY's lead researcher Jean-Michel Molina let slip to a couple of gay magazines that effectiveness was in the order of 80%; PrEP stopped four out of five infections that would otherwise have happened. PROUD is unlikely to have lower effectiveness than this, and may well have higher.

There's all sorts of reasons these results are great news. Europe has lagged behind the US and even Africa in HIV prevention research - yet here were European researchers delivering pivotal results. IPERGAY tested a new way of taking PrEP - when you think you'll need it, rather than daily - which means people will now have choice of two effective ways of taking it. PROUD was designed to be as close to 'real life', to what it's probably going to be like getting PrEP on the NHS, as possible.

Thirdly, the researchers involved community members from the outset not just in consultation but in designing the trial and making decisions: one result is myself, who is co-chair of PROUD not because I'm any kind of scientist but because I'm an HIV activist.

But the central importance of both IPERGAY and PROUD is that these are true effectiveness results, not efficacy ones.

These two terms are often used interchangeably, even by scientists, but generally efficacy means the effect a treatment can have while effectiveness means the effect it actually does have.

Efficacy figures are often quoted because they look better: they measure the effect of the treatment on the people who actually took it the way they were supposed to. Effectiveness measures the effect of the treatment on everyone allocated to it - regardless of whether they took it or not. It's a much fairer measure, as it shows not just whether the treatment works, but whether people like it or want it.

In IPERGAY and PROUD, they did: as a result, Truvada cut the likelihood of catching HIV by at least 80% across the board.

This is important because up till now, to fuel claims like the Independent's 90% figure, PrEP advocates have had to pick their evidence carefully. Previous studies like the multi-country iPrEx study could point to subsets of participants who actually took PrEP as indicated and had at least that level of protection - 92% in the case of just the US participants, for instance, or 96% or more in men who took the drug at least four days a week.

So PrEP advocates could argue that it had great potential - but not that it had great actuality. PrEP's actual effectiveness in the latest version of iPrEx was just under 50%, and that's because not many more than half the trial subjects actually took it. Worse, a couple of studies in that most vulnerable group, young women in Africa, had shown no effectiveness, because only about a quarter of them took the pills. Maye PrEP was doomed, not because it didn't work, but because people just didn't want it.

This is certainly what Michael Weinstein, maverick director of the AIDS Healthcare Foundation in the US, has been saying. Vigorously opposed to PrEP, which he believes will be a "public health disaster", and equally in favour of condoms, he has been splashing ads all over US gay papers citing the actual effectiveness figures from PrEP trials.

But now we've shown that if you give PrEP to the right, motivated and prepared, gay men, they will take PrEP (both daily and intermittently) and it will work. Even more important, I think, is the fact that his finally nails the "PrEP won't be as safe as condoms" idea.

AHF have been running a companion ad saying that condoms "work 98% of the time if used consistently and correctly" and noting that 65% of adolescents use them. So let's run a thought experiment. Let's suppose PrEP was the standard way of preventing HIV and that we had just invented condoms and wanted to do a scientific trial of them. And why not? Condoms have many advantages: they're cheap, they don't have side effects bar the odd latex allergy, and they stop a lot of other STDs.

What would be their effectiveness?

Well, let's be generous and use the figure for the proportion of UK gay men who used condoms every time during 1994, this country's peak year for condom use: 68% (it's now more like 45%).

However condom efficacy is not 98%. That's under conditions of ideal use, and that means they never, ever break, slip off, leak, or are put on too late or removed too early. And they are certainly never whipped off surreptitiously in order to revive a flagging erection.

Researchers have a measure called 'typical use' which compares HIV infections in people who say they always use condoms with HIV infections in people who admit they don't. The result is that, because condoms are actually hard to use perfectly, their typical efficacy in anal sex is 70%. If we look at the highest-efficacy study in that composite result, we get 87%.

So, even in the best of all worlds, the kind of effectiveness you'd probably see if you gave gay men condoms who had never used them before, even if they achieved the highest historically-observed condom usage rates, is about 60% and would most likely be less.

You can still argue otherwise, but I think that's probably about the limits of what condoms can achieve in effectiveness. Compared with 80% for PrEP.

These studies demolish several assertions made by critics of PrEP. Firstly that condoms work better than PrEP. The don't. Secondly that people won't adhere to PrEP. They will. Thirdly that there will be a public health disaster if people switch from condoms to PrEP. There won't be.

Condoms will remain an important part of HIV prevention and probably the method used by many gay men; there will always be guys who prefer rubber to pills, as there are women to the contraceptive pill. One guy, a very literate gay health reporter, told me recently he'd always trust condoms more "because I can see them" and I think, no matter what the figures, that it will take a long time not just for the facts about PrEP to seep through the gay community (let alone get to non-gay people who might benefit) but for them to fully trust that it works.

The same has been true of the other side of the golden HIV prevention coin, that people with HIV who are on successful treatment are essentially non-infectious, and I expect only a slow growth in PrEP use because of this.

But, as with the contraceptive pill for women, I expect biomedical HIV prevention methods to come to predominate in the end. Condoms will always have a place, but I expect them to increasingly be used in the context in which they were traditionally used - in first sex, in first dates, in commercial sex, in casual sex - in any situation where you don't trust your partner not to have an STD.

Michael Weinstein got it exactly the wrong way round when he said Truvada was a "Party Drug" - it's condoms that are the additional, and traditional, precaution people will likely go on using in party sex. It'll be PrEP for the marriage bed, or at least the steady date.

The comparison with the contraceptive pill is useful in other ways. It aroused the same moral indignation. People worried about the side-effects, which were real and very occasionally fatal. It was widely forecast its use would lead to an increase in STDs - and that indeed happened in the 1970s, though rates were already falling before AIDS came along. Despite these disadvantages, only fundamentalists now argue that the Pill was anything other than a liberation for women and one of the catalysts of a social revolution.

So, it'll be a while before we see gay men using PrEP as their HIV prevention method of choice, and not only because of cultural resistance and a generational attachment to barrier-method sex. Even in the US where PrEP is already available (if you have a co-operative health insurer and can argue for it) it's only catching on slowly and in the UK, where the NHS has been caught on the hop by the PROUD results, it may not emerge from the NICE evidence-mincer till 2016. It may be that the 545 PROUD Men will be the only guys on PrEP for a while, though I personally think we should advocate for some open-label dispensation.

However what these studies prove, as opposed to just suggest, is that if gay men switched condoms for PrEP, or even better used both , we would see better control of HIV than we do now, not worse.

2015 may turn out to be for HIV prevention as 1996 did for treatment and 2001 for global access to treatment: the year it all changed. More study results - of a microbicide gel, of vaginal rings infused with HIV drugs and contraceptives for women, even of a PrEP drug that can be injected once a quarter - are coming along, some soon. And in 2016 we may see the start of human trials of an HIV vaccine that really does work.

Eventually the days when the one and only thing we had to protect ourselves from HIV was a piece of rubber will recede into the past.

  • Gus Cairns is co-chair of the PROUD trial.