Evaluation of Long-Acting Cabotegravir and Rilpivirine Administration in HIV-Infected Patients in Spain: Acceptability, Safety, and Feasibility Analysis

The primary objective of this study is to evaluate the **acceptability** of the administration of long-acting cabotegravir (CAB) and rilpivirine (RPV) at month 12 from the perspective of participants receiving outside-hospital injections compared to those receiving hospital injections. Additionally, the study aims to assess and compare the **safety** and **tolerability** of the long-acting CAB+RPV regimen. This is clinically relevant as it addresses the potential for improved patient adherence and satisfaction with HIV treatment regimens, which can lead to better health outcomes.

Secondary objectives include:

• Assessing and comparing the acceptability, appropriateness, and feasibility of the administration of LA CAB+RPV as perceived by patients and healthcare professionals/non-clinical staff at various intervals (month 1, month 6, and month 12).
• Evaluating patient satisfaction and expectations regarding treatment adherence, follow-up of medical visits, illness perception, quality of life, and social relationships.
• Assessing changes in Patient Reported Outcome Measures (PROMs) and health professionals' expectations.
• Comparing the perception of injection (PIN) and identifying patients for whom out-of-hospital administration is more suitable.
• Evaluating retention, engagement, and compliance, including the assessment of patients missing appointments, early interruption of treatment, and adoption of oral bridging therapy.

The clinical trial involves **HIV-infected patients** who are equal to or older than 18 years of age. Both male and female participants are included, with specific considerations for post-menopausal or fertile females who must agree to avoid pregnancy during the study. Participants must have a history of chronic HIV infection and have been prescribed LA CAB+RPV, with a recommended triple or dual therapy for at least 12 months, including CAB+RPV LA. They must also demonstrate virological suppression for at least 6 months, evidenced by two consecutive determinations of undetectable viral load. The study does not involve a vulnerable population. Participants are required to have access to an out-of-hospital center for treatment. The sponsor has not provided the total number of participants for this trial.

The clinical trial is designed to evaluate the **acceptability**, safety, and tolerability of a long-acting combination therapy of cabotegravir and rilpivirine in patients with **HIV**. This study is a randomized, double-blind, controlled trial with an estimated duration from September 2023 to March 2025. Participants will be randomly assigned to receive either out-of-hospital or hospital-administered injections of the long-acting therapy. The trial will include several key phases, beginning with a screening visit to confirm eligibility based on criteria such as age, chronic HIV infection, and virological suppression. Participants must have been on recommended therapy for at least 12 months and agree to avoid pregnancy during the study.

The trial will involve multiple study visits, including follow-up visits at months 1, 6, and 12, and an end-of-study visit. The primary endpoints will assess the acceptability of the therapy using the Acceptability Intervention Measure (AIM) questionnaire, with a focus on the proportion of participants achieving a composite score of 4 or higher. Secondary endpoints will evaluate patient satisfaction, healthcare provider perceptions, and the incidence of adverse events. The expected length of participant involvement is up to 12 months, with conditions for early termination including adverse events or withdrawal of consent.

Participants will receive either oral or intramuscular administration of the study drugs, with the maximum treatment period for oral administration being 1 month and for intramuscular administration being 12 months. The study aims to identify patient subgroups for whom out-of-hospital administration is most suitable, stratifying by age, gender, and prior experience with the therapy. The trial will also compare the number and proportion of patients who miss appointments or discontinue the therapy early. The study's findings will contribute to understanding the feasibility and satisfaction associated with long-acting antiretroviral therapy in a real-world setting.

The clinical trial involves the administration of several experimental medications, each with specific characteristics and administration protocols. **EDURANT** 25 mg film-coated tablets contain the active substance **rilpivirine**. These tablets are administered orally with a maximum daily dose of 25 mg and a total dose limit of 750 mg over a treatment period of one month. The pharmaceutical form is a film-coated tablet, and the medication is produced by Janssen-Cilag International NV. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

**REKAMBYS** 900 mg prolonged-release suspension for injection also contains **rilpivirine** as the active substance. This formulation is administered via intramuscular injection, with a maximum daily dose of 900 mg and a total dose limit of 5400 mg over a 12-month treatment period. The prolonged-release suspension is designed to maintain therapeutic levels of the drug over an extended period, reducing the frequency of administration. This product is also manufactured by Janssen-Cilag International NV.

**Vocabria** 600 mg prolonged-release suspension for injection contains the active substance **cabotegravir**. It is administered intramuscularly, with a maximum daily dose of 600 mg and a total dose limit of 3600 mg over a 12-month period. The prolonged-release formulation allows for sustained drug release, minimizing the need for frequent dosing. This medication is produced by ViiV Healthcare B.V., and participant compliance is monitored to ensure proper administration and adherence to the treatment regimen.

**Vocabria** 30 mg film-coated tablets contain **cabotegravir sodium** as the active substance. These tablets are administered orally, with a maximum daily dose of 30 mg and a total dose limit of 900 mg over a one-month treatment period. The film-coated tablet formulation is designed for ease of administration and patient compliance. ViiV Healthcare B.V. is the manufacturer of this product, and adherence to the dosing schedule is monitored throughout the trial.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the acceptability, safety, and tolerability of the long-acting combination of cabotegravir and rilpivirine in HIV-infected patients. Compliance monitoring is an integral part of the study to ensure accurate assessment of the treatment's efficacy and safety.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include evaluating the acceptability of the long-acting combination of cabotegravir and rilpivirine (LA CAB+RPV) using the Acceptability Intervention Measure (AIM) questionnaire. This will involve measuring the number and proportion of participants receiving injections who achieve an average composite score of ≥4 across the AIM questionnaires at month 12. Additionally, the safety and tolerability of LA CAB+RPV will be assessed by monitoring the incidence and severity of related adverse events (AEs), serious adverse events (SAEs), injection site reactions (ISRs), and post-injection reactions. The percentage of participants who discontinue LA CAB+RPV due to AEs or SAEs at any time, and specifically at months 6 and 12, will also be compared between groups.

Secondary endpoints will further explore the acceptability and satisfaction of the treatment. This includes the number and proportion of participants with an average composite score of ≥4 across the AIM, IAM, and FIM questionnaires at months 1, 6, and 12. The study will also assess patient satisfaction using the HIV Treatment Satisfaction Questionnaire (HIVTSQs12) and compare changes from baseline to months 1, 6, and 12. Patient-reported outcomes will be evaluated using the PROMs-CST-HIV questionnaire, and changes will be assessed from baseline to months 1, 6, and 12. The study will also compare the number and proportion of patients who miss appointments, early interrupt treatment, or withdraw from the study at months 6 and 12. Time to discontinuation of LA CAB+RPV and the adoption of oral bridging therapy during the 12-month period will be analyzed. The study aims to identify patients for whom out-of-hospital administration is more suitable by stratifying results according to age, gender, and prior experience with LA CAB+RPV.