Clinical trial NCT05294159: Implementing Long-Acting Novel Antiretrovirals
Official title: Implementing Long-Acting Novel Antiretrovirals - the ILANA Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Viruses
Keywords: HIV-1
Long-acting antivirals
Implementation science
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: Chelsea and Westminster NHS Foundation Trust
name: Barts & The London NHS Trust
name: Guy's and St Thomas' NHS Foundation Trust
name: Royal Free Hospital NHS Foundation Trust
name: Liverpool University Hospitals NHS Foundation Trust
name: Brighton and Sussex University Hospitals NHS Trust
First posted: 2022-03-24
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 108 stable, virally suppressed PWH.

To achieve representation of underrepresented groups in HIV studies, a cap will be set on recruitment of men at 50%, white participants at 50% and age under 50y at 70%.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants that agree or completely agree (average score of 4 or higher) on the Feasibility of Intervention Measure (FIM) (a validated method)
timeFrame: 12 months
Secondary outcomes:
measure: 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
timeFrame: At Day 0, 4 Months and 12 Months
measure: 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)
timeFrame: At Day 0, 4 Months and 12 Months
measure: 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
timeFrame: At 8 months and 12 months
measure: Proportion of injections occurring within target window from target date (± 7 days of target date)
timeFrame: 12 months
measure: Proportion of injections occurring after target window with/without use of oral ART
timeFrame: 12 months
measure: Incidence and extent of oral bridging use
timeFrame: 12 months
measure: Qualitative interviews with nurses to ascertain the utility of the Blueprints by Community Nurse or Clinic Nurse
timeFrame: 12 months
measure: Questionnaire checklist of Blueprint activities documentation to ascertain adaptations to Blueprints
timeFrame: 12 months
measure: Qualitative interviews to ascertain the utility of Facilitation Calls to improve implementation from the HIV clinic staff, Community Nurses, Clinic Nurses
timeFrame: 12 months
measure: HIV Treatment Satisfaction Questionnaire (HIVTSQs-12) (a validated questionnaire) to assess and ascertain the change in treatment satisfaction score over time and by setting
timeFrame: 12 months
measure: Validated questionnaires to describe tolerability and acceptance of injections
timeFrame: 12 Months
measure: Validated questionnaires and qualitative interviews to ascertain participants' overall treatment experience preference and medical need for long-acting therapy
timeFrame: 12 Months
measure: Qualitative interviews to ascertain patient preference for setting they receive injections and the reasons for their choice
timeFrame: 12 Months
Other outcomes:
measure: Incidence of CAB and RPV LA related ADRs (adverse drug reactions) and all SAEs
timeFrame: 12 months
measure: Proportion of participants who do not progress to injections/discontinuation during oral lead in
timeFrame: 12 months
measure: Proportion of participants who discontinue CAB and RPV LA, for all cause, virological reasons or tolerability
timeFrame: 12 months
measure: Proportion of participants who are virologically suppressed (plasma HIV-1 RNA VL<50 c/mL) at month 4 and 12 (with +/- 6-week window)
timeFrame: 12 months
measure: Proportion participants with VL ≥ 50 c/mL at M4 and M12 (with a +/- 6-week window
timeFrame: 12 months
Locations:
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Blizard Institute
city: London
country: United Kingdom
facility: Royal Free Hospital NHS
city: London
country: United Kingdom
facility: Guys' and St Thomas' NHS Trust
city: London
country: United Kingdom
facility: Chelsea & Westminster NHS Foundation Trust
Study officials:
affiliation: QMUL
name: Chloe Orkin
role: STUDY_CHAIR
References:
citation: Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009 Aug 7;4:50. doi: 10.1186/1748-5908-4-50.
citation: Proctor E, Silmere H, Raghavan R, Hovmand P, Aarons G, Bunger A, Griffey R, Hensley M. Outcomes for implementation research: conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment Health. 2011 Mar;38(2):65-76. doi: 10.1007/s10488-010-0319-7.
citation: Weiner BJ, Lewis CC, Stanick C, Powell BJ, Dorsey CN, Clary AS, Boynton MH, Halko H. Psychometric assessment of three newly developed implementation outcome measures. Implement Sci. 2017 Aug 29;12(1):108. doi: 10.1186/s13012-017-0635-3.