key: cord-0060239-5u4iyfuw
authors: Jaspal, Rusi; Bayley, Jake
title: HIV Prevention
date: 2020-10-30
journal: HIV and Gay Men
DOI: 10.1007/978-981-15-7226-5_4
sha: e712788c579a5644571d4add2bef0b3794bc2e5a
doc_id: 60239
cord_uid: 5u4iyfuw

In the absence of a vaccine or cure, prevention remains the most effective strategy against HIV. In this chapter, a variety of the prevention tools available to, and utilised by, gay men are reviewed. The long-standing policy of condom use is discussed, and the potential shortcomings of a prevention policy based exclusively on condom use are outlined. This chapter also considers alternative prevention approaches deployed by some gay men, such as ‘serosorting’ and strategic sexual positioning. The importance of both HIV and STI testing as part of effective HIV prevention is illustrated. Furthermore, key developments in HIV prevention, such as post-exposure prophylaxis, pre-exposure prophylaxis and treatment as prevention, are examined. Emerging prevention approaches, such as the use of microbicides and male circumcision, as well as the quest for an HIV vaccine are outlined. In this chapter, it is argued that all of these approaches have merits, that none is without its shortcomings and, therefore, that ‘combination prevention’ is key to eliminating HIV transmissions.

present chapter focuses on this very question-how can HIV be prevented among gay men at risk of infection?

In order to understand HIV prevention among gay men in the UK, it is helpful to look at HIV in a global context. Globally, the tide does appear to be turning with a steady reduction in AIDS-related deaths over the last decade. In 2004, there were 1.7 million deaths, in 2010 the figure reduced to 1.2 million, and in 2018 to 770,000-this represents a 50% reduction in AIDS-related mortality in under 15 years. 1 This dramatic reduction can be attributed in part to better public health initiatives, improved HIV education programmes, increased awareness and understanding of HIV and its transmission routes in populations at risk and, crucially, the significant expansion of HIV treatment (including among pregnant women living with HIV). There must be effective knowledge exchange, with collaboration between governments, global health organisations and charities for prevention initiatives to work at a local level and to be sustainable. In the UK, the aim is to stop new HIV infections by 2030-an ambitious goal that is achievable now that the government has committed to implementing the recommendations of the HIV Commission (led by the Terrence Higgins Trust and the National AIDS Trust), utilising the expertise of clinicians and researchers, and working collaboratively with third-sector and voluntary organisations as well as key communities affected by HIV.

The history of HIV was outlined in Chap. 2. Here we consider the history of HIV prevention, in particular, focusing on the early efforts to control the spread of the virus. The initial responses to HIV in many Western countries were actually led by community groups which formed in response to the perceived lack of a coordinated institutional response to the growing epidemic. As described in Chap. 2, the Terrence Higgins Trust, one of the most significant UK charities focusing on HIV, later transformed into a charity with political lobbying, health advocacy and social support for those living with HIV. In conjunction with the Lesbian and Gay Switchboard and later the National AIDS Trust, they produced the first public health campaigns to prevent HIV in the UK with funding from the government.

Many of the earliest educational pamphlets from community organisations in the UK drew upon material from the Gay Men's Health Crisis organisation in the US. Other community groups across the globe also began to promote the use of condoms and to advocate reducing one's number of sexual partners. The 'Play Fair' leaflet released in 1982 by the Sisters of Perpetual Indulgence in San Francisco is a good example of the very first public health campaigns, aimed at educating and reducing anxiety within the gay community by giving direct and practical instructions on how to reduce risk by having sex with fewer partners. However, some gay community groups saw this as a curtailment of their recently hardwon civil rights and were opposed to advocating the use of condoms and to limiting one's number of sexual partners.

Initially, the US led the way in advocacy, with the original efforts originating from San Francisco and New York, two of the worst affected cities in the early phase of the AIDS crisis. It was to take until 1987 for the global community to take action when the World Health Organization (WHO) formulated the Global Program for AIDS which attempted to work with community groups and activists in a coordinated way for the first time. The central tenet of the programme was education for people in highly affected areas. Condom promotion was seen as the most important intervention as physical barrier methods had been shown to be effective in reducing HIV transmission. Recommendations for blood donations and needle exchange programmes were also put forward to support other at-risk groups.

A major impediment to HIV prevention at the time came in the form of growing 'anti-gay' sentiment in the UK. In 1987, the British Social Attitudes Survey demonstrated that three in four people viewed homosexual activity as 'always or mostly wrong', while only one in ten thought that it was never wrong. 2 Furthermore, Margaret Thatcher's government introduced Section 28, a hugely damaging piece of legislation which served not only to reinforce the prevailing anti-gay sentiment at both social and institutional levels but also to decrease social support for young gay men. Its purpose was to forbid local authorities, who oversaw schools in the UK, to 'intentionally promote homosexuality or publish material with the intention of promoting homosexuality'. This legislation reinforced the stigmatising societal belief that homosexuality was chosen, could be encouraged and, thus, implicitly that it could be changed. Moreover, Section 28 caused confusion in local authorities and schools about what actually constituted 'intentional promotion', and, therefore, many simply avoided any acknowledgement of sexual diversity to the detriment of millions of young people growing up in the UK. Needless to say, this resulted in silence about many of the issues known to be related to HIV risk-safer sex knowledge, identity, psychological wellbeing and others (see Chap. 1). Until the repeal of Section 28 in 2003, the educational strand of HIV prevention policy was incapacitated, and it became virtually impossible to equip young gay men with knowledge about the dangers of HIV and how they might protect themselves.

On a more positive note, long-term projects overseen by nongovernmental organisations (and the WHO) have sought to de-politicise HIV/AIDS and to exert pressure on governments to take action and to support those most at risk of infection. For instance, the Global Program for AIDS went through many iterations firstly in 1996 to UNAIDS and was even discussed at the UN General Assembly 'Declaration of Commitment' in 2001, the first time a health issue had been scrutinised at a security council meeting. Furthermore, in 2003, there was a significant global development-the US President's Emergency Plan for AIDS Relief came into force, injecting $15 billion into HIV prevention over the next five years. The main objective was to increase access to HIV prevention in developing countries with the ABC method-Abstinence, Be faithful, Condoms. This narrow view of HIV prevention did not resonate with many at-risk groups, but countries welcomed the extra funding to bring their local epidemics under control. The fund transformed into the Global Fund to Fight AIDS, TB and Malaria, which now provides $4 billion per year in over 100 countries globally. It is believed to have saved 32 million lives, and of the 23 million people taking ART globally, 19 million are funded through this channel. 3

Over the years, there has been a sustained focus on HIV prevention, which includes promoting condom use, increased HIV and STI testing, the use of PEP and PrEP, TasP and less common approaches, such as the use of microbicides and circumcision as prevention strategies. Alongside the promotion of a combination of these prevention tools, the search for an HIV vaccine has continued. In the remainder of this chapter, we consider each of these methods in turn and look at how they have impacted and shaped the HIV epidemic in gay men.

Condoms are a highly effective approach to preventing HIV and other STIs. However, their efficacy is determined, in large part, by correct and consistent usage. Accordingly, condom education constitutes a significant component of sexual health promotion globally-in various contexts, people are introduced to condoms, informed about how they can be used effectively and, in some cases, how they can be 'eroticised' so that the pleasure of sex is not in any way diminished (Shernoff, 2006) . Although there has been a consistent emphasis on condom use in HIV prevention campaigns-a focus which remains even today-condom use among gay men has been decreasing over the last decade. There are several contributing factors to this behavioural decline-gay men may feel unable to negotiate their condom use in certain situations, face social pressures to engage in condomless sex, have impaired risk appraisal when using alcohol or substances in sexualised settings, experience erectile dysfunction and perceive a lack of 'closeness' or intimacy and reduced pleasure when condoms are used. The possible barriers to condom use were discussed in more detail in Chap. 3. A significant longitudinal study has examined condom use among over 5000 gay men in 21 cities in the US between 2005 and 2014. Paz- Bailey et al. (2016) revealed a significant increase in condomless anal sex acts. There was a 12.3% increase among those living with HIV (34.2% in 2005 HIV (34.2% in to 44.5% in 2014 and an increase of 11.8% among those who reported being HIV-negative (28.7% in 2005 HIV-negative (28.7% in to 40.5% in 2014 . The most significant increase in condomless anal sex was detected in those aged 18-24 years, suggesting that this age group may be particularly vulnerable to HIV infection and, thus, should be a key focus of condom promotion interventions. Overall, numerous trials have shown that consistent condom use in gay men ranges from 40% to 60% (Leichliter, Haderxhanaj, Chesson, & Aral, 2013) with the latest data from a large sample of over 127,000 gay men in Europe indicating that only 40% of participants reported consistent condom use and that 10% reported never using condoms (Weatherburn et al., 2019) .

Those gay men who do not use condoms consistently may attempt to adapt their sexual behaviour in order to reduce their risk of HIV infection. Some engage in the strategy of 'strategic positioning' whereby condoms are used only for those sex acts which are believed to be high risk. Receptive anal sex is by far the riskiest sex act with a 1-3% chance of acquiring HIV if the active partner has a detectable HIV viral load; and if the active (or insertive) partner is HIV-negative with an HIV-positive passive partner, the risk is much lower-around 0.1% (Cresswell et al., 2016) . There are many other variables which affect the level of risk, such as whether or not the HIV-negative partner is circumcised, the viral load of the HIV-positive partner, bleeding caused during sex and many others. Yet, the perception of risk may be low and, thus, condoms may not be used.

Furthermore, some gay men engage in the practice of 'serosorting' which refers to the selection of sexual partners based on their perceived HIV status. This means that an HIV-negative individual will have sex only with an individual whom they believe also to be HIV-negative. How one reaches this conclusion is another interesting question-some people assume that their partner is HIV-negative because they have not proposed condom use or even because of their appearance or another characteristic, while others ask their partner's HIV status and then behave accordingly. Similarly, an HIV-positive individual who serosorts would restrict his condomless sexual encounters only to others who share his positive serostatus-a conclusion that can be reached in similar ways to HIV-negative individuals. Crucially, individuals who serosort often forego condoms.

Yet, there are significant problems with this prevention option, which is all too frequently used as a replacement for consistent condom use. The first is its lack of efficacy. The national recommendation in the UK is for high-risk gay men (i.e. those who engage in condomless anal sex) to be screened every three months for bacterial and viral STIs (chlamydia, gonorrhoea, HIV, syphilis and hepatitis B and C-depending on sexual behaviour). It is known that only one third of gay men in England frequently use sexual health services (Mercer et al., 2016) . Thus, in a serosorting context, an individual may believe himself to be HIV-negative on the basis of their last HIV test (however long ago that may have been) but actually have acquired the infection since his last test and therefore be living with undiagnosed HIV.

Indeed, approximately 20% of people who acquire HIV will not exhibit symptoms during HIV seroconversion, and those who experience mild symptoms may misattribute them to a cold, influenza or even COVID-19. These issues are inextricably entwined with questions of risk perception, personality and healthcare engagement. However, they have decisive implications for HIV transmissions-in the early stages of HIV seroconversion, the individual's viral load is extremely high which translates into an extremely high risk of onward HIV transmission.

A second challenge concerns the stigma that is implicit in serosorting. The selection of sexual partners on the basis of their HIV status will include some and exclude others. This can fuel stigma against gay men living with HIV who may actually pose a lower risk than those claiming to be HIV-negative, given that those who are living with HIV but on effective ART with an undetectable viral load are not infectious (U=U [undetectable=untransmittable] ). Yet, this scientific fact may be discarded by some gay men who serosort. Furthermore, the rejection of gay men living with HIV due to their HIV status may lead some to conceal it from others as a self-protection strategy, potentially leading to onward transmission to others. Indeed, a recurrent theme in this book is that HIV stigma is a key barrier to effective prevention. However, it must be noted that, despite the enormous advantage of U=U, condom use does appear to be waning among HIV-positive gay men with an undetectable viral load because they are increasingly aware that they are not infectious. This of course poses no risk to the HIV prevention agenda but is clearly contributing to the higher incidence of STIs observable in gay men.

Condom use among gay men continues to change as other methods of HIV prevention are emerging. In their study of 4388 gay men and transgender women, Traeger et al. (2018) found that PrEP use was significantly and positively associated with increases in rectal gonorrhoea, which is an indicator of condomless receptive anal intercourse. This suggests that PrEP users are less likely to use condoms consistently, which puts them at higher risk of STIs. Yet, it is perhaps due to social stigma towards gay men who do not use condoms that they are accused of recklessness when they do not use them. To contextualise, studies have found that rates of consistent condom use in heterosexual men in the UK are also approximately 40%, although they tend not to face the level of stigma that gay men report (Clifton et al., 2018) . A key point is that gay men who, for whatever reason, do not consistently use condoms must be empowered to do so but also signposted to other effective prevention options, such as PrEP. Ultimately, the prime objective is to eradicate new HIV infections in those gay men at risk.

HIV testing is key to prevention for at least two reasons: first, it enables people to know their HIV status and to modify their sexual behaviour accordingly, and, second, it provides an opportunity to acquire information about how one can limit one's risk of infection and the risk to others. The majority of sexual health clinics in the UK provide an 'opt-out' HIV testing service for patients who wish to be screened for STIs. In most clinics, a fourth-generation combined antigen/antibody HIV test is offered routinely with results usually available within 48-72 hours. Increasingly, rapid finger-prick HIV tests are being offered in community settings, such as LGBT charities, sexual health charities, LGBT nightclub venues and gay saunas. Many gay men prefer to test in these contexts (Thornton, Delpech, Kall, & Nardone, 2012 ). In addition, HIV selftesting has been legal in the UK since 2014. Self-testing kits can be purchased online and, at the time of writing, cost 29.95 UK pounds (approximately 40 US dollars). The individual personally conducts the test and receives the results within 15 minutes. No interaction with a healthcare professional is usually required. Given there are now a range of contexts in which one can test for HIV, it is crucial to understand attitudes towards them among gay men.

In previous research (e.g. Evangeli, Pady, & Wroe, 2016) , several social and psychological barriers to regular HIV testing have been identified.

• Fear of mortality and illness as a result of HIV can lead some individuals to prefer not to know their HIV status (Lorenc et al., 2011) . • Some gay men do not view themselves as being at risk of HIV due, for instance, to low levels of awareness of HIV risk factors or because they do not self-identify as gay (Bond et al., 2015) . People who perceive themselves to be at low risk of HIV are in turn less likely to test (Marcus, Gassowski, & Drewes, 2016) . • Endorsement of HIV-related stigma is negatively associated with HIV testing in gay men (Li, Gilmour, Zhang, Koyanagi, & Shibuya, 2012) . Individuals may refrain from testing for HIV in order to avoid selfassociation with this stigmatised condition (Young, Nussbaum, & Monin, 2007) . • In the case of ethnic minority gay men, prejudice, such as homophobia and racism, is associated with decreased willingness to test for HIV (Bond et al., 2015) .

Some of these barriers may be accentuated in some testing venues and attenuated in others. For instance, some gay men anticipate homophobia from healthcare professionals and, thus, avoid testing for HIV in sexual health clinics, while others may avoid testing in LGBT community settings due to fears of involuntary disclosure of their HIV status (Stutterheim et al., 2014) . HIV testing in sexual health clinics can provide the opportunity for education and facilitation of behaviour change to reduce one's risk of acquiring HIV or of transmitting it to others. However, on the whole, gay men in the UK express satisfaction with sexual health services, and many regularly test for HIV in this context (Kurka, Soni, & Richardson, 2015) . Gay men may express ambivalence about testing in sexual health clinics due to concerns about stigma, loss of confidentiality and trustworthiness of healthcare professionals (St. Lawrence et al., 2015) . Moreover, one's experience and satisfaction with sexual health services is likely to underpin future willingness to test in this context. Perceived discrimination and lack of empathy in healthcare settings can decrease willingness to test (Heijnders & Van Der Meij, 2006) . Self-stigma can derive from perceived stigma in healthcare settings and may adversely affect engagement with health services, as well as HIV testing. MacKellar et al.'s (2005) study of undiagnosed HIV and sexual risk behaviours among young gay men concludes with the recommendation that HIV testing should be expanded to gay bars, clubs and other social venues. The authors argue that the inclusion of testing in gay bathhouses and sex-on-premises venues would be effective in reaching gay men who are unaware of their positive serostatus. Rapid HIV testing in sexual health clinics and in bathhouse-based interventions appears to have high acceptability among gay men (Kendrick et al., 2005) . Prost et al. (2007) conducted a study of gay men's perceptions of rapid HIV testing in social venues as a means of exploring the provision of testing in non-clinical settings. They found that men might refrain from testing in these settings due to (1) concerns about lack of privacy, (2) the perception that social venues are inappropriate spaces for learning one's HIV status, (3) concerns about a possible lack of post-test support and about the types of behaviour in which one might engage and (4) fears that the provision of HIV testing could have an adverse effect on the venues in which it is offered.

Furthermore, internalised homophobia can result in avoidance of HIV testing in LGBT community settings. HIV self-testing can obviate many of the obstacles that individuals perceive in relation to HIV testing in sexual health and community settings, and acceptability of HIV self-testing appears to be high among gay men (Figueroa, Johnson, Verster, & Baggaley, 2015) . Convenience and confidentiality can facilitate HIV selftesting, while concerns around domestic confidentiality may impede it (Witzel, Rodger, Burns, Rhodes, & Weatherburn, 2016) . Moreover, some people have experienced difficulties in utilising self-testing kits (Johnson et al., 2014) It is clear that HIV testing is a key component of effective HIV prevention, but that there are several barriers to testing in specific contexts for gay men at risk of HIV. These barriers must be investigated, understood and removed in order to promote this vital prevention tool and to reap its full benefits. However, it is not only HIV testing, which is important-STI testing also plays a fundamental role.

The synergy between HIV and STIs has been known for several decades but is only partially understood (Røttingen, Cameron, & Garnett, 2001) . The role of rectal gonorrhoea as an indicator of condomless sex and therefore increased HIV risk has already been outlined. The most important group of STIs, that affect HIV transmission and acquisition, are those that cause genital ulceration, namely, syphilis and herpes simplex virus (HSV) in developed countries. Disruption of the mucosa, usually the first line of defence against pathogens, leads to an increase in the risk of HIV. It has been suggested that having symptomatic HSV, for example, increases one's risk of HIV acquisition three-to fivefold (Wald & Link, 2002) , although it is difficult to demonstrate unequivocally the causal effect of HSV (Freeman et al., 2006) . Accordingly, use of acyclovir to treat HSV and, as a consequence, to reduce HIV incidence has been considered. A large randomised control trial with over 3000 gay men (Connie Celum et al., 2008 ) demonstrated a reduction in genital ulcer disease and active herpes lesions for those taking acyclovir but no concurrent reduction in HIV incidence.

In addition to examining the risk of HIV acquisition, the impact of herpes on the transmission of HIV has been investigated. It has been shown in several studies that, in people who are living with HIV and have genital HSV-2 infections, the HIV viral load in genital secretions is two to four times higher than those with no HSV-2 infection (Galvin & Cohen, 2004) . This increased shedding of virus stimulates the cellmediated immune system, and attracts and activates CD4 cells, which in turn become an easy target for HIV entering the bloodstream (Biancotto et al., 2008; Root-Bernstein & Hobbs, 1993) . This 'double whammy' of viral induction and propagation means that the genital tract will take up HIV more readily in those with HSV than those without.

A large trial examined whether treating HSV-2 with acyclovir in patients living with HIV and assessed HIV rates in their HIV-negative partners (Celum et al., 2010) . The results of data from nearly 3500 couples showed that, despite reducing the prevalence of genital ulcers and HSV-2 outbreaks, it had no effect on reducing HIV transmission to one's partner. Interestingly, acyclovir did lead to a reduction in the level of HIV in the plasma (and most likely the genital tract) by an appreciable amount, but again was not found to be effective in reducing HIV transmission. The disappointing results of these clinical trials show the complexity of HIV transmission risk and, similarly, the complexities associated with developing effective prevention.

For the treatment of STIs overall, it seems sensible that reducing the frequency and latency time (by improved testing and detection) would lead to reduced incidence of HIV. To date, there have been four clinical trials looking at this, mainly based in Africa (Gregson et al., 2007; Grosskurth et al., 1995; Kamali et al., 2003; Wawer et al., 1999) . Only the trial based in Tanzania demonstrated lowered HIV rates, with the other three showing lower levels of STIs as expected, but no discernible effect on HIV transmission. The rates of HIV were much lower in the successful study when compared to the others possibly indicating that the HIV epidemic was more established with fewer episodes of risky sexual behaviour and with fewer subsequent new HIV diagnoses.

Although controlling STIs does not appear to reduce HIV rates, a focus on STI prevention does stimulate patient engagement with sexual health services. It is very clear that engagement with sexual health services not only improves sexual efficacy and confidence but it also provides a perfect opportunity to educate and improve knowledge of how to have a safe healthy sex life and relationship. Improving understanding of one's sexual health alone is a good predictor of HIV prevention and allows clinicians to identify those who are having risky sex and to intervene preemptively with an acceptable and personalised behavioural and/or biomedical HIV prevention intervention.

Post-exposure prophylaxis (PEP) is a biomedical approach to HIV prevention which is administered to patients after possible HIV exposure. In the UK, the treatment consists of a three-drug regimen-two non-nucleoside reverse transcriptase inhibitors (emtricitabine and tenofovir) and an integrase inhibitor (raltegravir). If initiated within 72 hours of possible exposure to HIV and taken for a period of 28 days, PEP is thought to be protective against permanent HIV infection (Cresswell et al., 2016) . Although PEP was approved in 1988, it has remained a controversial prevention method for cases of sexual exposure to HIV. While supporters view it as an effective and, thus, important prevention tool, opponents fear that it can cause serious side effects, increase sexual risk-taking and undermine public health (Jaspal & Nerlich, 2016; Richens, 2005) .

PEP has been in use since 1988, when the drug zidovudine was first used in healthcare workers potentially exposed to HIV in the workplace. There have been no randomised control trials in humans to determine the effectiveness of PEP due to the ethical problems of withholding a potentially effective prevention method from the control group. However, PEP is thought to be an effective prevention approach. An early retrospective study among healthcare workers who might have been exposed to HIV in the workplace estimated that PEP reduced the risk of infection by 81% (with a confidence interval of 48-94%) (Cardo et al., 1997) . Furthermore, there have been several animal studies which show high efficacy-one animal trial revealed that HIV infection was prevented in all of the macaque monkeys who had been intravenously inoculated with HIV, when PEP was administered within 24 hours of exposure and for 28 days continuously (Tsai et al., 1995) .

PEP is not guaranteed to inhibit HIV infection. Its effectiveness depends in part on the following factors:

• The length of time between the exposure and start of treatment: PEP is most likely to be successful if it is initiated as soon as possible after initial exposure, preferably within four hours. It is not usually prescribed after 72 hours since it is no longer thought to be effective beyond this point (Roland et al., 2005) .

• Adherence to the medication: The available evidence suggests that PEP must be taken consistently for a period of 28 days after initial exposure. In a systematic review of 97 studies , it was shown that only 56.6% of individuals eligible for PEP (reporting a range of types of exposure) actually completed the full course. This may be attributed partly to side effects, a subjective reappraisal of HIV risk and stigma. • Drug resistance: An individual may be exposed to a strain of HIV which is resistant to the drugs used as part of PEP. Though rare, this renders PEP ineffective (Beltrami, Luo, de la Torre, & Cardo, 2002) .

In view of the apparent effectiveness of PEP in preventing infection in healthcare workers and its proven effectiveness in animal trials, PEP was considered as a possible prevention tool in the context of sexual exposure to HIV in the early 1990s. In 2006, the British Association of Sexual Health and HIV and the British HIV Association published guidelines on the appropriate use of PEP for non-occupational exposure. The guidelines outline the circumstances in which PEP is recommended, considered and not recommended (see Table 4 .1).

In 2006, the then Chief Medical Officer for England, Sir Liam Donaldson requested that local NHS agencies make PEP available to those thought to have been exposed to HIV through sexual contact. Accordingly, patients were able to access PEP at NHS sexual health clinics and at Accident and Emergency Departments following suspected HIV exposure, subject to medical approval. It has been shown that not all health practitioners are fully aware of PEP (Benn et al., 2011) which suggests that not all patients potentially exposed to HIV will be offered it (Spence, 2003) .

As outlined in Chap. 3, some gay men have a sense of invincibility in relation to HIV, which some critics believe could be accentuated in the context of PEP, and increase sexual risk-taking and the incidence of HIV and other STIs (Richens, 2005) . Indeed, there is an emerging social representation in the era of ART that HIV is no longer a serious illness, which may increase condom fatigue among gay men (Shernoff, 2006) . It must be noted, however, that empirical studies have generally found little Cresswell et al. (2016) evidence that PEP increases sexual risk-taking and most users of PEP do not request it repeatedly (Donnell et al., 2010) . It is important to understand the acceptability of PEP in order to determine its effectiveness in preventing HIV. In their Australian study of PEP users, Körner et al. (2003) found that PEP had an empowering effect for users and enabled them to regain feelings of control over their sexual health. Furthermore, in interviews with 15 gay men who were using PEP following sexual exposure, Sayer et al. (2009) found that, while participants had high awareness of PEP, they did not really understand it, but stated that the experience of taking PEP had led them to engage in less anal sex with casual partners (see also Körner et al. 2003) . In short, although there is some awareness of PEP among gay men, due in part to its visibility in gay social contexts as a relevant health-related issue (de Silva, Miller, & Walsh, 2006) , understanding of PEP (and particularly of the circumstances in which it is most effective) remains low.

Jaspal and Nerlich (2016) examined representations of PEP in the British print media, a key source of information regarding health, science and medicine, between 1997 and 2015. They identified three key social representations of PEP. In some articles, PEP was represented as a straightforward 'morning-after pill' which can prevent HIV, and in others, it was represented as posing risks to individual and public health and yielding uncertain outcomes. A third representation positioned healthcare workers as deserving recipients of PEP and gay men as being less ideal candidates for the prevention tool. The authors argued that media representations of this kind-devoid of technical information about PEP and its mechanisms-might lead to polarised perceptions of PEP, stigma of users and decreased PEP acceptability among both those who prescribe it and those who can benefit from it.

Pre-exposure prophylaxis (PrEP) is a biomedical HIV prevention tool that has shaped the HIV prevention landscape over the last decade by helping countless patients reduce their risk of HIV while enjoying a fulfilling sex life, with or without condoms. Its role in reducing HIV is unequivocal and, accordingly, it has been referred to as the 'game changer' of HIV prevention (Jaspal & Nerlich, 2016) . Though clinically effective, it has not been fully available, or acceptable, to all patients at risk of HIV.

As outlined earlier, it can take up to 17 years for a drug to be made available to patients after initial drug discovery. This is also true of PrEP. In November 1995, a team of US researchers explored the use of tenofovir as a treatment for HIV and as a possible prevention tool (Tsai et al., 1995) . Their study, published in Science, described the effect of tenofovir versus placebo on HIV infection in macaque monkeys who had been inoculated with HIV. For those treated with tenofovir either before or after exposure for four weeks, HIV infection was prevented in 100% of the macaques. This seminal research paved the way for both PEP and PrEP.

The advent of PrEP has been a game changer for many gay men. A significant minority have found it difficult to use condoms, be it due to reduced pleasure, personal choice or erection difficulties. Also, many gay men have been in a situation where condoms fail (i.e. break or slip off during sex) leading to stressful episodes of worry and attending clinic for PEP. This 'HIV anxiety' syndrome is a well-trodden path for many. PrEP not only protects against HIV but also reduces this level of anxiety leading to more enjoyable sex

The first real-world study of PrEP in gay men materialised several years later. The iPrEx (preexposure prophylaxis initiative) randomised control trial in 2010 recruited almost 2500 gay men and transgender women at high risk of HIV infection (Grant et al., 2010) . They received either placebo or Truvada (containing tenofovir and emtricitabine), which they were instructed to take daily. The trial demonstrated, for the first time, that daily Truvada reduced HIV incidence in the experimental group by 44%, an impressive reduction with significant public health ramifications. A strong indicator of effectiveness was the amount of drug in the blood of the participants-with high levels showing a strong correlation between drug adherence and protection against HIV. The iPrEx trial was a significant step forward for gay men at risk of HIV infection since it added another effective prevention method to the HIV prevention toolbox. HIV incidence in gay men had been on the rise, and it had become clear that the social norm of condom use was beginning to wane (Shernoff, 2006) .

Following the promising results of the iPrEx trial, two additional clinical trials were conducted in the UK and in France-the PROUD (McCormack et al., 2016) and iPERGAY (Molina et al., 2015) studies, respectively. These trials set out to examine not only the effectiveness of PrEP but also the degree of risk compensation among PrEP users, that is, whether rates of condom use would decrease, in turn leading to increased STI rates. Moreover, the trials aimed to address the additional questions that had been raised in the iPrEx study, such as whether gay men would adhere to daily PrEP and what the alternatives to daily PrEP might be; whether gay men would acquire a false sense of protection against HIV despite poor adherence, leading to HIV infection; and how sexual health clinics might incorporate and manage PrEP within their existing services.

As in the iPrEx study, PROUD trial participants were randomly allocated to taking immediate PrEP or deferring PrEP for the first year and then taking Truvada daily. The results of the study were very encouraging, and when it became evident that PrEP worked, the trial was stopped early and all participants were offered PrEP immediately. The trial showed that PrEP reduced HIV incidence by 86% although it must be noted that some participants in the experimental group did not adhere to the drug, which suggests that the efficacy rate may have been higher if adherence had been better.

Meanwhile, the French research group released data for iPERGAY (Molina et al., 2015) , which had tested the efficacy of the same Truvada formulation as PrEP, but with a different dosage. Participants in the trial were instructed to take PrEP before and after sex (two tablets 2-24 hours before, followed by one tablet 24 hours later and a fourth tablet 48 hours later). The iPERGAY trial demonstrated an 86% reduction in HIV in participants, showing that intermittent dosage worked as effectively as daily PrEP.

Understandably there were concerns about the possible side effects of PrEP. Truvada had been used to treat HIV since the FDA in the US approved its use in 2004. Therefore, a great deal was known about its toxicity profile before it was licensed for use as PrEP. The main short-term side effects were found to include nausea, diarrhoea and headaches, which usually settle in the first few weeks. However, in practice, these are relatively uncommon. Long-term side effects include renal complications and a modest reduction in bone density. One of the main clinical concerns in relation to Truvada was renal injury observed in HIV patients when administered with other HIV drugs. However, for those taking Truvada alone, it was thought this renal damage may also be an issue. A large meta-analysis (Pilkington, Hill, Hughes, Nwokolo, & Pozniak, 2018) of over 15,000 people did not show increased rates of serious kidney damage for those taking PrEP, and thus yearly kidney monitoring is deemed to be sufficient.

The iPREX-OLE (open label extension) showed between a 0.5% and 1% loss of bone density in the hip and spine, respectively. In HIV negative patients, who are otherwise fit and well, this slight decrease in bone density is unlikely to lead to a higher risk of fracture. It is important to counsel patients about this risk, but with reassurances that it should not prevent them from taking PrEP if the benefits outweigh the possible risks.

The initial exorbitant cost of branded Truvada led many to acquire it from non-NHS settings (i.e. ordered online from other countries). Clinicians in the UK were concerned about advocating the use of nonbranded Truvada from pharmaceutical companies based mainly in India and Canada. In particular, clinicians expressed concern about nonapproval of the drugs by the European Medicines Agency and the possibility that the formulations did not contain the correct drugs or dosage. However, a study with those taking these non-branded drugs found that the drugs contained the same active ingredients as branded Truvada, eliminating this concern (Wang et al., 2019) .

In view of the convincing evidence regarding the impact of PrEP on HIV incidence, physicians and many in the gay community assumed that PrEP would be commissioned on the NHS. As pressure mounted on the government to provide PrEP to all, NHS England declined to fund the drug, stating that this was the responsibility of local authorities who currently fund sexual and reproductive healthcare in line with the Health and Social Care Act in 2012. The argument of NHS England was that it was responsible solely for HIV treatment (i.e. the treatment of those living with HIV) and that local authorities should fund HIV prevention from within their own budgets. In the era of austerity in the UK since the financial crash of 2009, budgets for public health were radically affected, with reductions of up to 40% in some boroughs. It was therefore unrealistic to expect local authorities to fund PrEP in their respective jurisdictions.

There was a significant community response with individuals and thirdsector agencies taking on the responsibility of raising awareness of PrEP and how to access it. In the absence of a national commissioning strategy, activists and clinicians took the lead in ensuring this new prevention tool could become available to the many who needed it. Community activists set up a website 4 with information about PrEP and the option to purchase a generic version of PrEP at a fraction of the cost compared to Truvada. At the time, Gilead Sciences who had developed Truvada held the cost of a 30-day supply of PrEP at approximately £400, which was of course unaffordable for most people at risk of HIV. Given the complexities of drug patents, the US and Europe were unable to access generic PrEP (i.e. the same drugs as Truvada, but manufactured by other pharmaceutical companies at a lower cost). However, in the UK, Greg Owen (an activist living with HIV) and Dr Mags Portman (a consultant physician in HIV medicine) facilitated access to generic PrEP to many of those at risk (especially those in the gay community) and helped prevent thousands of new HIV infections.

The National AIDS Trust led the campaign to have the decision of NHS England not to fund PrEP overturned by the UK High Court in August 2016. After the successful High Court ruling, NHS England released a press statement, which began 'PrEP is a measure to prevent HIV transmission, particularly for men who have high-risk condomless sex with multiple male partners'. 5 The statement served to emphasise the benefits of PrEP to one group only-gay men-when it has been shown to be equally as effective in women, and to associate the prevention tool with 'high risk condomless sex with multiple male partners'. It is easy to see how this might have paved the way for polarised thinking and stigmatising perceptions not only of gay men but also PrEP.

However, in 2017, NHS England finally capitulated and instructed Public Health England to investigate the possibility of commissioning PrEP in England. This led to a second clinical trial-the IMPACT study-which, in many respects, replicated the work of the PROUD study eight years earlier. At the time of writing, the trial was still recruiting participants. However, in March 2020, Matt Hancock, the Secretary of State for Health and Social Care, announced that PrEP would be made available on the NHS free of charge to those at risk of HIV. Although PrEP was due to be made available in April of that year, the outbreak of COVID-19 (and the subsequent measures taken to curb its spread) has delayed this.

The media make important contributions to perceptions of PrEP in the general population. Jaspal and Nerlich (2017) found that media reporting of PrEP in the UK was polarised in that it represented PrEP either as a 'magic bullet' or as posing severe risks to individual and public health. Much of the reporting in the latter theme was characterised by social stigma-of HIV, of gay men and of PrEP itself.

In addition, as an 'expert community', healthcare professionals are of course key to the development of societal perceptions of PrEP. They have the ability to influence both public policy and patient engagement. In a survey of 328 healthcare professionals in the UK, Desai et al. (2016) found that just 54% of those surveyed endorsed PrEP for patients outside of the clinical trial and raised concerns about the current evidence base, patient adherence to PrEP and the potential for increased sexual risktaking in patients. It is important to examine how healthcare professionals think and talk about PrEP-especially with patients-because their approach to PrEP is likely to influence that of patients. Indeed, in previous research, it has been noted that stigmatisation from both healthcare professionals and other gay men was a common experience for participants in a qualitative study of PrEP users (Schwartz & Grimm, 2019) . It is easy to see how stigma can challenge self-esteem among patients and, thus, inhibit access to PrEP and also interfere with adherence to the drug, which itself can reduce its effectiveness (Vaccher, Kaldor, Callander, Zablotska, & Haire, 2018) . It has also been found that perceived stigma from healthcare professionals can decrease engagement with sexual healthcare (Williamson, Papaloukas, Jaspal, & Lond, 2019) .

Although PrEP is clinically effective, its effectiveness depends on its acceptability among potential users. Given that gay men are one of the groups in society that are disproportionately affected by HIV, it is necessary to assess perceptions and acceptability of PrEP in this group. There have been several studies of PrEP awareness, understanding and acceptability among gay men (Williamson et al., 2019; Jaspal, Lopes, Bayley, & Papaloukas, 2019) . A survey study of 386 HIV-negative gay men revealed that just a third of respondents had heard of PrEP but that over half would be willing to utilise it if it were available (Frankis, Young, Flowers, & McDaid, 2016) . Those who tested for HIV every six months were more likely to be aware of PrEP. In their survey study of gay men in Leicester, Jaspal et al. (2019) found socio-economic inequalities in HIV knowledge and HIV testing, both of which are important predictors of PrEP acceptability. More specifically, it was found that gay men who have high levels of HIV knowledge and perceived HIV risk and who test for HIV regularly are most likely to perceive PrEP to be of personal benefit. Their findings indicated that one must first view oneself as being at risk of HIV (possibly through consultation with a healthcare professional) in order to accept PrEP as a viable HIV prevention method for oneself. In a US study, Raifman et al. (2019) examined awareness of PrEP among gay men presenting at a sexual health clinic from 2013 to 2016 and found that awareness increased over time, although Hispanic and Black gay men manifested consistently lower PrEP awareness than White gay men. Furthermore, Elopre et al. (2018) studied perceptions of PrEP among Black gay men and found that interviewees perceived a multi-faceted stigma in relation to their Black, gay and Southern identities, a lack of discussion regarding HIV prevention in the Black community and low HIV risk perception (Elopre et al., 2018) .

This research suggests that societal perceptions of PrEP are developing and being disseminated to people at risk of HIV, such as gay men, but that there are some subgroups of gay men that have less access to this knowledge. Furthermore, it has been shown that gay men who participate in the gay community are more likely to be aware of PrEP than those who do not (Zarwell, Ransome, Barak, Gruber, & Robinson, 2019) . Several empirical studies (e.g. Jaspal, 2019; Jaspal & Cinnirella, 2010) have revealed that ethnic minority gay men are less likely to be open about their sexual identity and less involved in the gay community. This can mean that they are less aware of issues that affect the gay community, such as HIV and PrEP. They may not be exposed to discussions about PrEP that ordinarily take place in gay social contexts. Furthermore, in order to protect self-esteem, individuals may avoid exposure to stigma, thereby reducing access to PrEP.

In addition to awareness, complex psychosocial factors like risk appraisal and perceived stigma also shape PrEP acceptability in gay men. Frankis, Young, Flowers, and McDaid (2014) found that few of the gay men they interviewed regarded themselves as candidates for PrEP because of low perceived risk of HIV and existing HIV prevention strategies that they were utilising. In view of the low uptake of PrEP in groups at high risk of HIV, Dubov, Galbo, Altice, and Fraenkel (2018) conducted semistructured interviews with 43 HIV-negative gay men to explore their perceptions and experiences of stigma in relation to PrEP use. They found that interviewees experienced stigma from potential and actual sexual partners and reported being stereotyped as 'high risk'. Participants associated PrEP stigma with HIV stigma. In a qualitative interview study of Latino gay male PrEP users in Los Angeles, Brooks, Nieto, Landrian, and Donohoe (2019) found that perceptions that PrEP users engage in sexual risk behaviours and that they are in fact HIV-positive underpinned the stigma that participants faced. Moreover, interviewees described the risk of difficulties in relationships as a result of their PrEP use. Given the higher levels of internalised homophobia and motivation to conceal their sexual identity, ethnic minority gay men at risk of HIV may express concerns about involuntary disclosure of their sexual orientation and about potential exposure to HIV stigma as a result of PrEP use. Avoidance may constitute a strategy for coping with threats to self-esteem associated with potential or actual stigma.

In a qualitative interview study, Jaspal and Daramilas (2016) explored perceptions and understandings of PrEP among 20 HIV-negative and HIV-positive gay men, focusing on their beliefs about the potential impact of PrEP on their own lives and behaviours. They found three themes: uncertainty and fear, managing relationships with others and stigma and categorisation. HIV-negative participants appeared to manifest uncertainty and fear in relation to PrEP as they believed that it would not be completely effective and that it would leave them feeling uncertain due to the 'invisibility' of PrEP once it is taken (versus a condom which can be examined physically to ensure that it has remained intact during sex). Conversely, HIV-positive gay men were generally of the view that PrEP would reduce uncertainty and fear (primarily of onward HIV transmission to HIV-negative partners). It is possible that this might provide a sense of self-efficacy in that individuals feel more empowered to prevent onward transmission than they previously did with condoms as their sole prevention approach. There was a stark difference in how HIV-negative and HIV-positive men perceived the potential impact of PrEP on their relationships with others-while HIV-negative gay men felt that their use of PrEP could induce social stigma, HIV-positive men foresaw an improvement in relations with serodiscordant partners who they believed might feel less anxious about sex given the advent of PrEP.

Although both cohorts acknowledged the possible benefits of PrEP, they nonetheless manifested stigma in relation to the prevention tool, which led some HIV-negative gay men to reject PrEP for personal use. It is clear that social stigma underpins attitudes towards PrEP both at social (i.e. in the media) and individual levels. The prevalence of social stigma appears to have infiltrated thinking at an individual level, which has led individuals who may benefit from PrEP to reject it as an HIV prevention tool that people 'at high risk' might utilise. It is important that potential beneficiaries of PrEP are able to understand the benefits of this approach in preventing HIV and to access it. It is likely that social and political factors may inhibit this.

One of the greatest advancements in the fight against HIV has undoubtedly been TasP, which refers to the treatment of HIV (using ART) in those who have the infection. Essentially, effective ART reduces the

The release of the HPTN-052 and PARTNERS studies showed unequivocally that those taking effective ART cannot pass HIV on to their partners. Clinicians rarely deal in absolutes-however, the data surrounding U=U are clear and unambiguous. This certainty allows clinicians to relay this important information to their patients. In practice, this message is one of the most powerful for a number of reasons. Those living with HIV have often lived with the anxiety of possibly passing HIV on to their partners and loved ones-an anxiety that can cause shame and/or damage to relationships. The U=U message has important ramifications not only for reducing HIV transmissions but also for anxious patients. The reaction to this message in clinical practice is often one of relief and should be part of every HIV consultation-and reiterated as some patients take time to adjust to the relief of this news. The ability to have sex with a partner without anxiety is a significant step towards enhancing the quality of life of those living with HIV.

individual's viral load to undetectable levels, which in turn reduces their risk of HIV transmission to zero. The most successful early case of TasP involved the use of AZT in pregnancy which was shown to reduce HIV transmission from HIV-positive mothers to their infants by up to two thirds (Connor et al., 1994) . In 2000, a large study of 415 serodiscordant (i.e. one partner with HIV and one without it) heterosexual couples in Rakai, Uganda, showed that, over a period of 30 months, just over 20% of the HIV-negative individuals acquired HIV with a strong correlation between viral load and risk of HIV transmission (Quinn et al., 2000) . Furthermore, there were no HIV transmissions when the HIV-positive individual's viral load was less than 1500 copies per millilitre.

The next seminal moment came in 2011 when the HIV Prevention Trial Network, a global coalition of clinicians and researchers published the results of the HPTN 052 study (Cohen et al., 2011) . The study included 1763 serodiscordant couples, of which 97% were heterosexual, in South America, Africa and Asia. The HIV-positive partner in each couple was assigned to either 'delayed' treatment (i.e. waiting until the CD4 count had dropped to less than 200 cells/mm 3 ) or 'immediate' treatment (i.e. start treatment when the CD4 was between 350 and 550 cells/mm 3 ). Out of the 28 transmissions, 27 were from those who had delayed treatment with only one from the group on treatment. In other words, those on treatment were 96% less likely to transmit HIV than those who had deferred treatment. Such compelling results are rarely seen in such large clinical trials, given that human behaviour and chance often obfuscate the true effects of interventions. The results exceeded expectations and were hailed as a landmark in the history of HIV prevention.

As this was a study of heterosexual couples, the findings could not be easily generalised to gay men. Relevant data arrived five years later in the form of the PARTNER study which included a significant subsample of men who were in gay relationships. The trial results revealed zero linked transmissions of HIV if one partner was on effective HIV treatment and undetectable. This added to the evidence base that HIV transmission was impossible whilst taking effective HIV treatment-this time in gay couples. This evidence was reinforced with an extension of the original trial for only gay couples-in over 76,000 acts of condomless anal sex, there were zero linked HIV transmissions (Rodger et al., 2019) . Since one of the main psychological challenges faced by people living with HIV concerns the management of risk of onward transmission, this finding was life-changing for many. Clinicians across the globe could now say with certainty that there was no risk of HIV transmission for gay men living with HIV who are taking effective treatment.

These data underpinned the simple and powerful public health message of U=U. This message has since been the focus of a global effort to reduce anxiety among and reduce stigma towards those who are living with HIV. Community groups, activists and clinicians have been vociferous in their support for this message. U=U has been the most powerful (and emotional) message relayed to patients who often report feeling relieved and empowered as a result.

In addition to the major components of combination HIV prevention, namely, condom use, HIV testing, PrEP and TasP, other prevention options that might complement these approaches are being explored. Interesting possible approaches include the use of microbicides and male circumcision. Much of the research into these approaches has focused on heterosexual populations but may also be transferable to gay men. Some interest has been shown in the possibility of using topical preparations of anti-HIV drugs, mainly tenofovir disoproxil, to reduce the risk of HIV. The CAPRISA 004 study (Abdool Karim et al., 2010) evaluated the effectiveness of a vaginal gel containing 1% tenofovir which led to a 39% reduction in HIV infections when compared to placebo. However, adherence to the gel was poor. Another trial has focused on nonoxynol-9, a commonly used spermicide (which appears to be moderately protective against HIV and most STIs), in a vaginal gel (Van Damme et al., 2002) . However, its use led to higher rates of genital ulceration and may in fact have increased the risk of HIV acquisition. It is possible that use of gels in the rectum also cause mucosal damage, thereby undermining their effectiveness as HIV prevention tools. Although some gay men have expressed interest in rectal gels, many prefer to use oral Truvada (Carballo-Diéguez et al., 2017) . Yet, rectal gels may provide another tool for prevention and may suit gay men who find oral PrEP unacceptable. However, no commercial gel is, as yet, available.

The impact of circumcision on HIV risk in gay men has also been considered (Yuan et al., 2019) . The procedure entails the surgical removal of the foreskin-often for cultural, religious and medical reasons. During the early days of the epidemic, it was noted that men who were uncircumcised (i.e. their foreskin remained intact) appeared to be at higher risk of acquiring HIV than those who were circumcised. An African study revealed an eightfold increase in HIV risk in uncircumcised men (Cameron et al., 1989) which subsequently led to research into whether male circumcision might constitute a feasible and cost-effective HIV prevention method, especially in developing countries. There have since been several large trials in Africa (Auvert et al., 2005; Bailey et al., 2007; Gray et al., 2007) which have generally shown a reduction of almost 60% in circumcised men compared to uncircumcised men. Evidently, circumcision is clinically effective but it has varying degrees of cultural and individual acceptability.

It is noteworthy that the aforementioned trials were all designed for heterosexual men who perform the insertive role in sex. However, sexual behaviour among gay men tends to vary between insertive and receptive sexual practices. A large meta-analysis (Yuan et al., 2019) examined the effectiveness of circumcision in gay men after two previous meta-analyses had shown no effect in this population (Millett, Flores, Marks, Reed, & Herbst, 2008; Wiysonge et al., 2011) . The meta-analyses included data from over 100,000 gay men from low-, middle-and high-income countries and demonstrated 23% protection overall. However, the protective effect was stronger in gay men in low-and middle-income countries, those who mainly had insertive anal sex and those under the age of 29 years. It might be advantageous to examine the acceptability of circumcision in the UK population, especially given its clear contribution to HIV prevention. However, given the effectiveness of other prevention methods, circumcision remains an under-developed method of HIV prevention in the UK.

In 1984, Margaret Heckler, the then US Secretary of State of Health, declared that 'a vaccine will be ready for testing within 2 years'. This assertion was based on successful development of vaccines for the feline leukaemia virus (FLV) and for hepatitis B in the early 1980s. However, it was not yet anticipated that developing a vaccine would be so challenging that, almost 40 years after its first clinical observations, there is still no effective vaccine for HIV.

The journey towards developing an effective preventive HIV vaccine has been long and arduous with numerous failures and a few modest successes. Viral vaccinology dictates that introduction of the whole or part of the virus in vectors (usually inert viruses which help to deliver the antigen to the body's immune system) will induce an antibody response from the patient's own immune system that then prevents future infection if challenged with the infective agent. A modern example of this is the hugely successful vaccination for Human Papillomavirus (HPV) whereby yeast cells are used to grow the external viral envelope proteins to form 'virus-like particles' which have a strong immunogenic reaction and produce high levels of protective antibodies. However, this method has thus far proven futile for HIV. Numerous vaccine trials have shown that using proteins from the surface of HIV (usually gp120 or gp160) do stimulate antibodies to HIV but that they do not appear to inactivate it. One of the biggest challenges is the heterogeneity, or variability, of HIV itself which undergoes millions of natural mutations during replication, as well as the different structures of viral subsets, or clades.

A notable trial in the search for a preventative vaccine was the much anticipated Step trial which began in 2004 (Buchbinder et al., 2008) and recruited gay and bisexual men from the Caribbean region. The trial used an adenovirus-type vaccine-shown to be the most immunogenic for anti-HIV CD4 responses-which coded for three HIV surface proteins (gag, pol and nef) in the hope the antibodies produced would protect against HIV. Sadly, the trial was terminated early after it was discovered that many of the vaccinated men who had previously been naturally exposed to adenovirus had higher rates of HIV acquisition when compared to placebo. The exact reason why those who were seropositive for adenovirus exhibited a higher rate of infection is unknown but proved a disappointment for HIV research.

There has also been another line of HIV vaccination science, focusing on combinations of immune responses, rather than on one aspect. This was tested in the Thai RV 144 study (Karasavvas et al., 2012) , one of the few success stories of HIV vaccines, albeit a modest one. This vaccine used a 'prime boost' method, where two vaccines were given in succession-the first to stimulate cell-mediated immunity (via a canarypox vector), followed by another surface protein (recombinant gp120) to stimulate the antibody response to neutralise HIV. The study recruited over 16,000 adults in Thailand but only had a modest effect in reducing HIV acquisition by 31% overall, despite showing a 60% reduction at 12 months. The level of protection provided by this vaccine means it is unlikely to be adopted in the real world given that, with such low levels of protection, vaccinated individuals may acquire a false sense of security of being 'immune' to HIV with subsequent increased sexual risk.

Given that this was one of the only effective HIV vaccines, researchers went on to develop another vaccine with a 'prime boost' model using a similar method with slight alterations to the constituents. The HVTN 702 study 6 recruited nearly 5000 adults (half receiving placebo, the other half the vaccine) in 2016 but was stopped early in February 2020 after showing no success in reducing HIV acquisition. The cost of the trial was over $100 million, showing how resource-intensive these vaccination trials can be, but they enable researchers to discard some vaccination methods in favour of potentially more fruitful methods. The search for an effective vaccine continues.

The work of HIV vaccination science is also focusing on broadly neutralising antibodies (bNAb). These antibodies were found in 20% HIVpositive patients who develop them against their own HIV. These bNAb are able to inhibit a broad range of HIV mutations and clades. The AMP trial (HVTN 704/HPTN 085) 7 has recruited over 4000 adults and delivers monoclonal antibodies in an infusion every eight weeks by disrupting a protein involved in the attachment of HIV to the CD4 cell so the HIV is not allowed to enter. At the time of writing, the results of this exciting new HIV prevention strategy were not yet available.

In this chapter, the HIV prevention landscape in the UK has been outlined. While condom use has been a long-standing norm among gay men, it is clear that this norm is now waning. This has paved the way for other innovative approaches to HIV prevention, such as PrEP and TasP. Moreover, emerging prevention approaches, such as circumcision and microbicides, have shown some promise. A recurrent theme in this chapter is that, although significant advances have been made in developing effective prevention tools, there are varying levels of patient acceptability of these distinct approaches. It is important to explore their acceptability among gay men in distinct contexts and to attempt to remove any potential barriers to accessing them. Condoms may be an effective stand-alone prevention tool for some gay men but unacceptable to others who may require PrEP. Moreover, the science underpinning TasP must be effectively communicated to gay men-both HIV-negative and HIV-positive. Public health campaigns are instrumental in educating and raising awareness of the risks of HIV, but without sustained behaviour change, the effects of these campaigns will be short-lived. The condom use message of the 1980s and 1990s had some positive effect, especially alongside the potent 'tombstone' television adverts, but HIV incidence in gay men continued to increase. To ensure that HIV is eliminated by 2030, the emphasis and funding must be weighted towards prevention, that is, driving down the number of new infections. However, it is also essential to equip gay men with knowledge concerning sex, risk and STIs so that they can take informed decisions about the most effective prevention tool for them.

Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women

Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial

Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial

Transmission of drug-resistant HIV after an occupational exposure despite postexposure prophylaxis with a combination drug regimen

UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure

HIV-1 induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo

Knowing is not enough: A qualitative report on HIV testing among heterosexual African-American men

Persistent stigmatizing and negative perceptions of pre-exposure prophylaxis (PrEP) users: Implications for PrEP adoption among Latino men who have sex with men

Efficacy assessment of a cellmediated immunity HIV-1 vaccine (the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial

Female to male transmission of human immunodeficiency virus type 1: Risk factors for seroconversion in men

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women

A case-control study of HIV seroconversion in health care workers after percutaneous exposure

Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: A randomised, double-blind, placebo-controlled trial

Partners in Prevention HSV/HIV Transmission Study Team

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2

STI risk perception in the British population and how it relates to sexual behaviour and STI healthcare use: Findings from a cross-sectional survey

Prevention of HIV-1 infection with early antiretroviral therapy

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment

UK guideline for the use of HIV post-exposure prophylaxis following sexual exposure

Lack of awareness of HIV postexposure prophylaxis among HIV-infected and uninfected men attending an inner London clinic

Healthcare providers' knowledge of, attitudes to and practice of pre-exposure prophylaxis for HIV infection

Use of non-occupational post-exposure prophylaxis does not lead to an increase in high risk sex behaviors in men who have sex with men participating in the EXPLORE trial

Stigma and shame experiences by MSM who take PrEP for HIV prevention: A qualitative study

Perceptions of HIV pre-exposure prophylaxis among young, Black Men who have sex with men

Which psychological factors are related to HIV testing? A quantitative systematic review of global studies

Attitudes and acceptability on HIV self-testing among key populations: A literature review

Adherence to HIV postexposure prophylaxis: A systematic review and meta-analysis

Understanding the acceptability of pre-exposure prophylaxis (PrEP) for HIV prevention amongst gay and bisexual men in Scotland: A mixed methods study

Who will use preexposure prophylaxis (PrEP) and why?: Understanding PrEP awareness and acceptability amongst men who have sex with men in the UK-A mixed methods study

Herpes simplex virus 2 infection increases HIV acquisition in men and women: Systematic review and meta-analysis of longitudinal studies

The role of sexually transmitted diseases in HIV transmission

Preexposure chemoprophylaxis for HIV prevention in men who have sex with men

Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial

Impact and process evaluation of integrated community and clinic-based HIV-1 control: A cluster-randomised trial in Eastern Zimbabwe

Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: Randomised controlled trial

The fight against stigma: An overview of stigma-reduction strategies and interventions

The social psychology of gay men

Coping with potentially incompatible identities: Accounts of religious, ethnic and sexual identities from British Pakistani men who identify as Muslim and gay

Perceptions of pre-exposure prophylaxis (PrEP) among HIV-negative and HIV-positive men who have sex with men

A structural equation model to predict pre-exposure prophylaxis acceptability in men who have sex with men in Leicester

A 'morning-after' pill for HIV? Social representations of post-exposure prophylaxis for HIV in the British print media

Polarised reporting about HIV prevention: Social representations of pre-exposure prophylaxis (PrEP) in the UK press. Health: An Interdisciplinary Journal for the Social Study of Health

Realizing the potential for HIV self-testing

Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: A community randomised trial

The Thai Phase III HIV Type 1 Vaccine Trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120

Outcomes of offering rapid point-of-care HIV testing in a sexually transmitted disease clinic

Taking post-exposure prophylaxis: Managing risk, reclaiming control

Sexual health services for men who have sex with men (MSM): Are they acceptable?

Temporal trends in sexual behavior among men who have sex with men in the United States

The epidemiological impact and cost-effectiveness of HIV testing, antiretroviral treatment and harm reduction programs

HIV testing among men who have sex with men (MSM): Systematic review of qualitative evidence

Unrecognized HIV infection, risk behaviors, and perceptions of risk among young men who have sex with men: Opportunities for advancing HIV prevention in the third decade of HIV/AIDS

HIV risk perception and testing behaviours among men having sex with men (MSM) reporting potential transmission risks in the previous 12 months from a large online sample of MSM living in Germany

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trial

The health and well-being of men who have sex with men (MSM) in Britain: Evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: A meta-analysis

On-demand preexposure prophylaxis in men at high risk for HIV-1 infection

Trends in condom use among MSM in the United States: The role of antiretroviral therapy and seroadaptive strategies

How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP

HIV voluntary counselling and testing for African communities in London: Learning from experiences in Kenya

Viral load and heterosexual transmission of human immunodeficiency virus Type 1

Racial and ethnic disparities in HIV pre-exposure prophylaxis awareness among men who have sex with men

Can the promotion of post-exposure prophylaxis following sexual exposure to HIV (PEPSE) cause harm?

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): Final results of a multicentre, prospective, observational study

Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIVpositive partner is using suppressive antiretroviral therapy

Seroconversion following nonoccupational postexposure prophylaxis against HIV

Does HIV 'Piggyback' on CD4-like surface proteins of sperm, viruses, and bacteria? Implications for cotransmission, cellular tropism and the induction of autoimmunity in AIDS

A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: How much really is known?

Will I? Won't I? Why do men who have sex with men present for post-exposure prophylaxis for sexual exposures?

Stigma communication surrounding PrEP: The experiences of a sample of men who have sex with men

Without condoms: Unprotected sex, gay men & barebacking

Should emergency departments offer postexposure prophylaxis for non-occupational exposure to HIV?

Attitudes toward HIV voluntary counseling and testing (VCT) among African American men who have sex with men: Concerns underlying reluctance to test

Patient and provider perspectives on HIV and HIV-related stigma in Dutch health care settings

HIV testing in community settings in resource-rich countries: A systematic review of the evidence

Effects of pre-exposure prophylaxis for the prevention of human immunodeficiency virus infection on sexual risk behavior in men who have sex with men: A systematic review and metaanalysis

-phosphonylmethoxypropyl)adenine

Global HIV & AIDS statistics-2019 fact sheet

Qualitative insights into adherence to HIV pre-exposure prophylaxis (PrEP) among Australian gay and bisexual men

Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomised controlled trial

Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: A meta-analysis

Quantification of tenofovir disoproxil fumarate and emtricitabine in generic pre-exposure prophylaxis tablets obtained from the internet

Control of sexually transmitted diseases for AIDS prevention in Uganda: A randomised community trial. Rakai Project Study Group

EMIS-2017: The European men-who-have-sex-withmen Internet survey: Key findings from 50 countries

There's this glorious pill': Gay and bisexual men in the English midlands navigate risk responsibility and pre-exposure prophylaxis

HIV self-testing among men who have sex with men (MSM) in the UK: A qualitative study of barriers and facilitators, intervention preferences and perceived impacts

Male circumcision for prevention of homosexual acquisition of HIV in men

Potential moral stigma and reactions to sexually transmitted diseases: Evidence for a disjunction fallacy

Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: A systematic review and metaanalysis of global data

PrEP indicators, social capital and social group memberships among gay, bisexual and other men who have sex with men