OBJECTIVES:The 'Undetectable equals Untransmissible' (U=U) statement is based on robust evidence. Spreading this message aims to reduce HIV stigma, increase antiretroviral therapy (ART) adherence, and improve quality of life for people with HIV (PWH). Among PWH in the UK, we assessed the proportion believing U=U and its associations with HIV-related self-stigma, mental health, and sexual satisfaction. DESIGN:Positive Voices 2022 is the largest UK national survey of PWH (April 2022-March 2023). Participants self-completed a questionnaire on socio-demographic, HIV-related, health, and lifestyle factors. METHODS:We assessed associations of demographic, socioeconomic, and HIV-related factors with belief in U=U, and associations of belief in U=U with self-stigma, depression symptoms, anxiety symptoms, and sexual satisfaction (the latter among participants who had sex in the past 3 months) using logistic regression, unadjusted and adjusted for demographic group, age, and time on ART. RESULTS:Four thousand five hundred and fifty-three people on ART were included: 2671 (59%) gay or bisexual MSM (GBMSM), 1104 (24%) women, 646 (14%) heterosexual men; 1100 (24%) participants of Black ethnicity; median (IQR) age 52 years (44-60). 4192 (92%) had heard of U=U; fewer (2906, 64%) believed it. Lack of belief in U=U was more common among older participants, heterosexuals, those with less education, those with financial hardship, and those without knowledge of their last viral load level. Lack of belief in U=U was associated with HIV-related self-stigma [adjusted odds ratio (aOR) 1.88, 95% confidence interval (CI) 1.63-2.18], depression symptoms (aOR 1.33, 95% CI 1.13-1.56) anxiety symptoms (aOR 1.48, 95% CI 1.23-1.77), and less sexual satisfaction (physical pleasure: aOR 0.62, 95% CI 0.51-0.75; emotional satisfaction: aOR 0.72, 95% CI 0.60-0.87). With the exception of depression symptoms, these associations remained after additional adjustment for financial hardship. Patterns of association were similar among GBMSM compared to all other demographic groups combined. CONCLUSION:Despite high awareness of U=U among PWH in UK, belief remains inadequate, especially in disadvantaged groups. Promoting this message could help combat HIV-related stigma and improve mental health.

Antiretroviral therapy (ART) has transformed HIV into a manageable health condition with normal life expectancy. However, people with HIV continue to have poorer mental health compared to background populations, which may be linked to stigma, lack of social support, or socioeconomic challenges. Personalised care aims to improve the outcomes of people with long-term health conditions and the National Health Service (NHS) Long Term Plan looks to implement this (including access to health coaching and social prescribing). The SPHERE trial aims to assess whether a health and well-being coaching and social prescribing intervention improves patient-reported health and well-being among people living with HIV who have psychosocial needs. SPHERE will be conducted across seven HIV outpatient clinics in England and is a pragmatic, two-arm, parallel group randomised controlled trial (RCT) embedding a routine assessment of psychosocial needs in HIV care. Eligibility criteria are people living with HIV aged 18 or older, available for the duration of study follow-up and scoring 16 or more on an assessment of psychosocial need: “Positive-Outcomes-11” (PO-11), covering physical, psychological, social and socioeconomic aspects of health and well-being. The RCT requires 568 participants who will be individually randomised in a 1:1 ratio to either a health and well-being coaching and social prescribing intervention or usual care. The intervention consists of up to eight coaching sessions that will be delivered by health professionals (e.g. HIV nurses) who have received specialist training to become health and well-being coaches. The trial will also include an internal pilot phase, process evaluation (to evaluate intervention feasibility, acceptability and mechanisms of action), economic evaluation (to assess the cost-effectiveness of the intervention and impact on NHS resource use) and parallel observational study (to assess subsequent development of psychosocial needs among those not initially eligible for the trial). The primary outcome is defined as achieving a reduction in PO-11 score of at least 40

ObjectivesSuccess in HIV prevention interventions, including pre-exposure prophylaxis (PrEP), among gay, bisexual and other men-who-have-sex-with-men (GBMSM) has not been replicated across all communities. The 2025 BASHH/BHIVA UK PrEP Guidelines recognizes and addresses the significant barriers and constraints that existing guidance and service delivery models place on PrEP access and equity. This paper summarizes the key guideline recommendations and the rationale supporting them.MethodsThe guidelines were developed following the methodology described in the CEG Framework for Guideline development published on the BASHH website. The writing group of clinicians, academics and community advocates incorporated input from a formal public consultation process.ResultsThe 2025 guideline includes over 90 graded recommendations. A chapter on PrEP equity and an updated chapter on PrEP suitability and risk assessment, moving away from basing PrEP eligibility on the inclusion criteria used for clinical trials, are included. Injectable PrEP has demonstrated superiority to oral PrEP but presents challenges in delivery, so improving equity in access and uptake of existing oral PrEP options was a key priority. The guidelines simplify and clarify advice on dosing for oral PrEP and recommend new event-based dosing options for all PrEP users, including quick-start double-dose PrEP for everybody. New guidance on the use of PrEP after a potential exposure is also included.ConclusionsThe PrEP guidelines purposefully highlight equity, access and the urgent requirement to meet the needs of underserved communities as a priority. These are addressed through pragmatic and groundbreaking recommendations based on careful consideration of all available evidence.

IntroductionTransgender and gender diverse people (TGD) face discrimination in workplace and healthcare settings, and worse health outcomes especially in HIV and sexual health. Pronoun sharing is recognized as good practice in promoting trans-inclusivity for both staff and service users, however it is not yet standard practice in the UK National Health Service (NHS). We conducted a national survey of NHS staff working at sexual health and HIV services to explore acceptability, barriers and facilitators to sharing and using correct pronouns.MethodsEligible participants were invited to complete an online survey between 27th October and 21st November 2023. The questionnaire, distributed through relevant mailing lists and social media, allowed for either multiple-choice, Likert scale, or free-text responses. Quantitative analyses were descriptive; qualitative analyses were loosely inductive via thematic content analysis.ResultsOur findings show that that most respondents were comfortable using and sharing pronouns. The majority of mispronouning events were "good faith" mistakes. We identified four factors which contribute to mispronouning: (1) automaticity, (2) system errors, (3) biomedical interpretations of gender, and (4) linguistic challenges. Sharing pronouns was recognized by most respondents as good professional practice and allyship.DiscussionThis study is the first to explore attitudes toward pronoun sharing in a healthcare setting. We identified barriers and facilitators at organizational, interpersonal and individual levels highlighting the multi-faceted approach that is needed to tackle this issue. Our findings provide workable targets for interventions to promote trans-inclusivity and correct pronoun use in healthcare settings.

Background:The risk of onward HIV transmission is strongly influenced by the interval between HIV infection and its diagnosis. The SELPHI trial examined whether this interval could be reduced by offering free HIV self-testing kits to men who have sex with men (MSM).Setting:Internet-based RCT of MSM aged >= 16 years, resident in England/Wales, recruited through sexual and social networking sites.Methods:The second-stage randomization of SELPHI was open to participants who used an initial free HIV self-test kit, were HIV seronegative, and reported recent condomless anal sex. They were randomized to receive a free HIV self-test kit every 3 months (repeat testing [RT] group) versus no such offer (nRT group). The primary outcome was time from randomization to a confirmed HIV diagnosis, determined from linkage to national HIV surveillance databases. The key secondary outcome was the frequency of HIV testing regardless of test modality.Results:In total, 2308 eligible participants (1161 RT, 1147 nRT) were randomized between April 2017 and June 2018, and followed for 15-27 months. The proportion of participants reporting an HIV test in the previous 3 months was much higher in the RT group (86%) than in the nRT group (39%). Overall, 16 (9 RT, 7 nRT) confirmed HIV diagnoses were observed (0.35/100 person-years), with no difference between the groups (hazard ratio = 1.27 [95% CI: 0.47 to 3.41], P = 0.63).Conclusions:Providing regular free self-testing kits to sexually active MSM was highly acceptable and markedly increased HIV testing. However, in this low incidence cohort, it did not result in a demonstrably more rapid diagnosis of incident infections.

IntroductionTrans and non-binary people have unique reproductive healthcare needs with high rates of unintended pregnancy.1,2 They also experience multiple barriers to contraceptive care, have poorer access and experience with low clinician awareness of trans-specific issues and the implications of gender affirming hormone therapy (GAHT). We aimed to better understand the contraceptive awareness, beliefs, needs and uptake in transgender men and non-binary people assigned female at birth (AFAB).MethodsWe conducted an anonymised survey of trans men and non-binary people AFAB attending a dedicated sexual health clinic between June-December 2022. Data were collected on demographics, sexual and reproductive history, healthcare experiences and contraceptive use. The survey was reviewed and validated by trans people. Descriptive analysis of quantitative data was performed on Microsoft Excel and thematic analysis was performed on qualitative data.ResultsOf the 100 respondents, 72 identified as trans men, 14 non-binary/gender queer and 14 both. 76% self-reported as white. Most respondents were aged 25–34 years. 43% (43/100) were at risk of pregnancy and 32% (14/43) of these were not using any contraception. 79% (79/100) were using GAHT and of these 44% (35/79) were potentially at risk of pregnancy. Only 50% of participants reported that contraception had been discussed on GAHT initiation, with only 16% referred for contraceptive needs. 19% of the participants indicated misconceptions about contraception. 5% participants had used emergency contraception in the past year. A strong theme identified in the qualitative feedback was the need for reliable, web-based information and resources and training to improve clinicians’ awareness of trans-health issues.DiscussionThis study identified significant contraception misconceptions, unmet contraceptive need and ongoing pregnancy risk in trans and non-binary people AFAB. There is a need for reliable, trans inclusive contraception information and for clinicians to be better able to ask about and address these issues.ReferenceKrempasky C, Harris M, Abern L, Grimstad F. Contraception across the transmasculine spectrum. American Journal of Obstetrics and Gynecology 2019;222(2):134–143. Abern L, Maguire K. Contraception knowledge in transgender individuals. Are we doing enough? Obstetrics and Gynecology 2018;131:65S.

Early UK surveillance data revealed that people living with HIV were overrepresented among cases of monkeypox (mpox). However, it remains unknown whether mpox infection is more severe in people living with well-controlled HIV. All laboratory-confirmed mpox cases presenting between May and December 2022 to one London hospital service were identified via pathology reporting systems. We extracted demographic and clinical data to allow comparison of clinical presentation and severity of mpox among people with and without HIV. We identified 150 people with mpox (median age 36 years, 99.3% male, 92.7% reporting sex with other men). HIV status was available for 144 individuals, 58 (40.3%) of whom were HIV positive (only 3/58 had CD4 cell counts <200 cells/mm3 and 5/58 had HIV RNA >200 copies/mL). People with HIV had similar clinical presentations to those without HIV, including indicators of more widespread disease, such as extragenital lesions (74.1% vs. 64.0%, p = .20) and nondermatological symptoms (87.9% vs. 82.6%, p = .38). People with HIV also experienced a similar time from onset of symptoms to discharge from all inpatient or outpatient clinical follow-up (p = .63) and total time under follow-up (p = .88) compared with people without HIV. A similar proportion of people with HIV required review in the hospital emergency department (36.2% vs. 25.6%, p = .17) or admission to hospital (19.0% vs. 9.3%, p = .09). There were no recorded deaths. In this cohort of people with mpox, there was a high prevalence of HIV coinfection, the majority of which was well-controlled. We find no evidence that people with well-controlled HIV experienced more severe mpox infection.

IntroductionWaiting lists for NHS Gender Identity Clinics (GICs) can be over 5 years (1,2) and trans people increasingly seek private sector care or self-source hormones. The GMC recommends a harm reduction approach by facilitating ‘bridging prescriptions’ of gender affirming hormone therapy (GAHT) (3). Some sexual health clinics provide advice and support with GAHTs outside of GICs or primary care. We explored the use of GAHT amongst transgender men and non-binary people assigned female at birth (AFAB) attending a dedicated sexual health service.MethodsWe conducted an anonymised survey of trans men and non-binary people AFAB attending a dedicated sexual health clinic between June-December 2022. Data were collected on demographics and use and awareness of dosing and safety of GAHTs. Thematic analysis explored reported barriers in sourcing gender-affirming care. Descriptive analysis was performed using Microsoft Excel and logistical regression analysis in STATA 17.ResultsOf the 100 respondents, 72 identified as trans men, 14 non-binary/gender queer and 14 both. 76% self-reported as white. The most common age group was 25–34 years. 79/100 (79%) reported use of gender-affirming hormones e.g. testosterone. Mean time on hormone therapy was 3 years (range 1–252 months). These were most commonly prescribed in primary care. 12/100 (12%) reported self-sourcing medications online [Figure 1]. Participants self-sourcing medications reported comparable awareness of dosage, risks and side effects to those using medical sources. 32/100 (32%) had travelled to the clinic from outside of the local commissioning authority area. Unmet need for dedicated services for advice and support was identified within the thematic analysis, particularly for services outside London.DiscussionThere is a need for local services providing support for those self-sourcing GAHTs. Sexual health services are uniquely placed to offer advice and monitoring of GAHTs, whilst engaging with this vulnerable population in wider, holistic sexual and reproductive healthcare.ReferencesNHS choices. NHS. Available at: https://www.cntw.nhs.uk/services/northern-region-gender-dysphoria-service-specialist-service-walkergate-park/waiting-list-waiting-times/ NHS choices. NHS. Available at: https://gic.nhs.uk/appointments/waiting-times/ Trans Healthcare - ethical topic. GMC - general medical council (no date). Available at: https://www.gmc-uk.org/ethical-guidance/ethical-hub/trans-healthcare

Background High levels of HIV testing in men who have sex with men remain key to reducing the incidence of HIV. We aimed to assess whether the offer of a single, free HIV self-testing kit led to increased HIV diagnoses with linkage to care. Methods SELPHI was an internet-based, open-label, randomised controlled trial that recruited participants via sexual and social networking sites. Eligibility criteria included being a man or trans woman (although trans women are reported separately); being resident in England or Wales, UK; being aged 16 years or older; having had anal intercourse with a man; not having a positive HIV diagnosis; and being willing to provide name, email address, date of birth, and consent to link to national HIV databases. Participants were randomly allocated (3:2) by computer-generated number sequence to receive a free HIV self-test kit (BT group) or to not receive this free kit (nBT group). Online surveys collected data at baseline, 2 weeks after enrolment (BT group only), 3 months after enrolment, and at the end of the study. The primary outcome was confirmed (linked to care) new HIV diagnosis within 3 months of enrolment, analysed by intention to treat. Those assessing the primary outcome were masked to allocation. This study is registered with the ISRCTN Clinical Trials Register, number ISRCTN20312003. Findings 10 111 participants (6049 in BT group and 4062 in nBT group) enrolled between Feb 16, 2017, and March 1, 2018. The median age of participants was 33 years (IQR 26-44 years); 9000 (89%) participants were White; 8118 (80%) participants were born in the UK; 81 (1%) participants were transgender men; 4706 (47%) participants were university educated; 1537 (15%) participants had never been tested for HIV; and 389 (4%) participants were taking pre-exposure prophylaxis. At enrolment, 7282 (72%) participants reported condomless anal sex with at least one male partner in the previous 3 months. In the BT group, of the 4511 participants for whom HIV testing information was available, 4263 (95%) reported having used the free HIV self-test kit within 3 months. Within 3 months of enrolment there were 19 confirmed new HIV diagnoses (0 center dot 31%) in 6049 participants in the BT group and 15 (0 center dot 37%) of 4062 in the nBT group (p=0 center dot 64). Interpretation The offer of a single, free HIV self-test did not lead to increased rates of new HIV diagnoses, which could reflect decreasing HIV incidence rates in the UK. Nonetheless, the offer of a free HIV self-testing kit resulted in high HIV testing rates, indicating that self-testing is an attractive testing option for a large group of men who have sex with men. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Introduction Trans and non-binary people face significant health inequalities. They are less likely than cisgender people to attend sexual health clinics, less likely to test for HIV and have poorer uptake of contraception. We describe our experience of delivering a sexual and reproductive health service designed specifically for trans and non-binary people in London. Methods We analysed data from self-completed questionnaires from service users attending the clinic between 7th May 2019 and 11th January 2022. Data collected includes demographic information, reason for attendance, hormone use and source, sexual activity and HIV status. Patient feedback data were also analysed. Results 1078 questionnaires were analysed. Mean age was 30 (age range 14-78). 31% identified as trans men, 22% gender queer/non-binary, 21% as trans women, 14% as male and 10% as female. 35% lived locally, 50% came from other parts of London and 15% travelled from outside London. 57% attended for hormone injections/advice, 25% for STI testing/treatment and 10% for counselling. 80% of were taking cross-sex hormones with 23% self-sourcing from the internet. Feedback was universally positive with 98% being ‘pleased with the service’ and 100% would strongly recommend to a friend. Discussion We have demonstrated an effective and acceptable trans-inclusive holistic service that meets both sexual health and wider physical and mental health needs. The fact that many people travel long distances to the clinic demonstrates the need for more local trans specific or trans inclusive services and we would encourage other clinics to deliver similar models of care.

OBJECTIVES:We report the frequency of previous HIV testing at baseline in men who have sex with men (MSM) who enrolled in an HIV self-testing (HIVST) randomized controlled trial [an HIV self-testing public health intervention (SELPHI)]. METHODS:Criteria for enrolment were age ≥ 16 years, being a man (including trans men) who ever had anal intercourse (AI) with a man, not being known to be HIV positive and having consented to national HIV database linkage. Using online survey baseline data (2017-2018), we assessed associations with never having tested for HIV and not testing in the previous 6 months, among men who reported at least two recent condomless AI (CAI) partners. RESULTS:A total of 10 111 men were randomized; the median age was 33 years [interquartile range (IQR) 26-44 years], 89% were white, 20% were born outside the UK, 0.8% were trans men, 47% were degree educated, and 8% and 4% had ever used and were currently using pre-exposure prophylaxis (PrEP), respectively. In the previous 3 months, 89% reported AI and 72% reported CAI with at least one male partner. Overall, 17%, 33%, 54%, and 72% had tested for HIV in the last 3 months, 6 months, 12 months and 2 years, respectively; 13% had tested more than 2 years ago and 15% had never tested. Among 3972 men reporting at least two recent CAI partners, only 22% had tested in the previous 3 months. Region of residence and education level were independently associated with recent HIV testing. Among current PrEP users, 15% had not tested in the previous 6 months. CONCLUSIONS:Most men in SELPHI, particularly those reporting at least two CAI partners and current PrEP users, were not testing in line with current UK recommendations. The results of the trial will inform whether online promotion of HIVST addresses ongoing testing barriers.

Background The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. Methods The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA < 200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. Findings Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2.0 years (IQR 1.1-3.5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1.0 years (IQR 0.4-2.9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0.23 per 100 couple-years of follow-up). Interpretation Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

Globally, HIV criminalisation continues to exacerbate and perpetuate HIV stigma and discrimination. Over 70 countries have laws that specifically criminalise HIV non-disclosure, exposure or transmission, and 39 countries have used existing criminal laws to prosecute people living with HIV. Society and criminal justice systems have failed to keep up with scientific advances of recent years and, in particular, our understanding of the powerful impact anti-retroviral therapy has on reducing HIV transmission risk. We now know that individuals on effective HIV therapy with an undetectable viral load do not transmit the virus to their sexual partners. This knowledge has not, as yet, translated into any significant change to the application of criminal law. The era of U=U (Undetectable = Untransmittable) should support our ability to use scientific evidence to end the criminalisation of HIV and the disproportionate impact this has on marginalised communities and those less able, for whatever reason, to achieve and maintain an undetectable viral load. Disclosure No significant relationships.

The objective of this study was to evaluate a service improvement project offering HIV testing through either self-testing or self-sampling in an online sexual health service by measuring type of test chosen and the reason for this choice. We created a web-page offering choice of online self-sampling or self-testing with information on the advantages and disadvantages of both methods. Anyone aged over 18 years resident in England, Scotland or Wales could order either type of test. We describe the characteristics of users, the tests chosen and the reasons for the choice. A total of 1502 HIV testing orders were placed and 1466 (97.6%) testing kits were dispatched after exclusion of multiple orders by the same user. Sixty-seven per cent of users chose self-testing (n = 984) and the rest chose self-sampling (n = 482, 32.9%). The most frequent reasons for choosing self-testing were: immediate results (n = 264, 46.9%), ability to complete the test themselves (n = 168, 29.8%), less blood required (n = 67, 11.9%) and the privacy of testing at home (n = 55, 9.8%). Public sector provision of self-testing as an adjunct to clinic-based HIV testing services is likely to be highly acceptable to UK populations. However, a proportion will prefer self-sampling, and maintaining choice of testing modality is important.

The guidelines are aimed at clinical professionals directly involved in, and responsible for, HIV prevention, and at community advocates and organisations responsible for supporting HIV prevention strategies in those at risk of HIV acquisition. A detailed review of the evidence base is included in Section 4. Sections 5–7 are intended to offer practical guidance in risk assessment, starting PrEP, ongoing management while on PrEP and stopping PrEP. We recognise the importance of these guidelines being inclusive and relevant to all, regardless of sexuality or gender identity or expression. For the sake of brevity in the main text of the guidelines, phrases such as "men who have sex with men" refer to cis-gender or non-binary or gender-queer men who have sex with men and "heterosexual men and women" refer to cis-gender or non-binary or gender-queer men and women who have heterosexual sex. Where sections are specifically relevant to trans people, we identify this using the terms trans people, trans men or trans women. The multidisciplinary guideline writing group developed the guidelines based on the process outlined in the BHIVA Guidelines Development Manual 1. All members of the group underwent GRADE training. We undertook a comprehensive literature review on PrEP and HIV prevention using the PICO question shown below. The recommendations are the result of a series of face-to-face and virtual meetings of the writing group and a meeting of community activists and organisations who commented on a draft of the guidelines in May 2017. The writing group also reviewed and incorporated input from the public consultation process. The literature review search was from January 2004 to May 2016. Medline, Embase and Cochrane databases were searched. Only papers in English were included and animal studies were excluded. In addition, although the formal literature review was not repeated, subsequent evidence published between May 2016 and July 2017 that the writing group felt was relevant has been included. A Grade 1 recommendation is a strong recommendation to do (or not do) something, where benefits clearly outweigh risks (or vice versa) for most, if not all, patients. Most clinicians and patients would want to follow a strong recommendation unless there is a clear rationale for an alternative approach. A strong recommendation usually starts with the standard wording "We recommend". A Grade 2 recommendation is a weaker or conditional recommendation, where the risks and benefits are more closely balanced or are more uncertain. Alternative approaches or strategies may be reasonable depending on the individual patient's circumstances, preferences and values. A weaker or conditional recommendation usually starts with the standard wording "We suggest". The strength of a recommendation is determined not only by the quality of evidence for defined outcomes, but also the balance between desirable and undesirable effects of a treatment or intervention, differences in values and preferences, and where appropriate, resource use. Each recommendation concerns a defined target population and is actionable. In addition to graded recommendations, the writing group has also included good practice points (GPPs). GPPs are recommendations based on the clinical judgement and experience of the working group and feedback from community and public consultation. GPPs emphasise an area of important clinical practice for which there is not, nor is there likely to be, any significant research evidence. They address an aspect of treatment and care that is regarded as such sound clinical practice that healthcare professionals are unlikely to question it, and where the alternative recommendation is deemed unacceptable. It must be emphasised that GPPs are not an alternative to evidence-based recommendations. The guideline writing group included representation from Terrence Higgins Trust and NAZ. In order to widen the stakeholder involvement, a meeting of community activists and organisations was held in May 2017, when feedback was sought on the content of the draft guidelines and recommendations prior to wider public consultation. We acknowledge the following for their helpful contributions: Yusef Azad (NAT), Takudzwa Mukiwa (THT), Will Nutland (Prepster), Greg Owen (I Want PrEP Now), Michelle Ross (CliniQ), Sophie Strachan (Sophia Forum), Marc Thompson (Prepster/Black Out UK) and George Valiotis (HIV Scotland). The guideline writing group recognises that although the PrEP trials used tenofovir disoproxil fumarate (TDF), increasingly other salts of tenofovir disoproxil (including maleate, succinate and phosphate) will be used in generic formulations. We have therefore used the acronym TDF-FTC where Truvada was used in a trial and TD-FTC to denote all other (generic) forms of tenofovir disoproxil and emtricitabine. The iPrEx study 1 was a Phase 3, randomised, double blind, placebo-controlled, multi-centre trial conducted among 2499 MSM and trans male-to-female adults (n = 339) in Peru, Ecuador, Brazil, Thailand, South Africa and the United States. Participants were randomly assigned to either a daily dose of TDF-FTC (1251 participants) or placebo (1248 participants). Primary outcome was HIV infection with a total of 3324 person-years of follow-up. Over the course of the study, 100 participants became infected with HIV; 36 in the TDF-FTC group and 64 in the placebo group, representing a 44% (95% confidence interval [CI] 15–63) reduction in HIV incidence using a modified intention-to-treat (ITT) analysis, excluding those confirmed HIV positive at randomisation. Efficacy was higher in the per-protocol analysis; at visits where adherence was >50% by self-report and pill count/dispensing, efficacy was 50% (95% CI 18–70). The PROUD study was a Phase 3, randomised, open-label, multi-centre trial conducted in 544 MSM at 13 sexual health clinics in England 2. Participants were randomly assigned to a daily dose of TDF-FTC immediately (275 participants), or after a deferral period of 12 months (269 participants). Primary outcomes were time to accrual of 500 participants and retention at 12 and 24 months; HIV infection was a secondary outcome. At interim review, the DSMB recommended that all study participants should be offered study drug. A total of 23 participants became infected with HIV over the course of the study: three in the daily TDF-FTC group and 20 in the deferred (no-PrEP) group, representing a rate difference in HIV infection of 7.8 per 100 person-years (90% CI 4.3–11.3) The relative risk reduction was 86% (90% CI 64–96%) and the number needed to treat over 1 year to prevent one HIV infection was 13 (90% CI 9–23). The IPERGAY study was a Phase 3 double-blind, randomised, multi-centre trial conducted among 414 MSM in France and Canada 3. Participants were randomly assigned to either receiving an on-demand regimen of TDF-FTC (206 participants) or placebo (206 participants). The on-demand regimen involved taking a double dose of TDF-FTC 2–24 h before sex, and a daily dose during periods of sexual risk and for 48 h (two doses) after ceasing sexual risk. Participants were followed up every 8 weeks for HIV testing and risk-reduction advice, and every 6 months for sexually transmitted infection (STI) testing for a total of 431 person-years of follow-up. Primary endpoint was HIV infection. At interim review, the placebo group was discontinued and all study participants were offered study drug. Over the course of the study, 16 people became infected with HIV: two in the TDF-FTC group and 14 in the placebo group, representing a relative risk reduction of 86% (95% CI 40–98%) in the ITT analysis. One Phase 2 safety trial, the CDC MSM Safety Trial 4, compared tenofovir (TDF) to placebo in a randomised, double-blind, placebo-controlled, wait-listed design among 400 HIV-negative MSM. Participants were randomly assigned in a 1:1:1:1 design to receive TDF or placebo immediately or after 9 months. Main endpoints were safety and behavioural outcomes. There were no infections among those taking active drug. Seven participants seroconverted: four in the placebo arm and three among delayed-arm participants who were not on the study drug. An eighth participant was HIV positive at enrolment. Two further smaller studies include a pilot feasibility and acceptability study, Project PrEPare, which recruited 58 young MSM aged 18–22 years in the United States. Participants were randomly allocated to receive a behavioural intervention alone, the behavioural intervention and PrEP (TDF-FTC) or the behavioural intervention and placebo. There were no seroconversions among the 58 participants 5. The IAVI Kenya Study was a small safety and adherence study conducted among Kenyan MSM and female commercial sex workers (CSWs). Sixty-seven MSM and five female CSWs were randomly assigned to daily TDF-FTC or placebo, or intermittent (Monday, Friday and within 2 h after sex) TDF-FTC or placebo in a 2:1:2:1 ratio. There was one seroconversion in the placebo arm 6. The iPrEx Open-label Extension (iPrEx-OLE) 7 enrolled 1603 HIV-negative men and 339 (14%) trans women who have sex with men who were previously part of PrEP studies (iPrEx, ATN082/Project PrEPare and CDC MSM Safety Trial). Participants were offered daily TDF-FTC and were followed up for 72 weeks after enrolment. Uptake was high at 76%, and this was higher among those reporting condomless receptive anal intercourse and those who were herpes simplex-2 virus (HSV-2) seropositive, suggesting use during periods of risk. HIV incidence was 1.8 infections per 100 person-years, compared with 2.6 infections per 100 person-years in those who concurrently did not choose PrEP (hazard ratio [HR] 0.51, 95% CI 0.26–1.01, adjusted for sexual behaviours) 7. Examination of drug levels by dried blood spot testing was extrapolated to pill taking and compared to HIV incidence each quarter. No seroconversions were seen when drug levels were compatible with taking four or more pills per week. The IPERGAY Open-label Extension (IPERGAY-OLE) enrolled 362 individuals to take on-demand TDF-FTC and followed them for a median of 11.7 months, of whom 299 (83%) completed follow-up with a single HIV infection (0.19 per 100 person-years, 95% CI 0.01–1.08) 8. A community-based clinic in San Francisco screened 1249 MSM (and three trans men) and offered PrEP with TDF-FTC with 95.5% uptake. Condomless sex was reported by 93% at enrolment. After a maximum of 16 months' follow-up there were no new HIV infections in the men enrolled in the programme 9. At the time of writing there have been three case reports of HIV transmissions in MSM taking PrEP despite apparent confirmed adherence. Two individuals were infected with resistant virus and, in one case, transmission occurred with wild-type virus sensitive to both tenofovir and emtricitabine 10. Efficacy of PrEP is highly dependent on adherence, with a meta-analysis of PrEP studies 12 demonstrating that adherence is a significant moderator of PrEP effectiveness. The higher the levels of adherence to oral PrEP in the study population, as measured by detectable drug, the greater the efficacy. In the iPrEX study, adherence was monitored using pill count and self-reported adherence. Pharmacokinetic plasma and intracellular drug-level sampling was conducted in a pre-specified subgroup analysis where subjects with HIV infection were matched with two controls selected from seronegative subjects. In those who had detectable drug levels of TDF-FTC, the reduction in HIV incidence was 92% (95% CI 40–99%) compared to those who had no drug detected 1, suggesting that a high level of adherence is associated with a high level of efficacy. In the PROUD study, adherence was monitored using prescription data, self-reported adherence and drug levels in a convenience sample of study participants. Overall, sufficient study drug was prescribed for 88% of the total follow-up time and tenofovir was detected in all samples taken from 52 participants who reported taking study drug within the preceding 3 days 2. In the IPERGAY study, adherence was monitored using pill counts, self-reported adherence and drug levels in a subset of 113 participants. Of participants in the active treatment group who had drug levels measured, protective drug levels of tenofovir were detected in 86%. However, computer-assisted interview (CASI) data collected in 319 participants in the randomised phase suggested that only 43% of people took study drug correctly during last sexual intercourse, 29% took a suboptimal dose and 28% did not take the study drug at all 3. In the open-label phase, adherence in 362 men completing 1617 CASI returns reported 50% of men taking study drug correctly during last sexual encounter, 24% taking a suboptimal dose and 26% taking no study drug at all 8. Comparison of adherence to different regimens of TDF-FTC PrEP has been investigated in MSM in the HPTN 067 (ADAPT) study. The study recruited MSM and trans women in Harlem (New York, USA) and Thailand and heterosexual women in South Africa. Following a 4-week phase of daily dosing, participants were randomly assigned 1:1:1 to one of three regimens: daily dosing ("daily") or one tablet twice a week and one tablet post sex ("time driven") or one tablet 24–48 h before sex and one tablet within 2 h after sex ("event-based"). Results from 178 Thai MSM showed that coverage (defined as taking more than one pill in the 4 days before sex and more than one pill in the 24 h afterwards) was significantly higher in the daily (85% of events covered) and time-driven (84%) arms than in the event-driven arm (74%). Two seroconversions occurred in the 4 week pre-randomisation phase 13. In 179 MSM in Harlem, figures were 66%, 47% and 52%, respectively, with one seroconversion in the pre-randomisation phase and one in the randomised phase 14. Adherence was higher in the daily-dose arms: in Thailand, 85% of daily doses, 79% of twice-weekly doses, and 65% of event-driven doses were taken as prescribed. In Harlem, the respective figures were 65%, 46% and 41%. Although these represent two diverse populations of MSM in different settings, the study demonstrated similar coverage of sex acts for daily and non-daily regimens with both groups demonstrating lower adherence and coverage rates for the event-driven approach. Higher coverage of events in the Thai MSM was associated with older age and higher level of education. Use of stimulant drugs and higher sexual frequency was associated with lower coverage 15. To date, studies of TDF-FTC PrEP suggest short-term safety. A meta-analysis of PrEP studies 12 demonstrated no difference in the proportions of adverse events comparing PrEP to placebo across 10 placebo-controlled RCTs (odds ratio [OR] 1.01, 95% CI 0.99–1.03, P = 0.27) with no differences seen in subgroup analysis that included mode of acquisition, adherence, sex, drug regimen, dosing or age. No differences were seen in grade 3 or 4 adverse events comparing PrEP and placebo groups across 11 placebo-controlled RCTs (risk ratio [RR] 1.02, 95% CI 0.92–1.13, P = 0.76). Results were not presented by subgroup. In the iPrEx study, there was no difference in reported adverse events between the two study arms: 867/1251 (67%) of participants in the TDF-FTC arm reported any adverse event, compared to 877/1248 (70%) in the control arm. Both arms reported similar rates of grade 3 and 4 adverse events: 151/1251 (12%) of TDF-FTC participants compared to 164/1248 (13%) of control-arm participants 1. There was no difference in permanent or temporary discontinuation of study drug between the two arms: 25/1251 (2%) permanent discontinuations in the intervention arm compared to 27/1248 (2%) in the placebo arm and a total of 79/1251 (6%) permanent or temporary discontinuations in the intervention arm compared to 72/1248 (6%) in the placebo arm. However, nausea was more common among those taking TDF-FTC compared to placebo in the first month (95% vs. 5%). Depression-related adverse events were the most common severe or life-threatening adverse events reported in iPrEx, but were not associated with being randomly assigned to TDF-FTC (OR 0.66, 95% CI 0.35–1.25) 16. In the PROUD study, 21/275 participants (8%) interrupted or missed study drug doses because of adverse events, the commonest of which were headache and nausea 2. In IPERGAY, drug-related gastrointestinal adverse events were reported more commonly in the TDF-FTC group compared to the placebo group (14% vs. 5%, P = 0.002), but there was no difference in the frequency of grade 3 or 4 adverse events 3. PrEP trials have shown modest, but statistically significant declines in renal function with administration of daily TDF-FTC, but the incidence of serious renal events was very low and mostly reversible. In PROUD, three participants interrupted drug due to elevated creatinine concentrations (two were classed as mild elevation, defined as 1.1–1.3 times the upper limit of normal [ULN], and one as moderate, 1.4–1.8 ULN), although the most likely explanation in one man was recreational drug use and the other two men were older with comorbidities 2. In the IPERGAY study, 18% of active drug participants experienced elevated creatinine levels compared to 10% of placebo group (P = 0.03). All, but one were mild and transient and none led to discontinuation of study drug 3. In the iPrEx study, use of TDF-FTC was associated with a mild non-progressive decrease in estimated creatinine clearance (CrCl) of 2.4% from baseline, which was reversible 14. Creatinine elevations of >1.1 ULN were similar between active and placebo arms, occurring in 32 (2.6%) in the active arm and 24 (2.2%) in the placebo arm (RR 1.35, 95% CI 0.80–2.3). Most excess creatinine elevations in the active arm of the study (median follow-up 72 weeks) occurred at 12–24 weeks and all occurred at <48 weeks. Proteinuria by dipstick was detected regularly (613/5081 [12%] dipsticks performed), but there was no between-group difference in the proportion of participants ever positive for proteinuria (20% placebo vs. 21% TDF-FTC; P = 0.62). In addition, the positive predictive value of proteinuria in predicting a confirmed creatinine elevation was poor at 0.7% 14. In iPrEx-OLE the probability of CrCl falling to ≤60 mL/min at least once over the first year on PrEP was low, but was more likely when participants started PrEP at older ages (>40 years) or with a starting CrCl ≤90 mL/min 15. For participants under 40 years of age, the mean decline in CrCl over the duration of the study (median 72 weeks) was modest (−2.6%) and no patients experienced a CrCl drop to ≤60 mL/min, even in those with full adherence to daily dosing, indicating that annual monitoring of renal function in this group should be sufficient. However, being aged >40 years or with a lower baseline creatinine clearance (≤90 mL/min) at initiation of PrEP were independently associated with a risk of CrCl falling to ≤60 mL/min, especially with daily dosing. This suggests that more frequent renal monitoring on PrEP may be required in older PrEP users (>40 years) and in those with marginal renal function at baseline, even if there are no other concomitant risk factors for renal disease. In an iPrEx sub-study of 500 participants who underwent 6-monthly DEXA scans to assess bone mineral density (BMD), a small net decrease in BMD of 0.7–1% was seen among those randomly assigned to TDF-FTC (n = 247) compared to placebo (n = 256) after 24 weeks in both spine and total hip measures 17. There are no long-term data on bone health for people on TDF-FTC PrEP. In the CDC MSM study, in multivariate analysis, back pain was associated with use of TDF and also a small decrease in BMD among a subset of 184 men in the San Francisco site. However, TDF use was not associated with bone fractures 18. In the iPrEx trial, FTC-related drug resistance developed in two participants who had unrecognised acute HIV infection at baseline 19. These individuals had a negative antibody test before starting PrEP, but later tested positive. In the PROUD study, two of the three participants with a positive HIV test at enrolment or the 4-week visit had FTC-related drug resistance; no resistance was detected in participants who acquired HIV post-randomisation 2. In IPERGAY, none of the incident HIV infections post-randomisation demonstrated resistance mutations to study drug 3. In a meta-analysis, Fonner et al. reviewed results from six trials that reported cases of FTC or TDF drug resistance using standardised genotypic laboratory assays 12. Although the only study of MSM included in this analysis was iPrEx, the risk factors associated with development of drug resistance will be similar in MSM and people who have heterosexual sex. The risk of developing an FTC-related mutation among those acutely infected with HIV at enrolment was significantly higher in the group randomly allocated to receive TDF-FTC compared to placebo (risk ratio 3.72, 95% CI 1.23–11.23, P = 0.02). The risk of a TDF-related mutation was not statistically different between PrEP and placebo, regardless of PrEP regimen, among those acutely infected at enrolment. Additionally, six (2%) TDF- or FTC-resistant infections occurred among 544 post-randomisation HIV infections: five in PrEP groups and one in a placebo group. Numbers were too small to calculate a pooled relative risk. Risk behaviour has been measured using outcomes including STI diagnoses, condom use and sexual partner numbers. The most clinically relevant outcome is STI diagnoses, not least because the other two indicators are self-reported and, as such, subject to reporting bias. In the placebo-controlled trials, one purpose of the placebo is to control for behaviour, and it is not possible to comment on the impact of PrEP on behaviour, as participants do not know if they are on active drug. However, it is possible to evaluate the impact of the risk-reduction support provided to all participants, and there were demonstrable benefits in iPrEx, the CDC MSM Safety Trial, but not the IAVI Kenya study. In the iPrEx study, both PrEP and placebo groups reported increased condom use over the course of the study and reported condom use did not differ between the arms (P = 0.36) 1. The number of reported receptive sexual intercourse partners in both arms also declined over the course of the study, with no significant difference in the number of partners reported in each group at each time point (P = 0.97) 1. The reduction in risk behaviours may reflect the fact that the majority of iPrEx participants came from populations with little access to risk-reduction support. In IPERGAY, there were no significant differences between TDF-FTC and placebo groups in the proportion of condomless receptive anal sex (P = 0.40) and incident STIs (P = 0.10). There was a slight but significant decrease in the number of sexual partners in the previous 2 months in the placebo group compared to the TDF-FTC group (7.5 vs. 8, P = 0.001) 3, 20. In the CDC MSM Safety Trial (also placebo-controlled), mean number of sexual partners in the previous 3 months and the proportion reporting condomless anal sex declined over 24 months of follow-up. The IAVI Kenya study, which included MSM, was the only trial to report an increase in study partners from baseline to follow-up, but partners may have been underreported at baseline 6. In the open-label PROUD study, in which participants knew they were taking PrEP and that it was at least partially effective, there was no difference between the immediate and deferred (no-PrEP) groups in the total number of sexual partners (P = 0.57) in the 3 months prior to the 1-year questionnaire, but a greater proportion of the immediate group reported receptive anal sex without a condom with 10 or more partners compared to the deferred group (21% vs. 12%, P = 0.03). There was no difference in the frequency of bacterial STIs during the randomised phase (P = 0.74) 2. In the iPrEx-OLE study, both groups reported decreases in reported condomless receptive anal intercourse from 34% (377/1115) to 25% (232/926 P = 0.006) among those accepting PrEP and from 27% (101/369) to 20% (61/304; P = 0.03) in the group who declined PrEP. Conversely, in IPERGAY-OLE there was a much higher baseline rate and a significant increase in reported condomless sex at last receptive anal intercourse from 77% at baseline to 86% at 18 months (P = 0.003 for trend) 8. Examination of three different trajectories of condom use (low, medium and high) and four of PrEP use over time in IPERGAY-OLE shows that in the majority of men, declines in condom use were compensated by increased on-demand PrEP use, but in a minority of men this was not the case. Compensation by using on-demand PrEP was lower in younger men for all three condom trajectories 21. In a large observational cohort study of MSM PrEP in a community-based clinic in San Francisco, self-reported condom use for different sub-cohorts of men taking PrEP for periods of 1–16 months was unchanged in 38–61%, increased in 5–12% and reduced in 16–48% 9. Both the PROUD and IPERGAY studies documented high levels of bacterial STIs in MSM throughout the course of follow-up. Within IPERGAY, participants were screened at enrolment and every 6 months during follow-up for chlamydia and gonorrhoea (with triple site nucleic acid amplification tests) and syphilis 10. Of participants receiving TDF-FTC, 41% acquired a new STI during follow-up, compared to 33% in the placebo arm; most STIs were rectal and 10% acquired a new syphilis infection 3. Similar results were observed within the PROUD study where 3- to 6-monthly STI screening was offered and the proportions with a bacterial STI were 50% and 57% of men diagnosed with an STI, respectively, in the deferred and immediate treatment arms of the study (P = 0.74). Similarly to IPERGAY, 10% of individuals in PROUD acquired a new syphilis infection 2. In iPrEx OLE the incidence of syphilis was similar in both groups, although numerically higher among PrEP users (7.2/100 person-years compared to 5.4/100 person-years in non-PrEP users, HR 1.35, 95% CI 0.83–2.19). In IPERGAY, incidence rate of first STI was 35.2 per 100 person-years in the double-blind phase, and 40.6 per 100 person-years in the open-label phase 3. Incident hepatitis C has also been reported in clinical trials and PrEP access projects. In Amsterdam, HIV-negative MSM who enrolled in the Amsterdam PrEP demonstration project had considerably higher hepatitis C virus (HCV) prevalence at 4.8% than HIV-negative MSM in the general Amsterdam STI clinic survey at 0.3–1.2% 22. Genetic analyses suggested that circulating HCV strains in HIV-negative men starting PrEP were similar to those in local HIV/HCV co-infected MSM. In the PROUD study, 5/160 (3.1%) participants who had tested on one or more occasions for HCV had incident HCV infection (3.1%). There were three incident HCV infections in the immediate arm and two in the deferred arm 2. In IPERGAY, overall, there were five incident HCV infections 3 suggesting that HIV-negative men on PrEP are at risk of HCV infection and should undergo regular testing for HCV while on PrEP. Two RCTs have demonstrated the efficacy of daily oral PrEP in preventing HIV acquisition among heterosexual individuals. One Phase 3 RCT, Partners PrEP 1, assessed the efficacy of daily oral TDF vs. TDF-FTC vs. placebo in serodifferent heterosexual couples in East Africa and one Phase 3 RCT, TDF-2 2, evaluated TDF-FTC vs. placebo in sexually active heterosexual adults at high risk of HIV acquisition in Botswana. No studies have evaluated the efficacy of an on-demand PrEP regimen in heterosexuals and to date there have been no RCTs undertaken in heterosexual men and women in high-income countries. Although there is no reason to think the biological efficacy would be different, given the lack of RCTs in heterosexuals in high-income countries, it remains difficult to generalise the finding of high PrEP efficacy from these two trials in sub-Saharan Africa (SSA) to the UK because HIV incidence is much lower, and no well-defined group of heterosexuals with high HIV incidence can be identified in national surveillance data. Furthermore, there are likely to be differences in cultural beliefs and sociodemographic circumstances that influence adherence and efficacy and further complicate any extrapolation of the data. Two RCTs (FEM-PrEP 3 and VOICE 4), both in heterosexual women in SSA, reported low efficacy rates of daily oral PrEP. In both cases, the studies were well conducted and the null results, and inconsistency of the results when compared to TDF-2 and Partners PrEP, are primarily attributed to low adherence (measured using drug levels) to the study drug in the intervention arm. Partners PREP was a double-blind, placebo-controlled Phase 3 RCT following 4747 heterosexual couples, comparing single and dual agent PrEP (TDF vs. TDF-FTC) with placebo conducted from 2008 to 2010 1. Participants were sexually active serodifferent heterosexual couples in Uganda and Kenya. HIV-negative participants were aged between 18 and 65 years, sexually active with an HIV-positive partner (≥6 episodes of vaginal intercourse with HIV-positive partner in the past 3 months) with no chronic HBV infection. HIV-negative women who were breastfeeding, pregnant or planning to become pregnant were excluded from the study. The study also excluded HIV-negative participants with glycosuria or proteinuria, ongoing therapy with certain drugs, and a history of pathological bone fractures not related to trauma. HIV-positive sexual partners were >18 years old, sexually active, with CD4 cell counts ≥250 cells/mL, no history of AIDS-defining illnesses and not using antiretrovirals (ARVs). The HIV incidence in the control arm was 1.99 per 100 person-years. Overall, the study found the efficacy of PrEP using TDF alone was 67% (95

Objectives Pre-exposure prophylaxis (PrEP) is a highly effective method of HIV prevention for men who have sex with men (MSM). However, uncertainty remains around the optimal eligibility criteria for PrEP, specifically whether there are subgroups at low risk of HIV for whom PrEP might not be warranted. Methods PROUD was an open-label waitlist trial design that randomised MSM attending participating sexual health centres in England to receive PrEP immediately (IMM) or after a deferral period of 1 year (DEF). This analysis is based on participants who were randomised to the deferred arm, when they did not have access to PrEP. HIV incidence was compared between subgroups defined by baseline characteristics. Results Overall, 21 participants acquired HIV infection over 239.3 person-years (PY) follow-up, yielding an incidence rate of 8.8/100 PY (95% CI 5.4 to 13.4). Two highly significant predictors for HIV acquisition were identified. Men with a self-reported diagnosis of syphilis, rectal chlamydia (CT) or rectal gonorrhoea (GC) in the previous 12 months had an incidence of 17.2/100 PY (95% CI 9.7 to 28.5); those reporting receptive anal intercourse without a condom (ncRAI) with two or more partners in the previous 3 months had an incidence of 13.6/100 PY (95% CI 7.9 to 21.7). The incidence rate among participants lacking both of these risk factors was 1.1/100 PY (1/87.6, 95% CI 0.03 to 6.4). Conclusions The high HIV incidence in PROUD suggests that most participants appropriately judged their need for PrEP. Eligibility criteria for a PrEP programme can therefore be broad, as in the current guidelines. However, a recent history of syphilis or rectal CT/GC, or multiple ncRAI partners indicates a high imminent risk of HIV infection. MSM with any of these characteristics should be offered PrEP as a matter of urgency.