The effect of combination prevention strategies on HIV incidence among gay and bisexual men who have sex with men in the UK: a model-based analysis.

BACKGROUND: In the UK, the number of new HIV diagnoses among gay and bisexual men who have sex with men (GBMSM) has decreased substantially. We aimed to understand the contribution of different interventions in reducing HIV incidence so far; to estimate future HIV incidence with continuation of current policies and with further scaling up of current interventions; and to estimate the maximum additional annual cost that should be spent towards these interventions for them to offer value for money. METHODS: We calibrated a dynamic, individual-based, stochastic simulation model, the HIV Synthesis Model, to multiple sources of data on HIV among GBMSM aged 15 years or older in the UK. Primarily these were routine HIV surveillance data collected by the UK Health Security Agency. We compared HIV incidence in 2022 with the counterfactual incidence: if HIV testing rates stopped increasing in 2012 and the policy of antiretroviral therapy (ART) at diagnosis was not introduced in mid-2015; if pre-exposure prophylaxis (PrEP) was not introduced; if condom use was low from 2012 in all GBMSM, at levels similar to those observed in 1980; and in the first and second scenario combined. We also projected future outcomes under the assumption of continuation of current policies and considering increases in PrEP and HIV testing uptake and a decrease in condomless sex. FINDINGS: Our model estimated a 77% (90% uncertainty interval [UI] 61-88) decline in HIV incidence since around 2014, with an estimated 597 infections ([90% UI 312-956]; 1·1 per 1000 person-years [90% UI 0·6-1·8]) in men aged 15-64 years in 2022. Both PrEP introduction and increased HIV testing with ART initiation at diagnosis each had a substantial effect on HIV incidence. Without PrEP introduction, we estimate there would have been 2·16 times the number of infections that actually occurred (90% UI 1·06-3·75) between 2012 and 2022; without increased HIV testing and ART initiation at diagnosis there would have been 2·18 times the number of infections that actually occurred (1·18-3·60), and if condomless sex was at the levels before the HIV epidemic, there would have been 2·27 times the number of infections that actually occurred (0·9-5·4). If rates of testing, ART use, and PrEP use remain as they are currently, there is a predicted decline in incidence to 388 HIV infections in 2025 (90% UI 226-650) and to 263 (137-433) in 2030. Increases in HIV testing and PrEP use were predicted to accelerate the decline in HIV incidence. Given the quality-adjusted life-year (QALY) benefit and a cost-effectiveness threshold of £30 000 per QALY gained, in order to be cost-effective an additional £1·62 million could be spent per year to increase testing levels by 34% (90% UI 25-46) and PrEP use by 55% (10-107). To achieve that, a 16% reduction in the cost of delivery of testing and PrEP would be required. INTERPRETATION: Combination prevention, including a PrEP strategy, played a major role in the reduction in HIV incidence observed so far in the UK among GBMSM. Continuation of current activities should lead to a continued decline; however, it is unlikely to lead to reaching the target of fewer than 50 HIV infections per year among GBMSM by 2030. It will be important to reduce costs for testing and PrEP for their continued expansion to be cost-effective. FUNDING: National Institute for Health Research under its Programme Grants for Applied Research Programme and Medical Research Council-UK Research and Innovation.

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation.

BACKGROUND: In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain. METHODS: In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs. FINDINGS: Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex. INTERPRETATION: This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised. FUNDING: National Institute for Health Research.

Can text messages increase safer sex behaviours in young people? Intervention development and pilot randomised controlled trial.

BACKGROUND: Younger people bear the heaviest burden of sexually transmitted infections (STIs). Partner notification, condom use and STI testing can reduce infection but many young people lack the knowledge, skills and confidence needed to carry out these behaviours. Text messages can provide effective behavioural support. The acceptability and feasibility of a randomised controlled trial of safer sex support delivered by text message are not known. OBJECTIVES: To assess the acceptability and feasibility of a randomised controlled trial of a safer sex intervention delivered by text message for young people aged 16-24 years. DESIGN: (1) Intervention development; (2) follow-up procedure development; (3) a pilot, parallel-arm randomised controlled trial with allocation via remote automated randomisation (ratio of 1 : 1) (participants were unmasked, whereas researchers analysing samples and data were masked); and (4) qualitative interviews. SETTING: Participants were recruited from sexual health services in the UK. PARTICIPANTS: Young people aged 16-24 years diagnosed with chlamydia or reporting unprotected sex with more than one partner in the last year. INTERVENTIONS: A theory- and evidence-based safer sex intervention designed, with young people's input, to reduce the incidence of STIs by increasing the correct treatment of STIs, partner notification, condom use and STI testing before unprotected sex with a new partner. The intervention was delivered via automated mobile phone messaging over 12 months. The comparator was a monthly text message checking contact details. MAIN OUTCOME MEASURES: (1) Development of the intervention based on theory, evidence and expert and user views; (2) follow-up procedures; (3) pilot trial primary outcomes: full recruitment within 3 months and follow-up rate for the proposed primary outcomes for the main trial; and (4) participants' views and experiences regarding the acceptability of the intervention. RESULTS: In total, 200 participants were randomised in the pilot trial, of whom 99 were allocated to the intervention and 101 were allocated to the control. We fully recruited early and achieved an 81% follow-up rate for our proposed primary outcome of the cumulative incidence of chlamydia at 12 months. There was no differential follow-up between groups. In total, 97% of messages sent were successfully delivered to participants' mobile phones. Recipients reported that the tone, language, content and frequency of messages were appropriate. Messages reportedly increased knowledge of and confidence in how to use condoms and negotiate condom use and reduced stigma about STIs, enabling participants to tell a partner about a STI. CONCLUSIONS: Our research shows that the intervention is acceptable and feasible to deliver. Our pilot trial demonstrated that a main trial is feasible. It remains unclear which behaviour change techniques and elements of the intervention or follow-up procedures are associated with effectiveness. A further limitation is that in the trial one person entering data and the participants were unmasked. A randomised controlled trial to establish the effects of the intervention on STIs at 12 months is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02304709. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 57. See the NIHR Journals Library website for further project information.

Effect of pre-exposure prophylaxis and combination HIV prevention for men who have sex with men in the UK: a mathematical modelling study.

BACKGROUND: HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection. METHODS: We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15-64 years) in the UK during 2014-20, including increasing rates of HIV testing, test-and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation. FINDINGS: We predicted a baseline of 16 955 new infections (IQR 13 156-21 669) in MSM in the UK during 2014-20. At a coverage of ≤50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61·8%, IQR 47·2-81·8, of total incidence) was greater than the sum of effects of the two interventions individually (32·6%, 23·7-46·0, and 23·9%, 16·5-33·3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587-9813) UK MSM from HIV infection (43·6%, IQR 32·9-57·9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely. INTERPRETATION: PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade. FUNDING: Health Protection Agency (now Public Health England).

Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM.

BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell count 350/µl. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. <535 new infections per year) by 2030, and whether this is likely to be cost-effective. METHODS: A dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. CONCLUSION: This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence.

The Men's Safer Sex (MenSS) trial: protocol for a pilot randomised controlled trial of an interactive digital intervention to increase condom use in men.

INTRODUCTION: Sexually transmitted infections (STI) are a major public health problem. Condoms provide effective protection but there are many barriers to use. Face-to-face health promotion interventions are resource-intensive and show mixed results. Interactive digital interventions may provide a suitable alternative, allowing private access to personally tailored behaviour change support. We have developed an interactive digital intervention (the Men's Safer Sex (MenSS) website) which aims to increase condom use in men. We describe the protocol for a pilot trial to assess the feasibility of a full-scale randomised controlled trial of the MenSS website in addition to usual sexual health clinical care. PARTICIPANTS: Men aged 16 or over who report female sexual partners and recent unprotected sex or suspected acute STI. PARTICIPANTS (N=166) will be enrolled using a tablet computer in clinic waiting rooms. All trial procedures will be online, that is, eligibility checks; study consent; trial registration; automated random allocation; and data submission. At baseline and at 3, 6 and 12 months, an online questionnaire will assess condom use, self-reported STI diagnoses, and mediators of condom use (eg, knowledge, intention). Reminders will be by email and mobile phone. The primary outcome is condom use, measured at 3 months. STI rates will be recorded from sexual health clinic medical records at 12 months. The feasibility of a cost-effectiveness analysis will be assessed, to calculate incremental cost per STI prevented (Chlamydia or Gonorrhoea), from the NHS perspective. ETHICS AND DISSEMINATION: Ethical approval: City and East NHS Research Ethics Committee (reference number 13 LO 1801). Findings will be made available through publication in peer-reviewed journals, and to participants and members of the public via Twitter and from the University College London eHealth Unit website. Raw data will be made available on request. TRIAL REGISTRATION NUMBER: Current Controlled Trials. ISRCTN18649610. Registered 15 October 2013 http://www.controlled-trials.com/ISRCTN18649610.

The Sexunzipped trial: optimizing the design of online randomized controlled trials.

BACKGROUND: Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions. Evaluations of digital interventions are increasingly conducted online. Trial administration and data collection online offers many advantages, but concerns remain over fraudulent registration to obtain compensation, the quality of self-reported data, and high attrition. OBJECTIVE: This study addresses the feasibility of several dimensions of online trial design-recruitment, online consent, participant identity verification, randomization and concealment of allocation, online data collection, data quality, and retention at 3-month follow-up. METHODS: Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the "Sexunzipped" online trial between November 2010 and March 2011 (n=2036). Participants filled in baseline demographic and sexual health questionnaires online and were randomized to the Sexunzipped interactive intervention website or to an information-only control website. Participants were also randomly allocated to a postal request (or no request) for a urine sample for genital chlamydia testing and receipt of a lower (£10/US$16) or higher (£20/US$32) value shopping voucher compensation for 3-month outcome data. RESULTS: The majority of the 2006 valid participants (90.98%, 1825/2006) were aged between 18 and 20 years at enrolment, from all four countries in the United Kingdom. Most were white (89.98%, 1805/2006), most were in school or training (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total, 3.88% (79/2036) of registrations appeared to be invalid and another 4.00% (81/2006) of participants gave inconsistent responses within the questionnaire. The higher value compensation (£20/US$32) increased response rates by 6-10%, boosting retention at 3 months to 77.2% (166/215) for submission of online self-reported sexual health outcomes and 47.4% (118/249) for return of chlamydia urine samples by post. CONCLUSIONS: It was quick and efficient to recruit young people to this online trial. Our procedures for obtaining online consent, verifying participant identity, automated randomization, and concealment of allocation worked well. The optimal response rate for the online sexual health outcome measurement was comparable to face-to-face trials. Multiple methods of participant contact, requesting online data only, and higher value compensation increased trial retention at 3-month follow-up. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 55651027; http://www.controlled-trials.com/ISRCTN55651027 (Archived by WebCite at http://www.webcitation.org/6LbkxdPKf).

Increased HIV testing and reduced undiagnosed infection among gay men in Scotland, 2005-8: support for the opt-out testing policy?

OBJECTIVE: To examine changes in HIV testing and undiagnosed infection among men who have sex with men in Scotland between 2005 and 2008. METHODS: Self-completed questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scene in Glasgow and Edinburgh. RESULTS: Questionnaires and oral fluid specimens were provided by 1350 men (51.6% response rate) in 2005 and 1277 (59.7% response rate) in 2008. 2572 men were eligible for inclusion in the analyses. Recent HIV testing increased from 33.2% in 2005 to 48.3% in 2008 (p<0.001). HIV prevalence was comparable in 2005 and 2008 (4.4% and 4.6%, respectively). Among HIV-positive men, there was a reduction in undiagnosed infection between 2005 and 2008 from 41.7% to 26.3% (p=0.08). Undiagnosed HIV did not differ between men who were and were not tested in the past year. In 2008, only four (26.7%) HIV-positive men tested in the past 6 months were undiagnosed, compared with 11 (42.3%) HIV-positive men who had not tested (p=0.03). CONCLUSION: There was a substantial increase in recent HIV testing between 2005 and 2008. Although there was a concurrent (non-significant) reduction in undiagnosed HIV, there was no difference in undiagnosed infection between men who had and had not tested recently. However, lower proportions of undiagnosed infection among the most recent HIV-positive testers suggest frequent testing could play a role in reducing undiagnosed HIV and should remain central to HIV prevention efforts.

Comparison of teenagers' early same-sex and heterosexual behavior: UK data from the SHARE and RIPPLE studies.

PURPOSE: North American research finds increased sexual risk-taking among teenagers with same-sex partners, but understanding of underlying processes is limited. The research carried out in the United Kingdom compares teenagers' early sexual experiences according to same- or opposite-sex partner, focusing on unwanted sex in addition to risk-taking, and exploring underlying psychosocial differences. METHODS: Multivariate analyses combined self-reported data from two randomized control trials of school sex education programs (N = 10,250). Outcomes from sexually experienced teenagers (N = 3,766) were partner pressure to have first sex and subsequent regret, and sexual risk measures including pregnancy. Covariates included self-esteem, future expectations, substance use, and communication with mother. RESULTS: By the time of follow-up (mean age, 16), same-sex genital contact (touching or oral or anal) was reported by 2.3% of teenagers, with the majority also reporting heterosexual intercourse. A total of 39% reported heterosexual intercourse and no same-sex genital contact. Boys were more likely to report partner pressure (Odds ratio [OR] = 2.56, 95% confidence intervals [CI] = 1.29-5.08) and regret (OR = 2.32; 95% CI = 1.39-3.86) in relation to first same-sex genital contact than first heterosexual intercourse, but girls showed no differences according to partner type. Teenagers with bisexual behavior reported greater pregnancy or partner pregnancy risk than teenagers with exclusively opposite-sex partners (girls, OR = 4.51, 95% CI = 2.35-8.64; boys, OR = 4.43, 95% CI = 2.41-8.14), partially reduced by attitudinal and behavioral differences. CONCLUSIONS: This UK study confirms greater reporting of sexual risk-taking among teenagers with same-sex partners, and suggests that boys in this group are vulnerable to unwanted sex. It suggests limitations to the interpretation of differences, in terms of psychosocial risk factors common to all adolescents.

HIV prevention while the bulldozers roll: exploring the effect of the demolition of Goa's red-light area.

Interventions targeting sex-workers are pivotal to HIV prevention in India. Community mobilisation is considered by the National AIDS Control Programme to be an integral component of this strategy. Nevertheless societal factors, and specifically policy and legislation around sex-work, are potential barriers to widespread collectivisation and empowerment of sex-workers. Between November 2003 and December 2005 we conducted participatory observation and rapid ethnographic mapping with several hundred brief informant interviews, in addition to 34 semi-structured interviews with key-informants, 16 in-depth interviews with female sex-workers, and 3 focus-group-discussions with clients and mediators. This provides a detailed examination of the demolition of Baina, one of India's large red-light areas, in 2004, and one of the first accounts of the effect of dismantling the red-light area on the organisation of sex-work and sex-workers' sexual risk. The results suggest that the concentrated and homogeneous brothel-based sex-work environment rapidly evolved into heterogeneous, clandestine and dispersed modes of operation. The social context of sex-work that emerged from the dust of the demolition was higher risk and less conducive to HIV prevention. The demolition acted as a negative structural intervention; a catastrophic event that fragmented sex-workers' collective identity and agency and rendered them voiceless and marginalised. The findings suggest that an abolitionist approach to sex-work and legislation or policy that either criminalises this large group of women, or renders them as invisible victims, will increase the stigma and exclusion they experience. For the targeted HIV prevention approaches advocated by the National AIDS Control Programme to be effective, there is a need for legislation and policy that supports sex-workers' agency and self-organisation and enables them to create a safer working environment for themselves.

Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours.

BACKGROUND: Systematic reviews based on the critical appraisal of observational and analytic studies on HIV prevalence and risk factors for HIV transmission among men having sex with men are very useful for health care decisions and planning. Such appraisal is particularly difficult, however, as the quality assessment tools available for use with observational and analytic studies are poorly established. METHODS: We reviewed the existing quality assessment tools for systematic reviews of observational studies and developed a concise quality assessment checklist to help standardise decisions regarding the quality of studies, with careful consideration of issues such as external and internal validity. RESULTS: A pilot version of the checklist was developed based on epidemiological principles, reviews of study designs, and existing checklists for the assessment of observational studies. The Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO) Score consists of five items: External validity (1 item), reporting (2 items), bias (1 item) and confounding factors (1 item). Expert opinions were sought and it was tested on manuscripts that fulfil the inclusion criteria of a systematic review. Like all assessment scales, QATSO may oversimplify and generalise information yet it is inclusive, simple and practical to use, and allows comparability between papers. CONCLUSION: A specific tool that allows researchers to appraise and guide study quality of observational studies is developed and can be modified for similar studies in the future.

Social, behavioural, and intervention research among people of Sub-Saharan African origin living with HIV in the UK and Europe: literature review and recommendations for intervention.

Africans are the second largest group affected by HIV in Western Europe after men who have sex with men (MSM). This review describes and summarises the literature on social, behavioural, and intervention research among African communities affected by HIV in the UK and other European countries in order to make recommendations for future interventions. We conducted a keyword search using Embase, Medline and PsychInfo, existing reviews, 'grey literature', as well as expert working group reports. A total of 138 studies met our inclusion criteria; 31 were published in peer-reviewed journals, 107 in the grey literature. All peer-reviewed studies were observational or "descriptive," and none of them described HIV interventions with African communities. However, details of 36 interventions were obtained from the grey literature. The review explores six prominent themes in the descriptive literature: (1) HIV testing; (2) sexual lifestyles and attitudes; (3) gender; (4) use of HIV services; (5) stigma and disclosure (6) immigration status, unemployment and poverty. Although some UK and European interventions are addressing the needs of African communities affected by HIV, more resources need to be mobilised to ensure current and future interventions are targeted, sustainable, and rigorously evaluated.

After the euphoria: HIV medical technologies from the perspective of their prescribers.

This paper focuses on the relationship of HIV medical technologies to current styles of medical practice and highlights issues posed by the technologies for those working and/or living with HIV. The paper examines HIV anti-retroviral combination therapies and associated tests from the perspective of their prescribers. The prescribers were interviewed during the later part of 2002 at three London HIV clinics. Their comments, considered in light of other recent studies in the field, suggest that current therapies are part of a transitional phase in the epidemic which informs the identification and negotiation of known risks and uncertainty. An undetermined but extended life expectancy, afforded by anti-retroviral therapies, is understood against risk of iatrogenic diseases and/or viral drug resistance. The tension arising in this situation of unwanted and even uncertain phenomena poses ethical dilemmas and affects doctor/patient relations. Indeed, it also contributes to a reconfiguring of the lived experience of managing HIV. While the new technologies have offered considerable advances in the medical management of HIV, they are altering the nature of HIV medicine both materially and socially. The scenario is further complicated by the uneven allocation of resources and different patient health and disease states. The heterogeneity of resources, disease states and technological effects points to the need for ongoing and extended evaluation as the relationship between these and the everyday practice of medicine continues to change.

Heterosexual risk behaviour among young teenagers in Scotland.

This paper provides the first detailed data on the heterosexual sexual experience of a large sample of 14-year-olds in Scotland. The paper investigates the prevalence, nature and correlates of early heterosexual intercourse, and the extent and correlates of condom use. Questionnaires were administered in 24 schools under examination conditions (N=7630). Eighteen per cent of boys and 15% of girls reported having had intercourse. Sixty per cent reported condoms were "used throughout". The most important correlate of sexual experience was low level of parental monitoring; the key predictor for condom use was whether or not the respondent talked to their partner about protection before having sexual intercourse.