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

INTRODUCTION: HIV 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. METHODS: We 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. RESULTS: Barriers 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. CONCLUSIONS: PrEP 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.

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 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. 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.

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.

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.

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.

Population-level effectiveness of a national HIV preexposure prophylaxis programme in MSM.

OBJECTIVE: The aim of this study was to evaluate Scotland's national HIV preexposure prophylaxis (PrEP) programme in relation to PrEP uptake and associated population-level impact on HIV incidence among MSM. DESIGN: A retrospective cohort study within real-world implementation. METHODS: Comparison of HIV diagnoses from national surveillance data and HIV incidence within a retrospective cohort of HIV-negative MSM attending sexual health clinics from the National Sexual Health information system between the 2-year periods pre(July 2015-June 2017) and post(July 2017-June 2019) introduction of PrEP. RESULTS: Of 16 723 MSM attending sexual health services in the PrEP period, 3256 (19.5%) were prescribed PrEP. Between pre-PrEP and PrEP periods, new HIV diagnoses among MSM declined from 229 to 184, respectively [relative risk reduction (RRR): 19.7%, 95% confidence interval (95% CI) 2.5-33.8]; diagnosed recently acquired infections declined from an estimated 73 to 47, respectively (35.6%, 95% CI 7.1-55.4). Among MSM attending sexual health clinics, HIV incidence per 1000 person-years declined from 5.13 (95% CI 3.90-6.64) pre-PrEP to 3.25 (95% CI 2.30-4.47) in the PrEP period (adjusted IRR 0.57, 95% CI 0.37-0.87). Compared with the pre-PrEP period, incidence of HIV was lower in the PrEP period for those prescribed PrEP (aIRR 0.25, 95% CI 0.09-0.70) and for those not prescribed PrEP (aIRR 0.68, 95% CI 0.43-1.05). CONCLUSION: We demonstrate national population-level impact of PrEP for the first time in a real-world setting. HIV incidence reduced in MSM who had been prescribed PrEP and, to a lesser extent, in those who had not. Promotion of the benefits of PrEP needs to extend to MSM who do not access sexual health clinics.

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. TRIAL REGISTRATION NUMBER: ISRCTN15996256.

What impact has tendering had on trainees? Results of a national survey by British Association for Sexual Health and HIV Trainees' Collaborative for audit, research and quality improvement projects.

In April 2013, local authorities gained responsibility for commissioning sexual health services in England. With many services going out to tender and resultant change in services or service provider, there is anecdotal evidence that this has impacted on the education, training and morale of genitourinary medicine (GUM) trainees. The aim of this study was to evaluate the impact of tendering on GUM trainees. An electronic survey designed by the British Association for Sexual Health and HIV Trainees' Collaborative for Audit, Research and Quality Improvement Projects (T-CARQ) was distributed to GUM trainees and newly appointed consultants. Eighty-two individuals responded (74% GUM trainees, 25% newly appointed consultants, 1% locum appointed for service). Sixty-three per cent (45/72) had experience of training within a service which was being tendered. Of these, 59% (24/41) felt their training was not considered during the tendering process and 20% (8/41) felt that it was. Forty-four per cent (18/41) felt adequately supported. Thirty per cent (12/40) reported active participation in the tendering process. On a scale of 0 (no impact) to 5 (major impact), the median score for impact of tendering on training was 2. The positive/negative impact of tendering on different training elements was rated: other than management experience the overall impact on all parameters was negative, namely morale, senior support and education. In conclusion, this survey describes the variable impact of service tendering on GUM training. Our recommendations for maintaining training standards despite tendering include actively involving trainees and education partners, inclusion of specialist GUM training in service specifications, development of guidance for commissioners and services for the management of GUM training within tendering.

Don't ask, sometimes tell. A survey of men who have sex with men sexual orientation disclosure in general practice.

Despite advances in lesbian, gay, bisexual and transgender equality in recent years, some men who have sex with men remain at increased risk of ill-health. Positive interventions in primary care include psychological support and strategies for risk reduction. It is important that men who have sex with men can disclose sexual orientation in primary care. To quantify disclosure of sexual orientation by men who have sex with men attending general practice and identify barriers to disclosure we surveyed a group of Scottish men. A questionnaire was distributed by voluntary organisations and the National Health Service in the West of Scotland, to rural and urban populations. Two hundred and four gave evaluable responses, with all ages represented. A total of 199 (98%) were registered with a General Practitioner and 167 (83%) attended in the previous year. A total of 81 (40%) stated staff were aware of their sexual orientation. A total of 93/121 (75%) men who have sex with men whose GP was unaware stated this was because they had never been asked. A total of 36/81(44%) men who have sex with men rated support from practices since disclosure as 'excellent' and qualitative responses were positive. It is reassuring that almost all respondents were registered with GPs and attending primary care services. However, only 40% had disclosed sexual orientation. This was not because of fear of negative impact on care but because men who have sex with men felt it was irrelevant to their attendance. GPs appear to be reluctant to raise the issue of sexual orientation without prompting.

Urine testing as a surveillance tool to monitor the impact of HPV immunization programs.

HPV surveillance is necessary to monitor the impact and success of HPV immunization programs. This study was designed to evaluate the performance of HPV testing in urine to assess its suitability for epidemiological and surveillance purposes. A total of 90 females and 117 males were recruited from a UK drop-in clinic offering integrated sexual health services. A urine sample and comparator gold-standard sample (cervical liquid-based cytology sample or penile swab) was collected from each subject. HPV detection was performed using a PCR-based assay. Discrepancy between the two overall distributions [urine vs. gold standard (GS)] was measured. At the individual level, sensitivity and specificity of HPV detection in urine versus GS was measured. Prevalence of HPV was higher in urine compared to GS in both females and males. At the individual level, sensitivity of urine versus GS for HPV detection was 90.5% (79.3-96.9) and 55.9% (37.8-72.8) in females and males, respectively. The overall distribution of HPV types in urine was similar to that in gold standard, (P = 0.78; male, P = 0.88; female). Type-specific matches in urine versus GS were achieved in 71% (61-79.5) and 63.2% (54.2-71.4) of samples from females and males, respectively. Urine, particularly from females, is a useful biospecimen for HPV surveillance purposes. Further examination into the usefulness of urine from males, including choice of relevant gold-standard comparator, is required.

Clinical standards for the screening and management of acquired syphilis in HIV-positive adults.

These clinical standards for the screening and management of acquired syphilis in HIV-positive patients in the UK were first made available on the MSSVD website in February 2002. They have been updated by the 2006 UK National Guideline on the Sexual Health of People with HIV which is also published in this issue of the Journal [pp. 594-606]. Many of the recommendations remain in force and therefore the original document is published in full here.

A comparative study of clinical management strategies for vaginal discharge in family planning and genitourinary medicine settings.

OBJECTIVE: To compare strategies for management of women with vaginal discharge in genitourinary medicine (GUM) and family planning (FP) settings. METHODS: The setting was a centre housing both FP and GUM departments within a primary care trust in Scotland. The study participants were 200 women presenting with vaginal discharge. A randomised, controlled, crossover design was employed. Strategies typical of FP and GUM were performed on every participant in a randomised sequence. Day 1 diagnoses were made by the FP strategy (history and examination) and the GUM strategy (nearpatient microscopy added). Day 7 results were obtained from final analysis of all specimens. Days 1 and 7 results were compared with the reference standard provided by all the test results. The main outcome measures were incorrect diagnoses on Days 1 and 7. RESULTS: On Day 1 the FP strategy resulted in significantly more incorrect diagnoses than the GUM strategy when compared with the reference standard (73 vs 32; p <0.001). On Day 7 the GUM strategy resulted in significantly more incorrect diagnoses than the FP strategy when compared with the reference standard (32 vs 17; p = 0.019). CONCLUSIONS: Vaginal discharge can be managed effectively in community settings such as FP and primary care. The addition of near-patient microscopy produces a more accurate immediate diagnosis. The addition of a high vaginal swab for culture produces a more accurate final diagnosis. The costs of on-site microscopy must be considered.

Client perspectives on sexual health service provision.

Development of integrated genitourinary medicine (GUM) and family planning (FP) services must take into account the views and requirements of service users. As we strive to modernize sexual health services, various changes are being introduced, such as a policy of no microscopy for selected patients attending GUM clinics. In order to determine the views of our clients prior to implementation of change, we performed a qualitative study in our UK centre, which houses both FP and GUM. One hundred women presenting to FP and 100 to GUM were interviewed. In addition, we collected details of their characteristics to identify any significant differences in users attending each clinic. A summary of their views and characteristics is presented. Although near-patient testing results in a longer time spent in clinic, 99% of participants expressed a preference for immediate microscopy results and treatment. GUM and FP clients exhibited many similar characteristics.

Medical management of sexual difficulties in HIV-positive individuals.

In the current era of effective antiretroviral therapy, sexual dysfunction is being increasingly recognized in HIV-positive individuals. This article reviews the literature about the causes, treatments available and any issues specific to the HIV-positive individual.