Correspondence to Dr Eugenia Negredo; [email protected]
STRENGTHS AND LIMITATIONS OF THIS STUDY
The HOLA study used verified implementation research methods in HIV healthcare that will generate the knowledge required for policymakers, healthcare mediators and the community to modify the current models of care in people living with HIV (PWH) towards a patient-centred approach.
The study includes the participation of community centres and Sexually Transmitted Infections (STI) clinics due to their proximity with PWH and their implication in pre-exposure prophylaxis implementation and rapid HIV diagnosis.
The study addresses not only urban tertiary centres but also rural centres.
It is important to note that the intervention is not exempt from certain risks, such as staff changes or logistic inconveniences, and planning for these in advance is at the expense of investigator criteria from each centre.
Per protocol, a medical visit at the hospital at months 6 and 12 had to be included for routine medical care, including those participants who have been randomised to receive treatment at the out-of-hospital centre.
Introduction
The Joint United Nations Programme on HIV/AIDS (UNAIDS) is a strategic programme aimed at guiding and coordinating governments and structures that are responsible for providing HIV services in order to save lives.1 Until 2020, the objectives were to ensure that 90% of people living with HIV (PWH) were diagnosed, 90% of them on antiretroviral treatment (ART) and 90% of them virally suppressed, and these have been updated to 95-95-95 for 2025. With this purpose, ‘Treat All’ policies in many regions worldwide have favoured access to ART, consequently reducing HIV-related morbidity and mortality, and increasing life expectancy in PWH. Thus, HIV treatment has shifted to a chronic care model of disease management.2 Currently, there are many potent, convenient and well-tolerated antiretroviral combinations available. However, ART should be prescribed as early as possible and, for the moment, in a life-lasting manner.
Nevertheless, stigma is still present, and recent goals by the UNAIDS include a novel target of quality-of-life improvement.1–3 In line with this, inclusion of patient-reported outcomes (PROs) is becoming a preference in the development of the latest clinical trials as these may shed light on which factors related to ART and patient care are of utmost importance in improving health-related quality of life, patient satisfaction and in reducing stigma. In particular, a recent study carried out in Germany found out that the frequency of dosing and the risk of long-term side effects have a major influence on the acceptance of novel therapy regimens and should be considered to increase patient adherence and satisfaction.4
Considering these reasons, there is a need for more convenient, less frequent treatment to help address the challenges associated with posology, psychosocial issues and adherence in PWH. Long-acting (LA) injectable regimens are emerging as a treatment option that may simplify therapy for PWH and anticipate a shift in the treatment paradigm for these people.5 There are data confirming the non-inferiority of the LA intramuscular (IM) cabotegravir (CAB) and rilpivirine (RPV) compared with continuing a standard-of-care regimen in antiretroviral-naive adults with HIV-1 suppressed after 20 weeks in oral ARV with DTG/ABC/3TC (FLAIR study)6 and for the maintenance of viral suppression (ATLAS, ATLAS-2M and LATTE-2 studies).7 8 Additionally, the use of CAB+RPV LA reduces the frequency of dosing from daily to every 2 months and may aid in addressing fear of disclosure, anxiety around medication adherence and daily reminders of the HIV status and the chronicity of disease.9
Nonetheless, in Spain, this LA regimen must be administered in the hospital by a trained health team every 2 months, supposing a change in the dynamics of HIV units, which were previously reserved for a medical visit every 6 months. For these reasons, this option could be less convenient than conventional daily oral therapy for some people since it implies visits to the hospital every 2 months for the administration of the injections. A shared approach for the treatment administration with primary care or community centres may be appropriate to improve the patient’s satisfaction while maintaining high-quality care for PWH. However, there is still insufficient evidence regarding the feasibility of decentralising treatment for PWH, particularly in the context of Spain.
Given these considerations, the proposed study seeks to address these issues by implementing the out-of-hospital CAB+RPV LA administration. Alternative settings to receive CAB+RPV LA will offer new options to PWH that may increase their quality of life and improve psychosocial challenges. Together with primary care centres, we are also interested in including community centres and sexually transmitted infection (STI) clinics due to their proximity with PWH and their implication in pre-exposure prophylaxis and rapid HIV diagnosis. Furthermore, centres belong to two different regions from Spain, including not only urban tertiary centres but also rural centres.
Research questions
To assess the implementability of this approach in Spain, first, we propose a comparison of the acceptability, appropriateness and feasibility of the administration of CAB+RPV LA between out-of-hospital settings and the local standard of care (hospital administration), as well as the patient’s satisfaction. The study is also focused on the identification of the PWH profile who are the best candidates to this strategy and whose satisfaction is higher. Finally, we will distinguish patients who are naïve to CAB+RPV LA from those who are not to evaluate potential intra-group differences.
The study is using Proctor’s research framework for measuring the success of specific implementation outcomes,10 according to which acceptability is defined as the perception among implementation stakeholders that a given treatment, service, practice or innovation (the administration of CAB+RPV LA in alternative injection sites) is satisfactory. Appropriateness is defined as the perceived compatibility of the innovation or evidence-based practice for a given practice setting, provider or consumer; and/or to address a particular issue. Finally, feasibility is defined as the extent to which the innovation can be successfully carried out within a given setting. Validity of these tools has been scientifically proven.11
Aims and objectives
The primary objective of this postapproval study is to assess and compare the acceptability by the patient of the implementation of CAB+RPV LA from the perspective of participants receiving outside-hospital injections versus the participants receiving hospital injections by month 12 in order to support future scale-up efforts. A co-primary objective of the study will be to assess and compare the safety and tolerability of CAB+RPV LA between the out-of-hospital administration and the in-hospital administration groups.
Secondary objectives are to assess and compare the acceptability, appropriateness and feasibility of the administration of CAB+RPV LA as perceived by patients and healthcare professionals (HCP)/non-clinical staff, as well as patient’s satisfaction and expectations throughout all timepoints of the study; retention, engagement and compliance; and to identify those patients in which the out-of-hospital administration is more suitable. Tertiary objectives are to assess and compare between groups the virological effectiveness; the change at month 12 versus baseline in patients’ acceptability, satisfaction and expectations among the subgroup of participants with previous experience with CAB+RPV LA; and to compare these with those patients who have never received CAB+RPV LA.
Methods and analysis
Study design
This is a 12-month, randomised, hybrid implementation-effectiveness, phase IV, double-arm, open-label, multicentric study including virologically suppressed PWH who start or are currently under treatment with CAB+RPV LA, to evaluate the out-of-hospital versus in-hospital administration of this combination in terms of acceptability, appropriateness, feasibility and satisfaction. Here, ‘hospital’ refers to HIV specialty outpatient clinics within tertiary care centres, while ‘out-of-hospital’ refers to other medical settings such as community-based care facilities, STI centres or primary care centres.
The study began in the preparation stage, where healthcare staff were engaged, informed and trained in CAB+RPV LA and the delivery strategies. All processes and protocols were ensured to be in place before the first patient was enrolled, and adequate material and human resources were provided. Community and primary care healthcare workers were trained to help deliver the injections to patients.
The study then transitioned into the initial implementation stage when the first patients were recruited and enrolled. Patients were randomised 1:1 into an in-hospital group or out-of-hospital group and stratified according to age (<50 years old or ≥50), gender (male or female), as well as according to whether participants are already receiving CAB+RPV LA. Rural and non-rural options were only considered in the out-of-hospital setting, and the choice was made by the participant. As of October 2023, the first participant was enrolled. PWH naïve to CAB+RPV LA during the oral treatment lead-in phase are attended at the reference hospital to rule out adverse events (AEs), and the first injection is administered in the hospital. They start receiving CAB+RPV LA injection doses at their in-hospital or out-of-hospital assigned centre from the next CAB+RPV LA administration (month 2). For patients previously receiving CAB+RPV LA, the first study injection is given in the randomised centre, at month 2.
No changes in treatment regimens are foreseen during the study period. In case of failure of one of the regimens, a new regimen will be decided using a resistance test as clinical routine. In case AEs to the medication occur, the investigator will decide if it is necessary to replace it.
Investigators may provide oral CAB and/or RPV as a short-term ‘bridging’ strategy for participants who have begun CAB+RPV LA in case a patient cannot attend an appointment. Should a participant need ‘oral bridging’, sites must contact the coordinating investigators for guidance on treatment strategies prior to a missed CAB+RPV LA dose, and the missed dose should be accurately noted in the registry. Bridge to oral therapy with CAB+RPV is permitted if a patient misses an injection. However, no more than two missing injections will be allowed as part of the study.
At the end of the study, the change of treatment will be done at the discretion of the physician.
Study setting
The study takes place at nine clinical units in two regions of Spain, Catalonia and Andalusia (3 tertiary hospitals (recruiting centres), one community centre, one STI clinic and four primary care centres) (table 1) and spans two implementation stages: preparation and initial implementation.
Table 1List of affiliated primary care or community centres and its hospitals of reference
| Reference hospital | Primary care centre/community centre |
| Hospital Universitari Germans Trias i Pujol (Catalonia) | BCN Checkpoint |
| CAP Dr. Robert | |
| Hospital Universitari General de la Vall d'Hebron (Catalonia) | Centre de Salut Internacional i Malalties |
| Transmissibles Drassanes—Vall d'Hebron | |
| Hospital Costa del Sol (Andalucia) | Centro de Salud San Pedro Alcántara |
| Centro de Salud San Luis de Sabinillas | |
| Centro de Salud Leganitos |
Outcome measures
The study includes both participant outcomes and staff outcomes, divided between primary, secondary and exploratory outcome measures:
Primary outcome measures:
To assess and compare between groups the number of participants that show a mean score ≥4 across the Acceptability of Intervention Measure (AIM) questionnaire at month 12.11–13
To assess and compare between groups the proportion of participants with a mean score ≥4 across the AIM questionnaires at month 12.
To assess and compare between groups the mean score across the AIM questionnaires at month 12.
To assess and compare between groups the incidence and severity of CAB+RPV LA-related AEs, all serious adverse events (SAEs), injection-site reactions or postinjection reactions through study completion, and the proportion of patients who presented grade 3 or 4 CAB+RPV LA-related AEs.
To assess and compare between groups the proportion of participants who discontinue CAB+RPV LA due to AEs/SAEs and due to CAB+RPV LA-related AEs.
Secondary outcomes measures:
To assess and compare between groups the proportion of participants with a mean score ≥4 across the AIM questionnaires at months 1 and 6.
To assess and compare between groups the proportion of participants with a mean score ≥4 across the Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM) questionnaires at months 1, 6 and 12.11–13
To assess and compare between groups the proportion of healthcare professionals and/or non-clinical staff that show a mean score ≥4 across the AIM, IAM and FIM questionnaires at months 1, 6 and 12.
To assess and compare between groups the proportion of patients who report high satisfaction at each study timepoints using the HIV Treatment Satisfaction Questionnaire ‘status’ (HIVTSQs12).14
To assess and compare between groups changes in satisfaction derived from HIVTSQs12, in the overall sample from baseline to months 1, 6 and 12.
To assess and compare between groups changes in satisfaction derived from the HIV Treatment Satisfaction Questionnaire ‘change’ (HIVTSQc12)14 in the overall sample from baseline to month 12.
To assess and compare between groups the expectations of the CAB+RPV LA regarding the following areas: adherence to treatment, follow-up of medical visits, illness perception, physical and emotional quality of life, family and social relationships and work; at baseline and months 6 and 12. Expectations will be assessed through 5-point Likert scales developed ad hoc for the study.
To assess and compare between groups the patient-reported outcome measures (PROMs) at each study timepoints using the Patient Reported Outcome Measures HIV Clinic Screening Tool (PROMS-CST- HIV) questionnaire,15 at baseline and months 1, 6 and 12. This questionnaire assesses PROs regarding anticipated stigma, emotional distress, sexuality, social support, material deprivation, sleep and fatigue, cognitive problems and physical symptoms.
To assess and compare between groups changes in PROMs throughout the timepoints in each group in the overall sample using the PROMS-CST- HIV questionnaire.
To assess and compare between groups changes in the health professionals’ expectations using a 5-point Likert Health Professional Expectations Questionnaire developed ad hoc for the study through study completion.
To assess and compare between groups the perception of injection (PIN), using the PIN questionnaire16 at months 1, 2, 4, 6, 8, 10 and 12.
To assess and compare between groups the proportion and number of patients who miss their appointment for the CAB+RPV LA administration (out of the window period±7 days) from baseline to months 6 and 12.
To assess and compare between groups the number and proportion of patients who early interrupt CAB+RPV LA at months 6 and 12.
To compare among groups the proportion of patients who adopt oral bridging therapy.
To identify those patients in which the out-of-hospital administration is more suitable by comparing the previous endpoints, stratifying according to age (<50 vs ≥50 years old), gender (male vs female), as well as according to if the participant is already receiving or not CAB+RPV LA.
Exploratory outcomes measures:
To assess and compare between groups the virological effectiveness of CAB+RPV LA at months 6 and 12:
Proportion of subjects who are virologically suppressed (plasma HIV-1 RNA ≤50 copies/mL).
Proportion of participants with confirmed virological failure/rebound (two consecutive HIV-1 RNA ≥200 copies/mL).
Proportion of participants with blips.
To assess the average change from baseline to month 12 in patients’ acceptability, satisfaction and expectations (AIM, HIVTSQs12, HIVTSQc12, expectations and PROMS-CST-HIV), as mentioned above, among the subgroup of participants with previous experience with CAB+RPV LA.
To compare patients’ acceptability, satisfaction and expectations at month 12 (AIM, HIVTSQs12, HIVTSQc12, expectations and PROMS-CST-HIV), as mentioned above, between patients under prior treatment with CAB+RPV LA and those patients who have never received CAB+RPV LA.
Patient and public involvement
Patients were not directly involved in the design of this study. However, the study addresses priorities relevant to patient care and outcomes, aligning with broader public health needs identified in previous research and clinical guidelines. In the dissemination phase, the results are planned to be shared with local community health organisations to inform future strategies and policies that directly impact patient care.
Sample size
A total of 110 virologically suppressed PWH will be included in this study and will receive CAB+RPV LA in the hospital and/or out-of-hospital alternative facilities. A period of enrolment of 8 months was considered.
Sample size justification
The sample size was calculated accepting an alpha error of 5%, for a statistical power of 80% in a bilateral contrast, and an expected acceptability of 45% in the hospital group and of 75% for the outpatient group, at the end of study. Fixing the type I error at 5%, 55 subjects per group will be necessary to reject the equal null hypothesis with a power of 80%. Assuming a maximum loss of 25%, the required sample size is 110 patients, 55 in each arm.
Participant identification
Potential participants who will be receiving or are receiving CAB+RPV LA within their routine clinical care are referred to the study team by their physicians within the HIV clinics of the three main hospitals. The local HIV teams then inform participants of the trial and provide patient information leaflets with contact details of the study team. Participants are scheduled for a screening visit, during which inclusion and exclusion criteria are revised and informed consent forms are signed as guided by the study nurses. Once the participants have signed the informed consent, they are randomised by a study nurse.
The randomisation list will be created using a uniform distribution and assigning a range of values to each group. The distribution between the branches A and B will be 1:1. The assignment will be made by the electronic Case Report Form (eCRF). It will be impossible for the investigators to know which group will be assigned to a patient before his/her inclusion in the study. Stratification will be made according to age (<50 years old or ≥50), gender (male or female) and according to whether the participant is already receiving or not CAB+RPV LA.
Inclusion and exclusion criteria
Adult PWH (age≥18 years) will be invited to participate if they have the capacity to consent with the following criteria:
Chronic HIV-1 infection.
Will receive CAB+RPV LA as part of their routine clinical care.
Recommended triple or dual therapy for at least 12 months, including CAB+RPV LA.
Virological suppression for at least 6 months (two consecutive determinations of undetectable viral load).
Postmenopausal or fertile females who agree to avoid pregnancy during the study. If sexually active female; using an effective method of contraception (hormonal contraception, intrauterine device or anatomical sterility in self or partner from 14 days prior to the first Investigational Medicinal Product (IMP) administration until at least 13 months after the last IMP administration); all female participants must be willing to undergo urine pregnancy tests at timepoints specified in the protocol.
Patients who have access to an out-of-hospital centre without inconvenience.
Patients who agree to participate in the study and sign the informed consent. An example of the informed consent form is provided in online supplemental materials.
Exclusion criteria:
Active hepatitis B infection.
History of virological failure or mutations to integrase strand transfer inhibitors or nucleoside reverse transcriptase inhibitors.
Previous ART interruption during the last 6 months or treatment interruptions for more than a month.
Contraindication for intramuscular injections.
Pregnant or breastfeeding women or desiring to become pregnant in the near future.
Current use of the following concomitant treatment: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampicin/rifampin, rifapentine and St. John’s wort.
Data collection
All participating sites will be assessed using a mixed-methods approach, including questionnaires, templated data collection instruments and primary data sources (clinic records). Blinding is not applicable since it is an open clinical trial.
Data management and monitorisation is under ScienHub. A data management system will be set up, and procedures will be implemented to warrant homogenisation, traceability and data quality. Data will be entered in a study-specific eCRF. Quality control procedures will be put in place for data checking. Rigorous consistency checks will be created in order to reduce errors during data entry. In the study, eCRF-codified data will be collected and stored, without including any personal data. The eCRF will be accessible to the sponsor, the data management team, the investigators and the study staff with data entry permissions. Investigators and institutions will allow monitoring and audits by the health authorities or the sponsor giving direct access to data and original source documents. Access to personal patient information will be restricted to the study physician/staff. To allow monitoring, audits and inspections, access to data to health authorities (Spanish Agency for Medicines and Health Products), the ethics committee and personnel authorised by the sponsor is guaranteed while maintaining the confidentiality thereof according to current legislation.
Treatment compliance and concomitant treatment
CAB+RPV LA compliance is guaranteed because study medication is to be administered by a designated study nurse at the clinical site. If the participant does not attend any visit, this information will be documented in the CRF.
All other treatments taken, apart from the study medication administered during the study period, will be considered concomitant treatments and should be documented in the CRF. Patients who participate in the study will be reminded that they should not start any new or continue any concomitant treatment without the knowledge and permission of the investigator. If discomfort following injection occurs, dosing with paracetamol 1 g every 8 hours for a total of 24 hours will be allowed, but never as a prophylaxis treatment. If discomfort persists, the patient must seek medical attention.
The following medications must not be administered concurrently: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampicin/rifampin, rifapentine, St. John’s wort and dexamethasone. In addition, the following treatments must be discontinued: proton pump inhibitors and systemic dexamethasone (more than a single dose). Use of anticoagulation agents greater than 14 days is prohibited, and systemic anticoagulation on the day of an IM injection should be avoided where possible.
Questionnaires
Participant questionnaires
Questionnaires will be provided to participants by nursing staff involved in the study during their scheduled clinic visit, at baseline, months 1, 6 and 12, except for the PIN questionnaire, which is to be filled in by the patient 2 days after injection, electronically.
Healthcare staff questionnaires
Staff will complete at baseline and at the end of the study (final test) a Health Professional Expectations Questionnaire. At months 1, 6 and 12, healthcare professionals and non-clinical staff will fill in the AIM/IAM/FIM health professional/non-clinical staff questionnaires.
Data analysis
Study data are collected through a study-specific/eCRF. All questionnaire data are collected directly on the eCRF by patients using an electronic device (tablets). All participants who passed screening and entered the study (ie, completed baseline eCRF) will be included in the analysis population. The staff who complete the study questionnaires will also be considered part of the study, and they will have an identification number and their role in the study (investigator, nurse, pharmacist, administrative staff).
The primary complete analyses will be conducted when the last study participant has completed their CAB+RPV LA study treatment up to month 12. All study staff participant (site-level) questionnaire, survey data and all study participant (subject-level) data will be included in the analysis. For the primary analysis on the primary endpoint at month 12, we will use the intention-to-treat (ITT-E) population. The ITT-E and per-protocol populations will be used for the secondary analyses and those on secondary aims. All the analyses on the primary and secondary objectives will be performed on the overall (total sample) population and by study arm. To evaluate the main objective, a comparison of the percentages of acceptability with a χ2 test will be made, and both the differences in percentages and the quotient of these percentages in the form of relative risk will be reported. Regarding some of the secondary and the exploratory objectives, a descriptive analysis will be performed.
Ethics and dissemination
The clinical trial will be conducted according to the principles of the Declaration of Helsinki, Fortaleza, Brazil, October 2013. This study will be conducted according to Spanish regulations regarding clinical trials (Royal Decree 1090/2015) and biomedical investigations (Organic Law 14/2007 of biomedical investigation and the Royal Decree 1716/2011), which develop the Clinical Trial Regulation (Regulation EU No 536/2014). Confidentiality requirements will follow the required Data Protection legislation. The current publication refers to V.3.0 of the protocol, with issue date 14 April 2024, as approved by the Comité de Ética de la Investigación con medicamentos del Hospital Universitari Germans Trias i Pujol (approval number AC-23-042-HGT-CEIM).
Final data exportation is scheduled for June 2025; until then, data are stored in a secured database where only selected investigators have access for purely assistance reasons. Following data exportation, statistical analyses will follow, with complete data sets expected for the first quarter of 2026. After finishing the study, the coordinating teams of the study will discuss the results and strategies for the future, as well as the data dissemination plan, in order to maximise the impact of this work on clinical care and policy. At least one manuscript is expected to be sent for publication covering the main results of the HOLA study. Subsequent subanalyses will be considered by the investigators if they deem appropriate. Once data are made available to the researchers participating in the study, data generated that support the final results article will be made available as soon as possible, wherever legally and ethically possible, on request. The publication of the trial results shall meet the requirements set out in Article 42 of Royal Decree 1090/2015. An individual personal statement according to the ICMJE guidelines is available in the clinical trial registry (NCT06185452). Results that emerge from this study will be reported in the HIV national and international meetings as well as published in international journals with high impact factor. If the outcome is deemed positive, we will also develop and propose policy guidelines for the integration of the administration of CAB+RPV LA in alternative outpatient facilities into the standard of care in the HIV care pathway. In addition to this study, a qualitative substudy, with a different study code (NCT: NCT06643897), has been conducted. The objective of the substudy is to assess the barriers and solutions for the implementation by interviewing the staff participating in the HOLA study. The substudy analyses are underway and will be published as well.
Discussion
In the current clinical programmes in Spain, the CAB+RPV LA formulation must be administered by a trained health team every 2 months in the hospital. Bringing treatment closer to patients may bring benefits to them in terms of satisfaction and reduction of stigma. However, evidence in the feasibility of the out-of-hospital delivery of CAB+RPV LA in Spain is non-existent. Implementation outcome measures are essential for monitoring and evaluating the feasibility of a change in procedures, such as the one described.11 Prior evidence in implementation science for this treatment comes mainly from the Cabotegravir and Rilpivirine Implementation Study in European Locations (CARISEL) study (a hybrid phase III implementation-effectiveness trial implementing CAB+RPV LA for PWH). This study was aimed at evaluating participants switching from daily oral therapy to CAB+RPV LA dosed every 2 months (Q2M). However, the Spanish sites participating in the trial were only hospitals, and no alternative outpatient centre was considered (CARISEL; NCT04399551).
In the CARISEL study, sites were randomised to standard implementation (Arm-S) or enhanced implementation (Arm-E), including additional implementation strategies. These enhancements were mainly focused on meetings that introduce CAB+RPV LA to clinic staff and discuss what might make implementation easier and/or what might make it difficult, prior to first injection at the site; and meetings started to discuss an implementation plan, how to work through challenges and introduce a continuous quality improvement plan, for 6 out of the 12 months of study. At month 12, regardless of the implementation arm, CAB+RPV LA was highly effective and well tolerated, consistent with clinical outcomes in the phase III clinical programme.17
Although HOLA has some similarity to CARISEL with respect to study outcomes, HOLA aims to examine the differences between clinic settings (urban and rural) as well as hospital and community-based settings for administering CAB+RPV LA through a set of three questionnaires that had been previously developed under the Proctor framework, as four-item measures of implementation outcomes that indicate implementation success10: the AIM, IAM and FIM questionnaires.11 Enrolment completion in the HOLA study took place by the end of May 2024, with an end of study expected in May 2025. It is important to note that the intervention is not exempt from certain risks, such as logistic inconveniences, so it is important to plan for these in advance.
The importance of implementation research in HIV healthcare relies on its potential to generate the knowledge required for policymakers, healthcare mediators and the community to modify the current models of care in PWH in order to improve their quality of life. The HOLA study may provide the required outcomes that will help bridge the gap towards a patient-centred approach in HIV care. The tools and methodology used for assessing implementation success have been validated and described previously as part of the Proctor framework,10 which gives value to decision-makers to consider the success of the intervention of study. In addition, a qualitative substudy, aiming to identify barriers and facilitators of the implementation of the administration of CAB+RPV LA in alternative facilities from the perspective of staff participating in the HOLA study, has been conducted. Data generated from both studies will contribute to the development of guidelines for implementation supporting governments and healthcare decision-makers in formulating successful implementation strategies.
This work has been carried out within the framework of the Doctoral Program in Medicine of the Autonomous University of Barcelona.
Ethics statements
Patient consent for publication
Not applicable.
Contributors EN (guarantor) and JO are the principal investigators of the study, initiated the conceptualization of the study, and coauthored the protocol with all the other authors. DHS is a clinical research fellow, and she converted the protocol into its publishable format. EN and DHS contributed equally to this paper. VF, PAL, CBC, LB, AR, JJ, MAC, ABF, and JMP are coinvestigators of the participating centers, and helped with implementation and patient recruitment. NL, DC, and VF are the hospital pharmaceutics and have contributed to implementation and protocol design. EN, DHS, LB, CM, JP, DR, and NL belong to the Coordinating Team at Hospital Germans Trias I Pujol and have helped in protocol design, trainings, and procedures of implementation, as well as in implementation support for other centers. JO, DA and FR belong to the Coordinating Team at Hospital Costa del Sol and have helped in trainings and procedures of implementation, as well as in implementation support for other centers.
Funding.The study has received funding from ViiV Healthcare (award number #219546).
Competing interests None of the authors have competing interests to declare in relation to this research. VFal, EN and JO have received fees for educational activities and/or consultancies and/or financial support for attending conferences from Gilead Science, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare outside of the submitted work. PA-L has received fees for educational activities from Janssen-Cilag and ViiV Healthcare outside of the submitted work. All other authors have no competing interest to declare.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
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Abstract
Introduction
The HOLA study is a 12-month randomised, hybrid implementation-effectiveness, phase IV, double-arm, open-label, multicentric study including virologically suppressed people living with HIV (PWH). HOLA, which started in September 2023, evaluates acceptability, appropriateness, feasibility and satisfaction of out-of-hospital administration of cabotegravir and rilpivirine long-acting (CAB+RPV LA).
Methods
A total of 110 PWH who are already under treatment with CAB+RPV LA or switch their antiretroviral therapy to CAB+RPV LA will be recruited from two main hospitals in Barcelona (Germans Trias I Pujol and Vall d’Hebrón) and Costa del Sol Hospital, in Marbella. The patients will be randomised 1:1 into a hospital group (administration of CAB+RPV LA in the hospital) and the outpatient group (out-of-hospital administration), including community or primary care centres. The main objectives of the study are to compare the acceptability at month 12 of the administration of CAB+RPV LA in and out-of-hospital centres from the perspective of patients, and assess and compare the safety and tolerability of CAB+RPV LA. The study takes place at nine clinical units in Catalonia and Andalusia (three tertiary hospitals (recruiting centres), one community centre, one sexually transmitted infection clinic and four primary care centres).
Ethics and dissemination
The current publication refers to V.3.0 of the protocol, with issue date 14 April 2024, as approved by the Comité de Ética de la Investigación con medicamentos del Hospital Universitari Germans Trias i Pujol (approval number AC-23-042-HGT-CEIM). The clinical trial will be conducted according to the principles of the Declaration of Helsinki, Fortaleza, Brazil, October 2013. This study will be conducted according to Spanish regulations regarding clinical trials (Royal Decree 1090/2015) and biomedical investigations (Organic Law 14/2007 of biomedical investigation and the Royal Decree 1716/2011), and the Clinical Trial Regulation (Regulation EU No 536/2014). Confidentiality requirements will follow the required Data Protection legislation. Enrolment completion in the study is expected by the end of May 2024, with an end of study expected in May 2025. Results emerging from this study will be reported in HIV national and international meetings as well as published in international journals with a high impact factor. If the outcome is deemed positive, we will also develop and propose policy guidelines for the integration of the administration of CAB+RPV LA in alternative outpatient facilities into the standard of care in the HIV care pathway.
Trial registration number
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Details
; Álvarez-López, Patricia 3 ; Falcó, Vicenç 4 ; Rivero, Àngel 5 ; Jusmet, Javier 6 ; Miguel Ángel Cuerda Palomo 7 ; Ana Belén Flores de la Cruz 8 ; Pavón, José Manuel 9 ; Llavero, Nadia 10 ; Campany, David 11 ; Faus, Vicente 12 ; Broto-Cortés, Claudia 3 ; Bailón, Lucía 13 ; Aguilar, Dámaris 14 ; Ruiz, Francis 14 ; Miranda, Cristina 13 ; Puig, Jordi 13 ; Rovira, David 13 ; Olalla, Julián 15 1 Fundacio Lluita contra les Infeccions, Badalona, Spain; UVic-UCC, Vic, Spain; Medicine, Autonomous University of Barcelona, Barcelona, Spain; CIBERINFEC, Madrid, Spain
2 Fundacio Lluita contra les Infeccions, Badalona, Spain; Medicine, Autonomous University of Barcelona, Barcelona, Spain
3 Centre de Salut Internacional i Malalties Transmissibles Drassanes - Vall d’Hebron, Barcelona, Spain
4 Medicine, Autonomous University of Barcelona, Barcelona, Spain; Vall d’Hebron University Hospital, Barcelona, Spain
5 Fundacio Lluita contra les Infeccions, Badalona, Spain; Projecte dels NOMS-Hispanosida, BCN CheckPoint, Barcelona, Spain
6 Centre de Atenció Primària Dr. Robert, Badalona, Spain
7 Centro de Salud de San Luis de Sabinillas, Málaga, Spain
8 Centro de Salud de San Pedro de Alcántara, Málaga, Spain
9 Centro de Salud Leganitos, Marbella, Spain
10 Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Spain
11 Pharmacy, Vall d'Hebron University Hospital, Barcelona, Spain
12 Pharmacy, Hospital Costa del Sol, Marbella, Spain
13 Fundacio Lluita contra les Infeccions, Badalona, Spain
14 Hospital Costa del Sol, Marbella, Spain
15 Infectious Diseases Unit, Hospital Costa del Sol, Marbella, Spain