PrEP-LANA (Pre-exposure Prophylaxis- Long-acting Novel Antiviral Agent)

PrEP-LANA (Pre-exposure Prophylaxis- Long-acting Novel Antiviral Agent)

The goal of this 12-month implementation science study is to generate the evidence required to ensure long-acting cabotegravir (LA CAB) as pre-exposure prophylaxis (PrEP) can be delivered in an equitable manner within the NHS. This study will recruit both PrEP users and healthcare professionals (HCPs).

The main questions it aims to answer are:

• What do healthcare providers think about the feasibility of delivering LA CAB PrEP within sexual health services in the NHS?
• How many participants stay on/remain consistent with LA CAB PrEP injections at Month 12 (PrEP persistence)?

Participants (200 PrEP users) will be followed for 12-months and asked to complete surveys at 3 study visits. A subset of 20 participants will also be asked to complete interviews about their experiences. We will also ask 20 HCPs at participating locations to complete surveys and interviews at both baseline and month 12.

A core principle of equity (understanding any difference in impact on underserved populations) will be applied throughout the study. To ensure representation of a diverse group of participants that reflects the demographic groups most affected by incident HIV and most underserved by PrEP in the UK, enrolment targets will be applied and meticulously managed by the central study team, as follows:

• A cap of 30% (n=60) will be applied to recruitment of White cisgender men who have sex with men who are not otherwise part of other under-represented groups (as defined below),
• At least 70%% (n=140) of participants will represent groups currently underserved by PrEP and fall into one (or more) of the following socio-demographic categories: women (defined cisgender or transgender) OR as transgender men OR non-binary individuals OR age<25 yrs, OR sex workers OR people who inject drugs OR racially minoritised heterosexual men.

Background

The introduction of pre-exposure prophylaxis (PrEP) marked a major scientific advance in HIV prevention. However, its public health value depends on whether individuals at risk feel able to access it and remain protected over time. In the UK, this is not currently realised equally across population groups. The UK Health Security Agency reported that in 2024, PrEP initiation or continuation among people with a PrEP need was 79.4% in White gay and bisexual men and 77.8% in ethnic minority gay and bisexual men, but much lower in Black African heterosexual women (34.6%), Black African heterosexual men (36.4%), and other ethnic minority heterosexual adults (43.9%). (1) PrEP delivery approaches are yet to address these inequities.

Daily oral tenofovir-based PrEP (TDF/FTC) remains the standard PrEP option in the UK. (2) However, its effectiveness depends on consistent use over time. This is often not achieved in practice. For example, a meta-analysis of 59 longitudinal studies involving 43,917 participants initiating oral PrEP globally found that 41.0% discontinued within 6 months and 37.7% had suboptimal adherence over the same period. (3) It has been suggested since 2018 that adherence to oral PrEP is particularly challenging for cisgender women and younger people. (4) This is supported by recent trial data. In HPTN 082, a randomised study of daily oral PrEP among adolescent girls and young women in South Africa and Zimbabwe, 95% initiated oral PrEP, but only 21% had drug levels consistent with high adherence at month 6, with this number dropping to 9% at month 12. (5) In HPTN 084, a phase 3 randomised trial conducted at 20 sites across seven sub-Saharan African countries among cisgender women, adherence was similarly low, with only 42.1% of plasma samples in a random subset consistent with daily use. (6) Daily oral dosing is also recognised as harder to sustain for individuals who struggle with oral medicines or regular engagement with services, and those experiencing homelessness, unstable housing, or intimate partner violence. (7) Taken together, these findings suggest that service models built primarily around daily oral PrEP leave some populations with less protection against HIV acquisition.

Long-acting injectable cabotegravir (LA CAB) offers an alternative PrEP modality. (7) On 5 November 2025, NICE recommended LA CAB for preventing HIV-1 in adults and young people at high risk of sexually acquired HIV-1 infection who cannot have oral PrEP. (7) This includes people for whom oral PrEP is medically contraindicated, people who cannot take tablets, and people for whom oral PrEP is unsuitable because of social or personal circumstances. (7) Superior efficacy of LA CAB compared with daily oral TDF/FTC has been demonstrated in two large, randomised trials. HPTN 083, conducted across sites in the United States, Latin America, Asia and Africa among cisgender men and transgender women who have sex with men, found that LA CAB was superior to daily oral TDF/FTC for HIV prevention. (8) In the blinded phase of HPTN 083, 91.5% of person-years were covered by on-time injections. (8) In the oral TDF/FTC arm, 74.2% of participants had plasma tenofovir concentrations consistent with daily dosing. (9) HPTN 084, conducted in sub-Saharan Africa among cisgender women, found HIV incidence of 0.20 versus 1.85 per 100 person-years, corresponding to an 88% lower risk of HIV acquisition with cabotegravir. (6) Injection coverage in HPTN 084 reached 93% of person-years, whereas 42.1% of plasma samples in a random subset of the oral TDF/FTC group were consistent with daily use. (6) These trials establish LA CAB as a more efficacious PrEP option than daily oral TDF/FTC in the populations studied. Furthermore, data modelling the impact of rapid LAI PrEP scale up in men who have sex with men in the Netherlands, demonstrated that offering individuals LAI PrEP had the potential to avert between 14-21% of new infections within 10 years of introduction. (10) US modelling estimates similarly suggest that LAI PrEP could reduce HIV incidence by 4%-36% over a 10-year period. (11,12) Early implementation data suggest that LA CAB can be delivered effectively, acceptably, and feasibly in routine practice, but the evidence base remains limited. In a two-clinic Italian implementation report, LA CAB was offered to 265 people prioritised because of barriers to oral PrEP, with injection adherence (defined as injections within a 7-day window) exceeding 95%, favourable tolerability, and only 1.5% discontinuing because of drug-related reasons. (13) In another Italian study, a prospective real-world cohort from Milan, LA CAB PrEP was associated with high acceptability and improved perceived adherence, convenience and HIV protection, although the cohort was almost exclusively cisgender men who have sex with men and most participants had prior oral PrEP experience. (14) In the Trio Health cohort in the United States, no incident HIV diagnoses were identified among 526 LA CAB PrEP users, and reported persistence was 92% at 6 months and 85% at 12 months. (15) However, these persistence estimates remain uncertain, due to limitations in follow-up and overlap in how adherence and persistence were defined. (7) Interim patient findings from the EBONI study among Black cisgender and transgender women in the United States likewise suggest high acceptability and feasibility, while interim healthcare provider findings indicate that delivery depends on staff preparation, workable local pathways, and reminder or tracking systems. (16,17) Formative implementation work from ImPrEP CAB Brazil similarly identified the need for service-delivery optimisation, including visit duration, staff training, support for injection appointments, and the value of educational and reminder tools. (18)

5.2. Rationale

With efficacy established, the central question is how cabotegravir PrEP should be implemented in routine UK care. In its 2025 appraisal, NICE highlighted uncertainty around the population likely to receive cabotegravir in practice, expected engagement with sexual health services among underserved groups, rates of transition between cabotegravir and oral PrEP, and whether any improvement in persistence would be realised in routine care. (7) These uncertainties have important policy and practice implications in the UK, due to existing PrEP pathways remaining inequitably distributed. (1,7) As LA CAB uptake begins in the UK, what remains unclear is how cabotegravir PrEP will be accessed, delivered, used over time, interrupted, or switched within NHS pathways, and whether its potential advantages will translate into more consistent protection for groups whose needs are not well met by current oral PrEP provision. It is also uncertain what implementation strategies could optimise this adoption and ongoing use. A UK-based implementation study is therefore needed to examine uptake, engagement, persistence, modality switching, and continuity of PrEP coverage under routine conditions, and in the context of various implementation strategies.

This study is also grounded in emerging UK implementation work. There have already been a small number of oral PrEP pilot projects in the UK exploring delivery outside specialist sexual health services, including a community pharmacy awareness-raising and referral pathway pilot in Bristol, North Somerset and South Gloucestershire, a general practice-based PrEP clinic in Lewisham, and a North East London pilot combining online assessment, postal kits, and delivery through GP and community settings. (2,19,20) This question is especially timely in the context of a rapidly evolving long-acting PrEP landscape, including the recent PURPOSE 1 and PURPOSE 2 trial results for twice-yearly lenacapavir and the ongoing PURPOSE 5 study in the UK and France. (12,13,21) In parallel, SHARE is leading the Beyond the Clinic pre-implementation study, which evaluates the prospective and hypothetical feasibility of delivering injectable PrEP in community settings in an equitable way. (22) The ongoing SHARE co-produced PrEP-Position pre-implementation study is examining PrEP knowledge, needs and preferences among underserved groups in the UK and has informed the community priorities and sampling approach for this programme. (23) The study found that 89% of participants showed the strongest interest in long-acting injectable modalities and that this preference was consistent across key populations. Furthermore, participants indicated that community-based provision would address exposure barriers that clinics NHS cannot. (24) The SHARE-led 'Beyond the Clinic' pre-implementation study elicited perspectives from healthcare providers across 89 sexual health services across the UK on potential to deliver injectable CAB delivery within sexual clinics and in community settings within the next 3-5 years. The study found that 86% (N=89) of respondents somewhat to strongly agreed that delivery of LA-PrEP within sexual health services was feasible within the next 3-5 years. HCPs identified funding and capacity, compatibility with existing service set-up, implementing clinical guidance and facilitating equitable uptake as key challenges to in-clinic implementation. (24) Respondents identified the most feasible potential delivery locations outside of sexual health clinics as: GP clinics, drug and alcohol services, prisons, voluntary sector, community pharmacies, homelessness services, women's health hubs. However, only 28% of respondents somewhat or strongly believed that community delivery was possible within 3-5 years. This exemplifies the need for this study.

Finally, SHARE also previously led the ILANA study, which showed that an intentionally equity-focused approach where recruitment targets were set across key populations successfully supported inclusive implementation of long-acting injectable HIV treatment in UK clinic and community settings. (25) PrEP-LANA extends that implementation and equity-focused approach to HIV prevention and will generate real-world UK evidence on how LA CAB PrEP delivery functions within and outside of NHS sexual health clinics among a diverse population of PrEP users.

Risks / benefits Risks The study is considered low risk. No clinical interventions are being performed. Clinical monitoring is per standard of care for PrEP users as all participants are already receiving CAB as PrEP as part of their NHS care so there is no additional clinical risk to participants. Any side effects of LA CAB will be managed according to locally agreed NHS protocols based on the product label.

Data collection risks

Minimal risks are involved in data collection for this study. Potential risks include:

• Quantitative data collection (PrEP users): There is a potential risk of data breach. This will be mitigated through strict adherence to the General Data Protection Regulation (GDPR) and institutional data security policies.
• Survey data collection (PrEP users): Pseudonymised data will be collected via an online survey. The survey will be as brief as possible and pretested to minimise time burden on participants. Participants who may experience difficulties completing an online survey will be offered appropriate support, including side-by-side support or guidance from a research team member.
• Qualitative data collection (HCP): Risks are minimal but may include time burden or professional discomfort when discussing service delivery challenges. Participation will be voluntary, and participants may decline to answer any questions or withdraw at any time without consequence and will be referred appropriately for support according to clear procedures detailed below if applicable.

Participant distress There is a potential risk of emotional distress, particularly when discussing experiences of stigma related to sexual history (including sex work) or gender identity, HIV risk, and intimate partner violence.

To mitigate this:

• Survey and interview materials have been co-designed with the PPIE Steering Group, including individuals with lived experience of PrEP Use, HIV-related and intersectional stigma, to ensure sensitivity and appropriateness.

• Should participants experience distress in relation to discussions around stigma related to HIV risk, sexually transmitted infections, gender identity or intimate partner violence they will be signposted to appropriate support organisations specialising in this area such as The Sophia Forum (support around HIV and sexual health stigma for cis and transgender women), The LoveTank CIC ( support around HIV and sexual health stigma for cis and transgender men), and Refuge (an intimate partner violence charity). The interviewer will also offer to contact the study site PI (with their permission), so that support can be offered locally by the clinical team at that study site.

• Researchers conducting qualitative data collection are experienced and trained in handling sensitive topics. They will:

  • Acknowledge participant discomfort
  • Offer breaks during data collection
  • Allow participants to specify that they prefer not to answer a specific question or discontinue specific topics
  • Support participants to withdraw entirely if desired Data Protection and Confidentiality

The Chief Investigator (CI) will act as the data custodian for all study data. The CI and wider study team will ensure that:

• Participant confidentiality is maintained at all stages
• All data are securely stored and handled in accordance with GDPR and institutional policies
• Identifiable information is minimised and protected Recruitment and Engagement Risks

There is a potential risk of limited participant engagement affecting recruitment targets. To mitigate this:

• Detailed feasibility assessments on ability to recruit key populations have been conducted at all participating sites and all principal investigators are committed to support the equity-focused approach detailed in the study.
• Recruitment will be closely monitored throughout the study.
• Efforts will be made to ensure inclusion of a diverse and representative sample, including racially minoritised communities, cis women, and migrant, transgender, and non-binary populations including a recruitment video which showcases the voices of under-represented groups.
• The study team will continue to work with the PPIE Steering Group to adapt recruitment strategies as needed

Benefits Participants in the clinical trials of CAB PrEP have found the injections to be more effective than oral PrEP. (26,27)

NHS Trusts are still adapting to the delivery of LA CAB, following previous provision of oral PrEP primarily by sexual health clinics. As a result of LA CAB being recently approved for PrEP by NICE, access may be limited initially, with clinic staff prioritising individuals based on need and personal circumstances. This study will generate learning from questionnaires and interviews about how best to deliver LA CAB within sexual health clinics and outside of sexual health clinics in non-specialist settings (e.g. general practitioner (GP) clinics, community pharmacies, drug and alcohol services, prisons, women's health hubs, homelessness services). These findings may improve service delivery for participants involved in the study and inform future implementation in other sexual health services, both nationally and internationally.

Study objectives Our overarching aim is to generate the evidence required to optimise the equitable delivery of LA CAB for PrEP among underserved populations within NHS sexual health services in the UK.

We will do this by:

1. Describing persistence on LA CAB
2. Describing implementation outcomes at individual and healthcare provider level.
3. Developing blueprints (standard operating procedures) for equitable delivery within and outside sexual health clinics that can be scaled and adapted in NHS clinics.

To ensure that people who are new to all PrEP modalities are included, at least 15% (n=30) of the total participants will be new users of PrEP.

A core principle of equity (understanding any difference in impact on underserved populations) will be applied throughout the study. To ensure representation of a diverse group of participants that reflects the demographic groups most affected by incident HIV and most underserved by PrEP in the UK, enrolment targets will be applied and meticulously managed by the central study team, as follows:

• A cap of 30% (n=60) will be applied to recruitment of White cisgender men who have sex with men who are not otherwise part of other under-represented groups (as defined below),
• At least 70%% (n=140) of participants will represent groups currently underserved by PrEP and fall into one (or more) of the following socio-demographic categories: women (defined cisgender or transgender) OR as transgender men OR non-binary individuals OR age<25 yrs, OR sex workers OR people who inject drugs OR racially minoritised heterosexual men.

Inclusion Criteria:

Participants of any gender, ethnicity or socio-economic group who meet all the following criteria are eligible for inclusion in this study:

• Adults who are aged > 18 years at time of consent (including people of child-bearing capacity and age, non-pregnant or pregnant adults)
• Attending a participating NHS sexual healthcare service
• Prescribed LA CAB for PrEP according to NICE and NHS eligibility criteria (including those newly prescribed and those already using LA CAB)
• Non-reactive / negative HIV Antigen/Antibody test and HIV RNA test at time of LA CAB for PrEP initiation (performed under routine care)
• Able and willing and able to give informed consent to all study procedures prior to inclusion

Exclusion Criteria:

PrEP user participants who meet any of the following criteria are ineligible for inclusion in this study:

• One or more reactive or positive HIV test results at enrolment visit, even if HIV infection is not confirmed.
• Currently enrolled in interventional trial of PrEP agents, HIV vaccine trial or experimental medication.
• Plan to relocate out of the area during the study period. Note: "Plan to relocate out of the area" is defined as a stated intention at enrolment to move residence outside the catchment area of a participating study site during the study period, such that ongoing clinical management would likely transfer to a non-participating team.