Where next for HIV prevention?

Gus Cairns finds that UK HIV prevention campaigners and researchers are all in agreement that something has to change. They’re not so certain about where we go next, though.

The figures are stark. In much of the world, to quote Michel Sidibé, Executive Director of UNAIDS, “We have halted and begun to reverse the epidemic.”¹ But infections acquired in the UK are increasing, especially so in gay men who, for the first time in more than a decade, were diagnosed in larger numbers than heterosexuals diagnosed here but infected abroad.² Last year, there were more than 3000 new HIV diagnoses in gay men and other men who have sex with men, an 11% increase on the previous year.³

Most other sexually transmitted infections (STIs) are continuing to rise in gay men too, even though - for the first time in ages – the rate is steady or declining overall.⁴ In 2010, gonorrhoea cases were 3% higher in the general population than in 2009 but 33% higher in gay men: gonorrhoea is a good ‘indicator disease’ for the rate of unprotected casual sex in the population.

Infections among heterosexual people in the UK are also rising, and nearly as fast. But there are still only a third as many, and gay men run 50 to 100 times as much risk of HIV as heterosexual people.

This contrasts with the situation in some comparable parts of the world. HIV infections have plummeted in gay men in San Francisco over the last few years,⁵ and more recently there has been a large decline in HIV diagnoses in Washington, DC.⁶ HIV diagnoses have also gone down in British Columbia in Canada.⁷ These declines are attributed in the main to more people getting tested and put on treatment, though people reducing their risk behaviour after diagnosis may be a factor too.^8,9

In Europe, there are fewer successes to report, and in some countries with similar epidemics to the UK, such as the Netherlands, infections are also rising.

More choices

What’s to be done? There are a number of ways to bring down the HIV infection rate. Some, such as needle exchange and treating HIV-positive women during pregnancy, do not apply to sexually transmitted HIV. Some, such as post-exposure prophylaxis (PEP), have limited effect at a population level. And some, such as circumcision, may not make a big difference in the UK context where the majority of infections are in gay men (though it might be an option for straight men).

Other methods can be classed as:

• Traditional: condom provision plus counselling, support and campaigns to encourage people to have safer sex and use condoms.
• Promising: ‘treatment as prevention’ - increasing the number and frequency of HIV tests and putting as many diagnosed people as possible on treatment.
• Tested but not tried: Giving HIV-negative people HIV drugs, as in oral pre-exposure prophylaxis (PrEP) and microbicide gels.

In the last two categories, we have seen some exciting results in the last year or two; scientific trials found that:

• If HIV-positive people were on treatment there were 95% fewer transmissions to their partners (HPTN 052).
• In HIV-negative gay men who took a daily Truvada pill, the HIV infection rate was reduced by 43%; in those who reported taking 100% of their pills, this increased to 73% fewer HIV infections (iPrEx).
• In women using a vaginal microbicide gel containing tenofovir, the risk of HIV infection was reduced by 39% (CAPRISA 004).
• A candidate HIV vaccine reduced infections by 31%: not a wild success, but the first vaccine to show any efficacy in humans (RV144).
• And one important negative result: contrary to the iPrEx trial, oral Truvada did not reduce infections in women (FEM-PrEP).

There’s any number of ways of responding to these findings. In San Francisco, the public health department has opted to stop nearly all safer-sex campaigns and to put all the money into maximising testing and treating all people diagnosed, regardless of CD4 count.

In the UK, nothing as bold has been tried yet, although the new guidelines¹⁰ on safer sex about to be published by the British HIV Association (BHIVA) and the British Association for Sexual Health and HIV (BASHH) do take note of the implications of treatment as prevention (see Safer sex in the treatment era, HTU 204).

Although there’s general agreement that we need to make significant changes to HIV prevention in the UK, we are at the earliest days of agreeing on an effective strategy, which might include some of the above new options in a considered way but which, in the era of flatlined funding, would not require more money to be put in upfront.

A new strategy

Anthony Nardone is a consultant epidemiologist in the HIV/STI department of the Health Protection Agency, the national surveillance centre for infectious disease. He says:

“We were very disappointed when the 2010 HIV diagnosis figures appeared. Diagnoses in gay men had remained steady for a couple of years at about 2800 and we hoped to start seeing a real HIV treatment dividend; after all, 80% of diagnosed HIV-positive gay men in the UK are on treatment and 95% of those are virally suppressed. It was a sign we had to do something new.”

 In April, in collaboration with BHIVA and BASHH, the HPA proposed improvements in HIV prevention. We described their embryonic idea in HTU 206 (see The new prevention, May 2011). The idea was to roll out a so-called Intensive Combination Prevention (ICP) programme for gay men at high risk of HIV infection, attending larger genitourinary medicine (GUM) clinics in the UK. The three legs this strategy rested on would be:

1. An intensified system of offers of regular STI screening and HIV testing appointments.
2. Access to web- based health promotion and in-person behavioural interventions.
3. To the highest-risk men, the offer of daily Truvada as PrEP, initially only at a handful of clinics.

Have we tried hard enough?

Some people argue we’ve not been doing traditional HIV prevention properly in the UK, at least not for the last 10 or 15 years, saying we’ve never practised what’s been proven to work and we could promote safer sex a lot better. They’re also concerned that the newer, treatment-based approaches to prevention might make matters worse if the focus is taken off condom-based safer sex.

Peter Scott is a member of Status, a new group challenging the way HIV prevention for gay men has been done in the UK. He says that, unlike the US, the UK has only recently started to review the evidence for which traditional prevention methods actually work, and to programme them accordingly. He says:

“I like the ICP idea, and I can see how you could incorporate PrEP as a kind of salvage therapy when other measures have failed. But before you can compare ICP with ICP-plus-PrEP, you need to use the ‘combination prevention’ that works best. You wouldn’t compare a new drug in a trial with one chosen ‘because we think it works’. Yet this is essentially how prevention has operated in the UK.

“I recently did some consultancies with HIV agencies and asked them how they knew that what they did would lead to fewer cases of HIV. I met a lot of resistance: basically people said ‘We’re doing what we’re doing because it’s what we’ve always done’.”

The people who have been providing HIV prevention resources are similarly cautious about making radical changes like PrEP, but emphasise that as a sector it’s been difficult to form consensus about what success in HIV prevention looks like anyway.

Those providing existing HIV prevention programmes are cautiously welcoming of PrEP as part of a wider front of combination prevention.

Ben Tunstall is Terrence Higgins Trust’s Head of Health Improvement. He said: “A combination of prevention approaches is the way forward and there must be a backdrop of clear, consistent messaging on HIV and safer sex.

“We need to continue searching for, testing and evaluating new ways to tackle HIV but it’s vital we don’t throw the baby out with the bath water and drop what we can show is already working. It’s not one thing versus another; we need a broad front.”

Change needed, but what change?

Others are more sceptical about whether applying safer-sex programmes more rigorously would make a sufficiently big difference to HIV incidence. Sheena McCormack is clinical epidemiologist at the Clinical Trials Unit of the UK Medical Research Council, and a member of BHIVA. She says:

“There is very little robust evidence for behavioural interventions, but in part that’s because it’s difficult to assess these in a randomised controlled trial. Clearly, behaviour change had a dramatic impact on the epidemic in the period when HIV was a terminal disease, but now that HIV itself is less threatening we need to combine this with other methods.”

BHIVA and BASHH have been writing a position statement on what the iPrEx trial implies for the use of PrEP, triggering a much wider discussion on the HPA proposal, PrEP, and the future of HIV prevention in the UK. In the process, the UK PrEP Working eGroup has brought together clinicians, researchers, public health experts, commissioners, prevention promoters and gay and HIV activists, in probably the first attempt in the era of HIV treatment to bring together all UK prevention stakeholders.

Detecting the undiagnosed - and the not-yet-infected

As a result of discussions, a number of important changes were made to the proposed strategy. One set of questions asked from the start was: Who are these ‘high-risk’ people? Would targeting them be the best way to reduce HIV infections? And how do we go about assessing whether someone falls within this category without stigmatising them or scaring them off?

Dr Martin Fisher represents BASHH in the eGroup. As an HIV clinician in Brighton, he has supported a number of innovative testing programmes.

“We have known for some time that many, if not most, of the new infections are coming from undiagnosed people.¹¹ HPA data indicate that 24% of gay men who test positive have been infected in the last six months, compared with under 10% of heterosexuals. In under-25s that’s 35% and up to two years ago it was running at 50% in Brighton. That indicates continued high incidence and fast transmission between networks of gay men.

“So any strategy has to include both reducing the proportion of people already with HIV who are undiagnosed and the length of time they stay undiagnosed, and identifying the people who are most at risk of acquiring it in the next six months.

“There are signs of the beginning of a culture change in HIV testing in gay men – a much higher proportion have been tested at least once – but we need to get far more people testing regularly, as they have managed to do in the US and Australia.”

Identifying ‘high-risk’ people will be crucial to identifying who might benefit from the ICP programme and PrEP, but there is no standardised approach to this in the UK. Sheena McCormack, with others in the eGroup, shares the vision of an online self-assessment tool (tentatively titled My Risk, My Options) that could be adopted by GUM clinics and community-based organisations. This would ask people for brief details to create their risk profile for acquiring or transmitting HIV, suggest options available to alter this risk, and recommend resources for more information. For it to work successfully, they would need to permit the data to be shared with a named professional – probably their GUM consultant. Resources would have to be flexible to reflect what local clinics can offer: for instance, some clinics already offer motivational interviewing-based safer-sex counselling, but most don’t.

A trial of PrEP

In the original plan, half the clinics would have offered PrEP to the highest-risk people – basically, gay men having unprotected receptive anal sex. However, feedback from STI clinicians and the eGroup convinced the team that PrEP should still only be offered as part of a clinical trial.

McCormack says: “We don’t know whether people will change their behaviour if they know they’re getting PrEP.”

On the one hand, one of the explanations for the low rates of adherence seen in the iPrEx trial - probably no more than 50% overall - was that people knew there was a 50/50 chance they were taking a placebo. They might be more motivated to take PrEP if they knew they were taking Truvada.

On the other hand, if they know they are taking PrEP, will their condom usage plummet, even leading to increased transmission? And if they can’t consistently use condoms, will they be able to stick at taking PrEP?

“Only a randomised but open-label trial will answer these questions,” says Sheena. “Offering it as part of a trial would also make it possible to offer experimental regimens such as intermittent dosing or taking it only before sex, or before and after sex. In addition, there are regular opportunities to apply for funding for trials, whereas it’s not clear where new funds could be found for HIV prevention in the current economic climate.”

The idea now is to try to develop My Risk, My Options over the next year, while the protocol and funding for the PrEP trial are being confirmed. If successful, it may be possible to use the tool to collect necessary information to complement the public health systems and the trial. The trial’s design would randomise participants to an immediate or deferred offer of PrEP; everyone would be seen in clinic at key intervals for HIV and STI testing, and other services such as established behavioural interventions.

Some big questions

Many more questions remain unanswered about the feasibility of the strategy and the sheer complexity of bringing its different strands together.

One is whether people will use the web-based self-assessment tool. The idea is that anyone presenting for an HIV test would be asked to fill in their initial risk assessment at a terminal at the clinic, but will they continue to do this when they get home? HIV prevention from the last 15 years is littered with the corpses of innovative internet resources for people at risk.

One health promotion worker who works with gay men commented: “Positive people share an interest and will use an online resource, but there isn’t really a community of the HIV-negative as such, and it’s hard to get them engaged. No one really identifies as a 'risk taker' anyway: denial is a powerful thing.”

Not everyone will want to use a self-assessment tool, share the results with their doctor, or have the computer savvy to do so. The challenge, therefore, will be to get community buy-in for this strategy and publicise it widely, which is why involving as big a coalition of stakeholders as possible is important.

Should we restrict the tool and the subsequent offer of PrEP to gay men? Anthony Nardone feels that, for now, we should.

“This is intended to tackle HIV transmission in the highest-risk population in the UK,” he says. “To adapt it to other populations would need a larger survey with different questions. It would be great to do that if it works, but right now the cost may not be justified.

“Its other purpose is to gain demographic information in advance of a study of PrEP, and so far we only have proof that oral PrEP works in gay men.”

Sheena McCormack feels it would be a waste to restrict My Risk, My Options to gay men who turn up with STIs.

“It could be on offer in a whole variety of places,” she says, “as the UK’s standardised sexual risk-assessment tool. It could be used in a whole number of different settings, by everyone from the ‘high risk’ to the ‘worried well’.” By concentrating solely on gay men, would the programme miss out on detecting the small, but growing, number of highly at-risk heterosexuals?

Why not just put all the resources into testing people for HIV and treating all those diagnosed? This is what happened in San Francisco.

Anthony Nardone says: “Treatment as prevention is very much part of the equation, but if you just concentrate on people who are already HIV-positive you take away the responsibility from HIV-negative people to keep themselves safe, and also the power to keep themselves safe.

“If you are someone who is HIV-negative but is highly at-risk – for instance, because you’re the receptive partner in anal sex – what’s on offer for you? ‘Wait till you catch HIV, then we’ll treat you’ is very disempowering.”

Where's the money?

The biggest unanswered question about all this is where the money will come from. The HPA has already had to scale its PrEP ambitions down – though it still aims for about 5000 men to end up being offered PrEP – and GUM clinicians have been telling BHIVA that they couldn’t possibly cater for regular six-monthly checks for a high proportion of their patients.

“This is the right time to invest in HIV prevention with new biomedical interventions being added to behavioural ones, but a bad time for the government, and especially the NHS, to have to find new money,” says Sheena McCormack. “Over the next year at least, people in the NHS will be preoccupied with the reorganisation, so it seems likely to be a year before any opportunities will arise for new initiatives.”

In some ways, this may not be a bad thing: it allows a year’s breathing space in which a coalition of prevention stakeholders can formulate a really well-thought-out strategy to hit the funders with.

In other ways, it’s a disaster. No one is disagreeing with the HPA’s estimate that there will be 100,000 people with HIV in the UK by 2013.

There is one wild card: Lord Fowler, acknowledged as the architect of the UK’s original HIV prevention strategy. If he, and the House of Lords committee he is chairing to review the state of HIV in the UK (see Keith Alcorn’s article, Talking to the Lords), are as shocked with the current state of affairs as the prevention experts, there’s a chance the coalition government may reverse the underfunding of HIV prevention. If not, we are set to have one of the highest HIV infection rates in any high-income country, which would impose a crippling cost burden on the NHS.

Martin Fisher ponders: “PrEP and intensive prevention may be cost-effective, but are they affordable?” Equally, in the longer term, will the UK pay the price of not affording them?

New from NAM: Preventing HIV

New online on aidsmap is the third edition of Preventing HIV, NAM’s comprehensive and detailed summary of the history of, and evidence for, methods of preventing HIV ranging from condoms and sexual abstinence to the latest news on microbicides and PrEP (and a summary of the progress towards a vaccine online soon).

See www.aidsmap.com/resources/Preventing-HIV/page/1412415/