Implementing Long-Acting Novel Antiretrovirals

Study Overview
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Brief Summary
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This is a 12-month, dual arm, phase 4, open-label, multi-centre study examining the implementation of LA intra-muscular (IM) drugs in clinics and decentralised community-based settings in the UK.

Detailed Description
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Cabotegravir and Rilpivirine (CAB+RPV) LA, is recommended in European US and British guidelines as a treatment for HIV-1 that allows PWH to receive a two-monthly injectable treatment, rather than daily pills. Providing injectable therapy in a system designed to provide and manage patients on oral treatments poses logistical challenges namely how resources are used to accommodate patient preference within a constrained health economy with capacity limitations. Exploring the use of alternative settings for injection, including community-based settings to deliver CAB+RPV LA, has the potential to expand options and potentially improve clinic capacity. Many PWH report high levels of stigma when attending the HIV clinic which can affect engagement with care, so receiving care in a community setting may provide additional choices and the possibility of receiving treatment in a less medicalized setting. Implementation studies in Europe are also assessing this in their countries. The National Health Service (NHS) in the UK is a very specific health environment where people are entitled to treatment and care which is free at the point of delivery. Unlike other medical specialties where primary care physicians are responsible for prescribing treatment for chronic conditions, PWH are managed and receive their HIV treatment in HIV and sexual health clinics. For the circa 105K people with HIV in the UK, outcomes are excellent. More than 95% of those on treatment have undetectable viral loads. However, around 8100 people in the UK are not able to take oral ART successfully. US guidelines have specified that LA CAB+ RPV is particularly important for those who experience pill fatigue, stigma and have fears of inadvertent disclosure. This is highly relevant to the ethnically diverse population of people in the UK living with HIV, many of whom come from marginalized and minoritized communities in which stigma is rife and in whom the treatment outcomes are the poorest. Women, racially minoritized people and older people are chronically under-represented in HIV clinical trials which is why we have set recruitment caps to ensure we recruit 50% women, 50% ethnically diverse people and 30% over 50 years of age. This is to ensure that we go beyond lip-service and hold ourselves to account in designing our trials with peer researcher involvement from the outset and committing to include a more representative study population. We will achieve this by engaging actively with community organisations to ensure awareness of this implementation trials. The study will be conducted at six large clinic sites both in London and outside of London. In this pragmatic real-world trial, each site will identify the most workable option to deliver of CAB+RPV LA according to SmPC license in the community setting within their region or borough.

Official Title
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Implementing Long-Acting Novel Antiretrovirals - the ILANA Study

Conditions
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Human Immunodeficiency Viruses

Intervention / Treatment
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* Other: The Feasibility of Intervention Measure (FIM) and Acceptability of Intervention Measure (AIM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Documented HIV-1 infection Virologically suppressed (HIV-1 RNA <50 copies/ml) on a stable antiretroviral regimen Able and willing to complete informed consent prior to inclusion No hepatitis B In accordance with EU license and NICE guidance Exclusion Criteria: Based on contraindication for CAB LA, RPV LA, in accordance with EU license and NICE guidance Prior virologic failure on substances of NNRTI or INI class Resistance mutations to any substance of the NNRTI or INI class Prior exposure to CAB + RPV LA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Clinic-based PLH on CAB+RPV LA<br>All PWH participants will begin injections in the clinic setting in Phase 1. During Phase 1, PWH participants are screened and consented to participate in the study. During the screening phase, potential participants will be asked to identify their preferred location for phase 2 (decentralised site) and the reason for their preference. At the time of consent, patients will select their injection setting for Phase 2. Patients can select their preferred choice of setting until the 50 in-clinic numbers and 100 decentralised site places have been reached. After this, PWH participants will be allocated to the setting yet to reach its cap. In Phase 2, PWH participants will either continue to receive injection in clinic or receive injections from community nurses or clinic nurses at decentralised sites. | Other: The Feasibility of Intervention Measure (FIM) and Acceptability of Intervention Measure (AIM)<br>* The Feasibility and Acceptability of Intervention Measure (FIM and AIM) are used to evaluate the feasibilit and acceptability of our implementation strategies. The FIM and AIM is a validated implementation outcome measure where higher scores indicate greater feasibility and acceptability<br>|
| Community-based PLH on CAB+RPV LA<br>All PWH participants will begin injections in the clinic setting in Phase 1. During Phase 1, PWH participants are screened and consented to participate in the study. During the screening phase, potential participants will be asked to identify their preferred location for phase 2 (decentralised site) and the reason for their preference. At the time of consent, patients will select their injection setting for Phase 2. Patients can select their preferred choice of setting until the 50 in-clinic numbers and 100 decentralised site places have been reached. After this, PWH participants will be allocated to the setting yet to reach its cap. In Phase 2, PWH participants will either continue to receive injection in clinic or receive injections from community nurses or clinic nurses at decentralised sites. | Other: The Feasibility of Intervention Measure (FIM) and Acceptability of Intervention Measure (AIM)<br>* The Feasibility and Acceptability of Intervention Measure (FIM and AIM) are used to evaluate the feasibilit and acceptability of our implementation strategies. The FIM and AIM is a validated implementation outcome measure where higher scores indicate greater feasibility and acceptability<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants that agree or completely agree (average score of 4 or higher) on the Feasibility of Intervention Measure (FIM) (a validated method) | To evaluate feasibility of CAB and RPV LA administration at clinics in England and community based settings by patients | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of care provider and nurse participants that agree or completely agree (average score of 4 or higher) on the FIM and via qualitative interviews | To evaluate feasibility of CAB and RPV LA administration at 6 English clinics and decentralised community settings by healthcare professionals (HCPs) | At Day 0, 4 Months and 12 Months | 
| Proportion of care provider and nurse participants that agree or completely agree (average score of 4 or higher) Acceptability of Intervention Measure (AIM) (a validated method) | To evaluate acceptability of CAB and RPV LA by participants and clinic staff | At Day 0, 4 Months and 12 Months | 
| Proportion of community site representatives that agree or completely agree (average score of 4 or higher) score of on the FIM and AIM with in-depth qualitative interviews with community site representative | To evaluate feasibility and acceptability of CAB and RPV LA by community site representatives | At 8 months and 12 months | 
| Proportion of injections occurring within target window from target date (± 7 days of target date) | To describe adherence to dosing window by clinicians | 12 months | 
| Proportion of injections occurring after target window with/without use of oral ART | To describe adherence to dosing window by clinicians | 12 months | 
| Incidence and extent of oral bridging use | To describe adherence to dosing window by clinicians | 12 months | 
| Qualitative interviews with nurses to ascertain the utility of the Blueprints by Community Nurse or Clinic Nurse | To evaluate the utility of the Blueprints by Community Nurse or Clinic Nurse | 12 months | 
| Questionnaire checklist of Blueprint activities documentation to ascertain adaptations to Blueprints | To evaluate the fidelity to Blueprint by Community Nurse or Clinic Nurse | 12 months | 
| Qualitative interviews to ascertain the utility of Facilitation Calls to improve implementation from the HIV clinic staff, Community Nurses, Clinic Nurses | To evaluate the utility of Facilitation Calls to improve implementation from the HIV clinic staff, Community Nurses, Clinic Nurses | 12 months | 
| HIV Treatment Satisfaction Questionnaire (HIVTSQs-12) (a validated questionnaire) to assess and ascertain the change in treatment satisfaction score over time and by setting | To describe the change in treatment satisfaction score over time and by setting | 12 months | 
| Validated questionnaires to describe tolerability and acceptance of injections | To describe tolerability and acceptance of injections | 12 Months | 
| Validated questionnaires and qualitative interviews to ascertain participants' overall treatment experience preference and medical need for long-acting therapy | To describe participants' overall treatment experience preference and medical need for long-acting therapy | 12 Months | 
| Qualitative interviews to ascertain patient preference for setting they receive injections and the reasons for their choice | To describe patient preference for setting they receive injections and the reasons for their choice | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, Long-acting antivirals, Implementation science