A jagged little pill: are we prepared for PrEP?

Pre-exposure prophylaxis (PrEP) is the idea of taking HIV drugs in order to avoid being infected with HIV in the first place. We might know if it works within the next year. We need to start thinking now about how it will be made available, says Keith Alcorn.

By the end of next year we may have the results from the first large studies of pre-exposure prophylaxis. The first study is due to report by the end of this year, and at least one more is likely to report by the end of 2010. They are looking at how well a daily dose of the HIV drug tenofovir will prevent HIV infection in gay men in the United States and in injecting drug users in Thailand.

It’s possible neither study will produce a clear-cut result. We will then need to wait for results from the larger, longer studies using tenofovir plus FTC (Truvada), whose results are due in 2010-12, before we know if it works and who for. These studies, supported by the US Centers for Disease Control and the Bill and Melinda Gates Foundation, are looking at gay men, women and HIV-discordant heterosexual couples, so cover every significant route of infection in adults.

What if the tenofovir-only studies show this drug alone has some protective effect? If that happens, we may have to consider how PrEP should be implemented much sooner than expected.

This may raise some thorny issues. Although the results from one trial will probably not change international public health policy, gay men in particular might begin to adopt PrEP informally if they hear of positive results from the first trials.

At the moment there’s little evidence that tenofovir or Truvada are being used systematically as PrEP by gay men in the UK, although we interview one man who does in this issue. But US gay newspapers have reported the informal use of tenofovir in several large cities, and one HIV physician at least, Marcus Conant of San Francisco, has gone on record to say he has prescribed it to some gay male patients.¹

Awareness of PrEP is still low in the UK, but in fact PrEP is already being used here, to assist in risk reduction when HIV-discordant partners are trying to conceive. Dr Stephen Taylor of Birmingham’s Heartlands Hospital told HTU that his hospital has been providing drugs for pre-exposure prophylaxis to partners of patients, and Swiss researchers in 2007 successfully used two doses of PrEP to protect HIV-negative women trying to conceive with HIV-positive men. But these women’s partners had undetectable viral loads and they only had unprotected sex on the days when the woman was most likely to conceive. The risks some people run are far greater.

Dr Mike Youle of the Royal Free Hospital in London says that taking the drugs when sex is anticipated, rather than every day, is the way that most people are likely to use PrEP. He is currently exploring ways of raising money outside the usual funding mechanisms for a European trial of intermittent PrEP, which he says will be critical to proving the concept.

This idea was explored by a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in February,² which showed that in monkeys recently exposed to HIV, a dose of Truvada given one to three days before exposure led to a 15-fold reduction in infection rates, whereas dosing just two hours beforehand provided only fourfold protection. However the animals also received another dose of the drugs two hours after exposure, so it wasn’t a pure PrEP trial.

The big unknowns are whether people who become infected despite PrEP will develop resistance as a result, and whether there might be long-term side-effects. People with HIV will generally tolerate some side-effects in exchange for effective treatment of an otherwise life-threatening condition. HIV-negative people may be much less willing to tolerate even minor side-effects to guard against infections that might not have happened anyway. Drug licensing authorities will also be less forgiving.

The question of expectations goes to the heart of a major uncertainty about PrEP: will people consider themselves at enough risk to use it? Research has consistently shown that a substantial proportion of gay men have unprotected anal intercourse with partners whose status they assume on the basis of guesswork, as a German study presented at CROI showed.³

The 2006 Gay Men’s Sex Survey⁴ found 53% of the 12,155 gay men responding had unprotected anal intercourse at least once in the previous year, compared with 49% in the 2005 survey. It’s clear that current HIV prevention activities are failing to persuade large numbers of gay men to use condoms in order to avoid HIV infection, and have been failing to do so for many years.

If PrEP was available, it might protect all those men who have trouble using condoms consistently, who have high numbers of sexual partners or who have HIV-positive partners. But it could also introduce another layer of complexity to decision-making about condom use, and another opportunity to make vague assumptions about whether someone is positive or not, or at risk or not.

On the other hand it might conceivably reduce stigma, shifting the onus of status disclosure away from the positive person and towards equal negotiation.

PrEP might also have the potential to increase uptake of HIV testing, and the frequency of testing. If gay men knew they had an extra layer of protection against HIV that was only obtainable from a clinic they might test more frequently, might make fewer assumptions about their own and their partners’ HIV status, and might talk more about their status with partners.

How would it be delivered?

Initially PrEP would probably have to be prescribed through sexual health clinics, accompanied by regular HIV testing. But some advocates want the drugs with the best safety records eventually to be available over the counter. This approach would shift the cost of providing PrEP to the user, making it more affordable to the NHS in the long term.

The short-term cost of PrEP could be enormous at current drug prices, but its cost needs to be considered in the context of the long-term cost of 7000-plus new people with HIV per year in the UK, each of them requiring antiretroviral therapy for 20 to 40 years or so at an annual cost of £10,000 a year for drugs and care.

The greatest impact on new infections would probably come from targeting PrEP to men with histories of serial risk-taking and repeat testing, to HIV-negative gay men with a high number of sexual partners, and to HIV-negative men and women in HIV-discordant relationships, especially women seeking to conceive. Most doctors working in sexual health clinics already know of some people who would fit this category and would benefit greatly from an alternative or additional intervention to condoms.

The Department of Health has already instructed NHS trusts to offer post-exposure prophylaxis (PEP), which – in theory - should now be available from clinics and A&E departments to people after a high-risk sexual exposure But in practice, obtaining PEP is a lottery depending on where you live, who you speak to and whether you or your partner know enough about your entitlement to demand it. Given the evidence that some healthcare workers are still reluctant to offer PEP to people who have taken risks, what are the chances of their offering PrEP to people who are thinking of taking a risk?

Given the current rate of new infections, and the potential long-term unsustainability of treating ever-growing numbers of people with HIV infection, there needs to be serious consideration of how PrEP might be made available in the UK. Condoms were never designed to be used as a lifelong protection measure and their limitations as a prevention method are evident from the steady rate of new infections. Maybe people are entitled to something more.

The morning-before pill

HTU talks to one man who takes PrEP

Paul, 44, works as a scientific liaison officer and is a gay man who keeps himself well informed about HIV. He has been using PrEP as protection against HIV during sex for the last six years and so far has remained negative. He talked to HTU about why he started, how he does it, and how he thinks it could be used.

HTU: So how did you start using it?

I met my partner James in 2003. I came out during the ‘Don’t die of ignorance’ campaigns in the late 1980s and was very scared of HIV, but then I fell in love with someone who happened to have it.

From the start the sex we had was very different from what I’d experienced with anyone else. It was more intense and intimate and also rougher – we’re both into S&M and fisting. He was very open about being positive and having an undetectable viral load and also about not liking condoms. Before that I’d had 20 years of safer sex but I felt ‘I’d really like to know what it’s like to be that intimate’.

So I thought: What about PrEP? My job had involved reading up on the animal studies. I knew we were likely to have sex every weekend so post-exposure prophylaxis, PEP, wasn’t the answer.

How do you use it – and how do you get it?

I use my partner’s pills. We don’t have sex so often that his clinic is likely to notice; in fact these days after six years it’s down to about, say, once every two months.

I used tenofovir then switched to Truvada when he did. I take one dose about two hours before sex then another 24 hours after sex and a third 24 hours after that. We always plan sex because we’re into quite rough stuff so I always know when we’re going to. I don’t think I’ve had any side-effects; I got a slight headache after one Truvada dose but it might just as well have been caused by poppers!

Did you have any reservations about taking it?

Oh yes, loads. I felt guilty about barebacking anyway: why should a reasonably intelligent person like me put themselves at risk of a life-threatening infection? I went to counselling, hoping it would make me see clearly what I was doing. But instead it just reinforced my decision about the level of risk I was happy with. Having had intimate bareback sex with my partner, it just felt like this dispiriting retrograde step to start using condoms again.

In the end I think the PrEP, as well as hopefully adding more protection, helped me live better with the guilt of not using condoms. It helped me feel I was doing as much as possible to reduce my risk.

Do you test regularly? And would you use PrEP if your partner had a detectable viral load?

Yes, I test every six months and so far I’m still negative. HIV isn’t that easy to catch and it could just be luck, of course. I’m quite prepared for that positive HIV test and I don’t think either of us will have a drama. But I’m not going to relax PrEP because it’s much better not to have HIV than to have it. James is pleased I’m taking it.

My partner’s 100% adherent and has always been undetectable, but we both do play outside the relationship sometimes and on a couple of occasions I have used it with HIV-positive guys who were not on treatment. I’ve asked them not to cum in me, though I’ve heard that doesn’t make a lot of difference. With HIV-positive guys we always negotiate and they play to my level of safety or me to theirs, whichever is safer.

Even if we use condoms I will take PrEP. With the kind of sex I like, there’s plenty of other transmission risks even if you do use condoms. I’m amazed at how guys will use condoms but quite happily share pots of lube, for instance.

These days I’m almost a ‘reverse serosorter’: I’d rather have sex with an HIV-positive guy who knows he’s undetectable than a guy whose last test was negative but could be coming down with HIV and have a really high viral load.

Do you still have doubts about it?

Well, the obvious thing is that it doesn’t protect you against other STIs [sexually transmitted infections]. In fact I have caught an STI and had to get treatment for it. Since then we’ve really tightened up on other precautions like not sharing lubes.

It’s not me really, however, who’s had doubts about it. My GUM clinic was concerned I was using it as a method of preventing HIV infection, and still [is]. Rightly so in a way, as the evidence is still in its infancy. But I haven’t exactly felt 100% supported in my decision and they keep on wanting me to talk it over with the health adviser.

The other concern is worry that they’ll restrict it to heterosexual serodiscordant couples who are trying to conceive. Just because gay men’s sex doesn’t involve procreation, why should we be penalised?

If the current trials prove it works, who do you think should get it, and how?

I think initially people in serodiscordant relationships should get it – even if they use condoms. They should be willing to have counselling and contemplate behaviour change; clinics might worry about being pressured to provide it if it works and won’t want to be seen to condone unsafe sex. Maybe the clinic could see it as a ‘stopgap’ pending other behaviour change. However I think it’s important not to use behaviour change as a condition. Secondly, I think it would be useful for clinics to identify people at high risk who are having problems with condom use: maybe the doctor and the health adviser could review patients together. Then it might be suggested as part of the solution.

Any last words?

PrEP has helped me tackle my fear of HIV and my guilt at barebacking. I’m in a wonderful relationship and am very happy with the sex I’m having. I didn’t want fear of HIV to affect that and PrEP fell naturally into place as a strategy. I only hope that the studies show it to be effective and that I haven’t just been lucky so far.