Implementation of a national HIV pre-exposure prophylaxis service is associated with changes in characteristics of people with newly diagnosed HIV: a retrospective cohort study

OBJECTIVES: To review characteristics of individuals newly diagnosed with HIV following implementation of a national pre-exposure prophylaxis (PrEP) programme (comprehensive PrEP services, delivered in sexual health clinics) to inform future delivery and broader HIV prevention strategies. METHODS: We extracted data from national HIV databases (July 2015–June 2018). We compared sociodemographic characteristics of individuals diagnosed in the period before and after PrEP implementation, and determined the proportion of ‘potentially preventable’ infections with the sexual health clinic–based PrEP delivery model used. RESULTS: Those diagnosed with HIV before PrEP implementation were more likely to be male (342/418, 81.8% vs 142/197, 72.1%, p=0.005), be white indigenous (327/418, 78.2% vs 126/197, 64.0%, p<0.001), report transmission route as sex between men (219/418, 52.4% vs 81/197, 41.1%, p=0.014), and have acquired HIV in the country of the programme (302/418, 72.2% vs 114/197, 57.9% p<0.001) and less likely to report transmission through heterosexual sex (114/418, 27.3% vs 77/197, 39.1%, p=0.002) than after implementation. Pre-implementation, 8.6% (36/418) diagnoses were ‘potentially preventable’ with the PrEP model used. Post-implementation, this was 6.6% (13/197), but higher among those with recently acquired HIV (49/170, 28.8%). Overall, individuals with ‘potentially preventable’ infections were more likely to be male (49/49, 100% vs 435/566, 76.9%, p<0.001), aged <40 years (37/49, 75.5% vs 307/566, 54.2%, p=0.004), report transmission route as sex between men (49/49, 100% vs 251/566, 44.3%, p<0.001), have previously received post-exposure prophylaxis (12/49, 24.5% vs 7/566, 1.2%, p<0.001) and less likely to be black African (0/49, 0% vs 67/566, 11.8%, p=0.010) than those not meeting this definition. CONCLUSIONS: The sexual health clinic–based national PrEP delivery model appeared to best suit men who have sex with men and white indigenous individuals but had limited reach into other key vulnerable groups. Enhanced models of delivery and HIV combination prevention are required to widen access to individuals not benefiting from PrEP at present

Improving HIV Pre Exposure Prophylaxis (PrEP) uptake and initiation: process evaluation and recommendation development from a national PrEP programme

HIV pre-exposure prophylaxis (PrEP) is key to HIV transmission elimination but implementation is challenging and under-researched. We undertook a process evaluation of the first 2years of a national PrEP program to explore barriers and facilitators to implementation and to develop recommendations to improve implementation, focusing on PrEP uptake and initiation. Stage 1 involved semi-structured telephone interviews and focus groups (September 2018-July 2019) with geographically and demographically diverse patients seeking/using/declining/stopping PrEP (n =39), sexual healthcare professionals (n =54), community-based organisation service users (n =9) and staff (n =15) across Scotland. We used deductive thematic analysis, to derive and then map key barriers and facilitators to priority areas that experts agreed would enhance uptake and initiation. In Stage 2, we used analytic tools from implementation science to systematically generate evidence-based, theoretically-informed recommendations to enhance uptake and initiation of PrEP. Barriers and facilitators were multi-levelled and interdependent. Barriers included the rapid pace of implementation without additional resource, and a lack of familiarity with PrEP prescribing. Facilitators included opportunities for acquisition of practice-based knowledge and normalisation of initiation activities. We refined our 68 'long-list' recommendations to 41 using expert input and the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria. Examples include: provision of PrEP in diverse settings to reach all in need; co-produced, culturally sensitive training resources for healthcare professionals, with focused content on non-daily dosing; meaningful collaborative working across all stakeholders. These evidence-based, theory informed recommendations provide a robust framework for optimising PrEP uptake and initiation in diverse settings to ensure PrEP reaches all who may benefit

Improving HIV pre-exposure prophylaxis (PrEP) uptake and initiation: process evaluation and recommendation development from a national PrEP program

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is key to HIV transmission elimination but implementation is challenging and under-researched. We undertook a process evaluation of the first 2 years of a national PrEP program to explore barriers and facilitators to implementation and to develop recommendations to improve implementation, focusing on PrEP uptake and initiation. METHODS: Stage 1 involved semi-structured telephone interviews and focus groups (September 2018–July 2019) with geographically and demographically diverse patients seeking/using/declining/stopping PrEP (n = 39), sexual healthcare professionals (n = 54), community-based organisation service users (n = 9) and staff (n = 15) across Scotland. We used deductive thematic analysis, to derive and then map key barriers and facilitators to priority areas that experts agreed would enhance uptake and initiation. In Stage 2, we used analytic tools from implementation science to systematically generate evidence-based, theoretically-informed recommendations to enhance uptake and initiation of PrEP. RESULTS: Barriers and facilitators were multi-levelled and interdependent. Barriers included the rapid pace of implementation without additional resource, and a lack of familiarity with PrEP prescribing. Facilitators included opportunities for acquisition of practice-based knowledge and normalisation of initiation activities. We refined our 68 ‘long-list’ recommendations to 41 using expert input and the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria. Examples include: provision of PrEP in diverse settings to reach all in need; co-produced, culturally sensitive training resources for healthcare professionals, with focused content on non-daily dosing; meaningful collaborative working across all stakeholders. CONCLUSIONS: These evidence-based, theory informed recommendations provide a robust framework for optimising PrEP uptake and initiation in diverse settings to ensure PrEP reaches all who may benefit

Going beyond ‘regular and casual’: development of a classification of sexual partner types to enhance partner notification for STIs

OBJECTIVES To develop a classification of sexual partner types for use in partner notification (PN) for STIs. METHODS A four-step process: (1) an iterative synthesis of five sources of evidence: scoping review of social and health sciences literature on partner types; analysis of relationship types in dating apps; systematic review of PN intervention content; and review of PN guidelines; qualitative interviews with public, patients and health professionals to generate an initial comprehensive classification; (2) multidisciplinary clinical expert consultation to revise the classification; (3) piloting of the revised classification in sexual health clinics during a randomised controlled trial of PN; (4) application of the Theoretical Domains Framework (TDF) to identify index patients' willingness to engage in PN for each partner type. RESULTS Five main partner types emerged from the evidence synthesis and consultation: 'established partner', 'new partner', 'occasional partner', 'one-off partner' and 'sex worker'. The types differed across several dimensions, including likely perceptions of sexual exclusivity, likelihood of sex reoccurring between index patient and sex partner. Sexual health professionals found the classification easy to operationalise. During the trial, they assigned all 3288 partners described by 2223 index patients to a category. The TDF analysis suggested that the partner types might be associated with different risks of STI reinfection, onward transmission and index patients' engagement with PN. CONCLUSIONS We developed an evidence-informed, useable classification of five sexual partner types to underpin PN practice and other STI prevention interventions. Analysis of biomedical, psychological and social factors that distinguish different partner types shows how each could warrant a tailored PN approach. This classification could facilitate the use of partner-centred outcomes. Additional studies are needed to determine the utility of the classification to improve measurement of the impact of PN strategies and help focus resources

Accelerated partner therapy contact tracing for people with chlamydia (LUSTRUM): a crossover cluster-randomised controlled trial.

BACKGROUND Accelerated partner therapy has shown promise in improving contact tracing. We aimed to evaluate the effectiveness of accelerated partner therapy in addition to usual contact tracing compared with usual practice alone in heterosexual people with chlamydia, using a biological primary outcome measure. METHODS We did a crossover cluster-randomised controlled trial in 17 sexual health clinics (clusters) across England and Scotland. Participants were heterosexual people aged 16 years or older with a positive Chlamydia trachomatis test result, or a clinical diagnosis of conditions for which presumptive chlamydia treatment and contact tracing are initially provided, and their sexual partners. We allocated phase order for clinics through random permutation within strata. In the control phase, participants received usual care (health-care professional advised the index patient to tell their sexual partner[s] to attend clinic for sexually transmitted infection screening and treatment). In the intervention phase, participants received usual care plus an offer of accelerated partner therapy (health-care professional assessed sexual partner[s] by telephone, then sent or gave the index patient antibiotics and sexually transmitted infection self-sampling kits for their sexual partner[s]). Each phase lasted 6 months, with a 2-week washout at crossover. The primary outcome was the proportion of index patients with a positive C trachomatis test result at 12-24 weeks after contact tracing consultation. Secondary outcomes included proportions and types of sexual partners treated. Analysis was done by intention-to-treat, fitting random effects logistic regression models. This trial is registered with the ISRCTN registry, 15996256. FINDINGS Between Oct 24, 2018, and Nov 17, 2019, 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. All clinics completed both phases. In total, 4807 sexual partners were reported, of whom 1636 (34%) were steady established partners. Overall, 293 (19%) of 1536 index patients chose accelerated partner therapy for a total of 305 partners, of whom 248 (81%) accepted. 666 (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for C trachomatis at 12-24 weeks after contact tracing consultation; 31 (4·7%) in the intervention phase and 53 (6·6%) in the control phase had a positive C trachomatis test result (adjusted odds ratio [OR] 0·66 [95% CI 0·41 to 1·04]; p=0·071; marginal absolute difference -2·2% [95% CI -4·7 to 0·3]). Among index patients with treatment status recorded, 775 (88·0%) of 881 patients in the intervention phase and 760 (84·6%) of 898 in the control phase had at least one treated sexual partner at 2-4 weeks after contact tracing consultation (adjusted OR 1·27 [95% CI 0·96 to 1·68]; p=0·10; marginal absolute difference 2·7% [95% CI -0·5 to 6·0]). No clinically significant harms were reported. INTERPRETATION Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving. Future research should find ways to increase uptake of accelerated partner therapy and develop alternative interventions for one-off sexual partners. FUNDING National Institute for Health Research

Accelerated partner therapy (APT) partner notification for people with Chlamydia trachomatis: protocol for the Limiting Undetected Sexually Transmitted infections to RedUce Morbidity (LUSTRUM) APT cross-over cluster randomised controlled trial

Introduction: Partner notification (PN) is a process aiming to identify, test and treat the sex partners of people (index patients) with sexually transmitted infections (STIs). Accelerated partner therapy (APT) is a PN method whereby healthcare professionals assess sex partners, by telephone consultation, before giving the index patient antibiotics and STI self-sampling kits to deliver to their sex partner(s). The Limiting Undetected Sexually Transmitted infections to RedUce Morbidity programme aims to determine the effectiveness of APT in heterosexual women and men with chlamydia and determine whether APT could affect Chlamydia trachomatis transmission at population level. Methods and analysis: This protocol describes a cross-over cluster randomised controlled trial of APT, offered as an additional PN method, compared with standard PN. The trial is accompanied by an economic evaluation, transmission dynamic modelling and a qualitative process evaluation involving patients, partners and healthcare professionals. Clusters are 17 sexual health clinics in areas of England and Scotland with contrasting patient demographics. We will recruit 5440 heterosexual women and men with chlamydia, aged ≥16 years. The primary outcome is the proportion of index patients testing positive for C. trachomatis 12-16 weeks after the PN consultation. Secondary outcomes include: proportion of sex partners treated; cost effectiveness; model-predicted chlamydia prevalence; experiences of APT. The primary outcome analysis will be by intention-to-treat, fitting random effects logistic regression models that account for clustering of index patients within clinics and trial periods. The transmission dynamic model will be used to predict change in chlamydia prevalence following APT. The economic evaluation will use mathematical modelling outputs, taking a health service perspective. Qualitative data will be analysed using interpretative phenomenological analysis and framework analysis. Ethics and dissemination: This protocol received ethical approval from London—Chelsea Research Ethics Committee (18/LO/0773). Findings will be published with open access licences

Improving sexual health through partner notification : the LUSTRUM mixed-methods research Programme including RCT of accelerated partner therapy

Background Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission develop and cost partner notification interventions for men who have sex with men. Design Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings Sexual health clinics and community services in England and Scotland. Participants Women and men, including men who have sex with men and people with mild learning disabilities. Interventions Accelerated partner therapy offered as an additional partner notification method. Main outcome measures Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system. In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixty-six (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of gonorrhoea and human immunodeficiency virus co-infection in men who have sex with men was technically challenging. Limitations In the randomised controlled trial, enrolment, follow-up and repeat infections were lower than expected, so statistical power was lower than anticipated. We were unable to determine whether accelerated partner therapy sped up partner treatment. Mathematical modelling of gonorrhoea/human immunodeficiency virus co-infection in men who have sex with men remained at an experimental stage. It was not feasible to include healthcare professionals in the men who have sex with men intervention development due to the COVID-19 pandemic. Conclusions Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving, but is best suited to sex partners with emotional connection to the index patient. The Programme’s findings about classification of sexual partner types can be implemented in sexual health care with auditable outcomes. Future work Further research is needed on how to increase uptake of accelerated partner therapy and increase sexually transmitted infections self-sampling by partners; understand how services can use partnership-type information to improve partner notification, especially for those currently underserved; overcome challenges in modelling sexually transmitted infections and human immunodeficiency virus co-infection in men who have sex with men; develop and evaluate an intervention to optimise partner notification among men who have sex with men, focusing on one-off partnerships. Trial registration This trial is registered as ISRCTN15996256. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0614-20009) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information

Improving HIV pre-exposure prophylaxis (PrEP) adherence and retention in care: Process evaluation and recommendation development from a nationally implemented PrEP programme.

IntroductionHIV pre-exposure prophylaxis (PrEP), in which people take HIV medication to prevent HIV acquisition, underpins global HIV transmission elimination strategies. Effective prevention needs people to adhere to PrEP and remain in care during periods of risk, but this is difficult to achieve. We undertook a process evaluation of Scotland's PrEP programme to explore barriers and facilitators to PrEP adherence and retention in care and to systematically develop evidence-based, theoretically-informed recommendations to address them.MethodsWe conducted semi-structured interviews and focus groups (09/2018-07/2019) with patients who identified as gay or bisexual men and were either using PrEP, had declined the offer of PrEP, had stopped PrEP, or had been assessed as ineligible for PrEP (n = 39 of whom n = 5 (13%) identified as trans, median age 31 years and interquartile range 14 years), healthcare professionals involved in PrEP provision (n = 54 including specialist sexual health doctors and nurses of various grades, PrEP prescribing general practitioners, health promotion officers, midwifes, and a PrEP clinical secretary), and clients (n = 9) and staff (n = 15) of non-governmental organisations with an HIV prevention remit across Scotland. We used thematic analysis to map key barriers and facilitators to priority areas that could enhance adherence and retention in care. We used implementation science analytic tools (Theoretical Domains Framework, Intervention Functions, Behaviour Change Technique Taxonomy, APEASE criteria) and expert opinion to systematically generate recommendations.ResultsBarriers included perceived complexity of on-demand dosing, tendency for users to stop PrEP before seeking professional support, troublesome side-effects, limited flexibility in the settings/timings/nature of review appointments, PrEP-related stigma and emerging stigmas around not using PrEP. Facilitators included flexible appointment scheduling, reminders, and processes to follow up non-attenders. Examples of the 25 recommendations include: emphasising benefits of PrEP reviews and providing appointments flexibly within individualised PrEP care; using clinic systems to remind/recall PrEP users; supporting PrEP conversations among sexual partners; clear on-demand dosing guidance; encouraging good PrEP citizenship; detailed discussion on managing side-effects and care/coping planning activities.ConclusionsPrEP adherence and retention in care is challenging, reducing the effectiveness of PrEP at individual and population levels. We identify and provide solutions to where and how collaborative interventions across public health, clinical, and community practice could address these challenges