PrEP: Discussion Paper On 25 August 2015, HIV Scotland will bring together key stakeholders to discuss the current and future use of PrEP in Scotland. This discussion paper has been created in advance of this to provide an update on PrEP, answer some common questions about it, and highlight issues for consideration. You can also see examples of what community and workers are currently telling us about PrEP use in Scotland. What is PrEP? PrEP stands for Pre Exposure Prophylaxis, and is an HIV prevention strategy that uses antiretroviral (ARV) drugs to protect HIV negative people from HIV infection. It usually involves someone known to be HIV negative taking ARV drugs on a daily basis. This most commonly entails the ARV drug Truvada, which is already licensed for use in Scotland to suppress the HIV virus in people living with HIV. PrEP does not prevent other sexually transmitted infections and is therefore intended to be used in combination with other preventative methods, such as condoms. Is PrEP effective? PrEP, when used as prescribed, has proven in clinical trials to be highly effective at stopping HIV transmission. Two recent trails - IPERGAY and PROUD - examined the potential of PrEP to prevent HIV transmission, with each study focusing on a different type of PrEP regime (as described below). Both studies reported an 86% reduction in HIV transmission amongst people using PrEP when compared to those who were not. The PROUD study, in particular, provides a valuable insight into how PrEP may be used in ‘real world’ situations, as all participants were aware they were on PrEP and so could make informed decisions about their sexual activities accordingly while participating in the study. The PROUD study The PROUD study measured the effectiveness of daily PrEP for gay and other men who have sex with men. It was designed to see if the drug used in the trial - Truvada - would reduce the incidence of HIV infection in a ‘real world situation’ where participants knew they were taking an active drug as PrEP. It aimed to address questions such as whether taking PrEP would change sexual risk behaviour and whether or not it would be cost-effective to make it available on the NHS. The study launched in 2012, enrolling 545 participants at 13 sexual health clinics in England. The study randomised participants to receive PrEP immediately or to receive PrEP after a period of 12 months, allowing researchers to compare those on PrEP versus those not yet on PrEP. Participants selected to take PrEP were given a regular three month course of Truvada and asked to take one pill per day. In the study there were 1.3 new infections per 100 person-years in the group given PrEP immediately, and 8.9 per 100 person-years in the group who were not yet on PrEP. Adherence to the daily drug regimen appeared high in the study, and there was no difference in the number of men diagnosed with other STIs between those on PrEP and those not on PrEP. The

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86% protection from daily PrEP reported by the study was the highest reported from any randomised controlled trial of PrEP at the time of reporting. 1 The IPERGAY trial The IPERGAY trial measured the efficacy of taking PrEP before and after sex rather than daily, as in previous PrEP studies. Study participants were randomly assigned to one of two groups. Men in one group received Truvada pills (PrEP group) while those in the other group received placebo pills (placebo group). Participants were not informed which group they were in. The randomized, placebo-controlled study began in February 2012 and was stopped by an independent data safety review board in October 2014 because of high efficacy. At that point, 400 participants had been enrolled. The data safety and monitoring board found a "very significant" reduction in the risk of HIV infection in the group of participants using as PrEP compared to the placebo group. The monitoring board subsequently recommended that the placebo group be stopped and that all trial participants should be offered Truvada as PrEP. IPERGAY was the first study to demonstrate that event driven regimens were effective for HIV prevention amongst men who have sex with men. In addition, the IPERGAY study provided evidence for a less expensive and more flexible way to use PrEP while maintaining high efficacy. The study showed that participants were capable of taking PrEP in a way that suited their lifestyle and maximized their safety, if offered the chance to do so. Although a number of studies have found oral PrEP to be highly effective for men who have sex with men, there is less evidence available to demonstrate how effective PrEP may be for other groups who may be at high risk of HIV, or for heterosexual men and women. What is the current situation in Scotland? HIV Scotland has been asking community about their experiences of PrEP. People have told us that PrEP is currently being talked about, requested and used in Scotland. Some people are obtaining Truvada from friends who are prescribed it as treatment, others have accessed emergency PEP prescriptions with the intention of taking this as PrEP, while others are purchasing Truvada online from private retailers. In the UK, the PrEP drug, Truvada, is currently only officially licensed as a combination antiretroviral treatment, and not for prevention. All medicines in Scotland have to be approved for use by the Scottish Medicines Consortium (SMC). The SMC will only consider a drug for a change in indication once the manufacturer receives a marketing authorisation (licence) for the new indication from either the European Medicines Agency (EMA) or Medicines and Healthcare products Regulatory Agency (MHRA). As yet, relevant pharmaceutical manufacturers of PrEP candidates have not made an application for such approval. However, individual clinicians can currently prescribe PrEP ‘off-licence’. This allows clinicians to prescribe a medicine for treatment outside its licensed use, but requires that they take individual responsibility for doing so.

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The Proud Study – Study Results: http://www.proud.mrc.ac.uk/news/study_results.aspx

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What are the debates about the use of PrEP in Scotland? There have been some important debates around the possible use of PrEP, and concerns which remain to be addressed if the opportunities it presents are to be realised. In particular, current debate is focused on questions of: cost effectiveness; who should access PrEP and how; how to ensure the safe and effective use of PrEP; and, how to avoid an increase in risk taking behaviors. Cost effectiveness Much of the current debate over PrEP is focused on its cost effectiveness, with people asking whether its cost is justified, or whether this money could be better spent funding other prevention interventions. While the exact cost of providing PrEP in Scotland remains unclear, there is growing evidence that PrEP is cost-effective in preventing high-risk individuals from getting HIV. In addition, PrEP is currently available to purchase privately but its price creates significant inequalities in terms of access - between affluent individuals who can afford it and those who cannot (a one month supply of Truvada, privately purchased, costs approximately £400-£450). 2 • • • •

How can we ensure that all those who are at high risk of HIV infection can access PrEP, also accounting for cost implications? What research is needed to better assess the cost-effectiveness of PrEP within a Scottish context? How might the availability of (significantly cheaper) generic ARVs in Scotland impact on this debate? Could ‘event driven’ regimens of PrEP offer a solution?

Access to PrEP Connected to discussion over the cost effectiveness of PrEP, are questions relating to who may stand to benefit most from it and how access should be determined. Men who have sex with men continue to be most at risk of HIV infection in Scotland, suggesting that existing prevention methods are failing to meet the needs of all of this group. Based on the evidence that PrEP is an effective prevention method for men who have sex with men, WHO has now recommended that PrEP be offered to this group as an additional HIV prevention choice. 3 However, there are other groups and individuals in Scotland who could also benefit from PrEP and request to access it. • • •

Who might benefit most from PrEP in Scotland? What information do the public need about accessing PrEP a) now b) in the future? What is needed to support clinicians when making decisions about access a) now b) in the future?

Safe use of PrEP Adherence is a key component in PrEP effectiveness. In both the IPERGAY and PROUD trial, the only participants that became HIV positive while on PrEP had failed to take the recommended dosage of Truvada. It will be vital that anyone using PrEP understands how to use it effectively, regardless of whether it is obtained by prescription or privately purchased. 2

Figures based on those within the 56 Dean Street, Get PrEP, program.

WHO, Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations, July 2014

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What information and messaging is needed to ensure people know how to use PrEP effectively?

Changing sexual behaviours Concerns have been raised that PrEP will encourage unsafe sex practices, and increase the amount of STIs by reducing condom use. In the IPERGAY and PROUD study, sexual behaviour among participants did not change. There were still reported high rates of condomless anal sex and contractions of STIs, but taking PrEP did not result in an increase in risky behaviour. It is also the case that some people do not choose to wear condoms, even if they know they should use them or would like to use them. PrEP will also protect people when condoms break or slip off. However, it will be critical that people understand that PrEP is not intended as a replacement for condoms, but as an additional layer of protection. • •

What public health messaging is need about PrEP and risk reduction? What information and resources do workers need about PrEP?

Based on all of the above, HIV Scotland invites you to discuss the following issues at our roundtable on 25th August: How can we maximise the opportunities and minimise the risks of prescribing PrEP in Scotland? • How can we identify who might benefit from PrEP, and ensure that all those at high risk of HIV infection can access it? • What public messaging and information is required? • What resources are needed for clinicians? • What could/should be done now e.g. encouraging prescribing off label, developing resources etc.?

If you have any questions or input you would like to share about PrEP, please get in touch with us by calling 0131558 3713 or emailing [email protected].

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What you’re currently saying about PrEP… Community:

“People are selling their Truvada as PrEP. In 2015, two people have asked me to sell mine, they knew my status and they wanted to buy the box. I used to get prescriptions of Truvada six months in advance. Now the hospital are much more cautious.” “You hear it on the scene occasionally people talking discreetly about Truvada: ‘where can I get it?’ They tell you to ‘go to the clinic, give false postcode, false name and you will get PEP straight away. You can keep going back.’” “I know I have a lot of risky sex, I can't help myself, when knowing the risks I still do bareback. I guess I'm lucky for now to still be negative but if PrEP doesn't get released in the UK soon then I might end up catching HIV.” “It needs to be released now to help prevent more cases in the UK, I'm probably just one in thousands in the UK that PrEP would help protect my health.” “I have asked for PrEP at a clinic in Glasgow and was told it’s not available in Scotland.” “I was in a serodiscordant relationship when I got HIV. I went to get PEP one time. When the month of tablets had finished, I went back to see if I could get PrEP but they said ‘no you can’t get it’. If I had been able to get PrEP, I probably wouldn’t have got HIV, it’s just really sad.” Workers:

“As a doctor I have in mind obvious cases I have seen in the past to whom I would have given PrEP had it been available. But what do I do if a patient comes in and says ‘Please give me PrEP’ but he seems not to have the risks that tick my boxes? I can’t really say ‘come back with gonorrhoea and then we’ll talk about it’.” “There is a discussion to have about a universal switch to generics which could realise substantial savings which could potentially be used to fund PrEP.” “I would like to discuss how we can influence the national bodies for funding and trialling of PrEP in Scotland for high risk groups.” “My question would be around cost-effectiveness in lower prevalence areas. The PROUD study reported a number needed to treat (NNT) of 13. However the study was largely conducted in very high prevalence areas.” “How do we decide who's eligible and what would be the best way to supply PREP to this group?” “My only reference point is seeing PrEP talked about on the apps - one guy said he was taking it but this was (and I quote) ‘not an invitation to bareback though’ which I think sums up the problem perfectly.”

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