A Study Evaluating Implementation Strategies for Cabotegravir (CAB)+ Rilpivirine (RPV) Long-acting (LA) Injectables for Human Immunodeficiency Virus (HIV)-1 Treatment in European Countries
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: CAB OLI; CAB LA; RPV OLI; RPV LA; Continuous Quality Improvement (CQI) calls
Intervention description: CAB will be available as 30 milligrams (mg) tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.; CAB LA 600 mg will be administered as intramuscular (IM) injection.; RPV will be available as 25 mg tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.; RPV LA 900 mg will be administered as IM injection.; CQI will be attended by the enhanced arm (Arm-E). The CQI calls will be conducted to identify problems/challenges, generate plans to address the challenges, and identify how to measure the change that results from the plan.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: This is an open-label study hence no blinding is required
Enrollment: 437.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cabotegravir; Rilpivirine; Long-acting injectables; Patient study participants; Staff study participants

Summary:

      The overall objective of the CAB LA + RPV LA clinical development program is to develop a
      highly effective, well-tolerated, two-drug, LA injectable regimen which has the potential to
      offer improved treatment convenience, compliance and improved quality of life for people
      living with HIV compared to current standard of care. This interventional study will examine
      different implementation strategies in different clinic settings across European countries to
      identify strategies which best meet the needs in each local context and involve both
      participants receiving study treatment CAB LA + RPV LA (patient study participants [PSP]) as
      well as the healthcare providers at the investigator site level (staff study participants
      [SSP]). SSPs consists of 2 groups: standard and enhanced arm.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants aged 18 years or older at the time of signing the informed consent.

          -  HIV-1 infected and must be suppressed on a guideline recommended active Highly active
             antiretroviral therapy (HAART) regimen for at least 6 months prior to screening. Any
             prior switch, defined as a change of a single drug or multiple drugs simultaneously,
             must have occurred due to tolerability/safety, access to medications, or
             convenience/simplification, and must not have been done for virologic failure (on
             treatment HIV-1 RNA more than or equal to [>=]200 c/mL).

          -  Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12
             months prior to Screening: at least one <6 months prior to screening and one 6-12
             months prior to screening.

          -  Plasma HIV-1 RNA <50 c/mL at screening.

          -  A female participant is eligible to participate if she is not pregnant (as confirmed
             by a negative urine human chorionic gonadotrophin [hCG] test at screen and at Day 1),
             not lactating, and at least one of the following conditions applies:

               1. Non-reproductive potential is defined as:

                  Pre-menopausal females with one of the following:

                    -  Documented tubal ligation.

                    -  Documented hysteroscopic tubal occlusion procedure with follow-up
                       confirmation of bilateral tubal occlusion.

                    -  Hysterectomy.

                    -  Documented Bilateral Oophorectomy.

                    -  Postmenopausal defined as 12 months of spontaneous amenorrhea [in
                       questionable cases a blood sample with simultaneous follicle stimulating
                       hormone (FSH) and estradiol levels consistent with menopause. Females on
                       hormone replacement therapy (HRT) and whose menopausal status is in doubt
                       will be required to use one of the highly effective contraception methods if
                       they wish to continue their HRT during the study. Otherwise, they must
                       discontinue HRT to allow confirmation of post-menopausal status prior to
                       study enrolment.

               2. Reproductive potential and agrees to follow one of the options listed in the
                  Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
                  Reproductive Potential (FRP) from 30 days prior to the first dose of study
                  medication, throughout the study, and for at least 30 days after discontinuation
                  of all oral study medications and for at least 52 weeks after discontinuation of
                  CAB LA and RPV LA.

          -  Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form and in this protocol.
             Eligible participants or their legal guardians (and next of kin when locally
             required), must sign a written informed consent form before any protocol-specified
             assessments are conducted. Enrolment of participants who are unable to provide direct
             informed consent is optional and will be based on local legal/regulatory requirements
             and site feasibility to conduct protocol procedures.

          -  French participants: In France, a participant will be eligible for inclusion in this
             study only if either affiliated to or a beneficiary of a social security category.

        Exclusion criteria:

          -  Within 6 months prior to screening, plasma HIV-1 RNA measurement >=50 c/mL.

          -  During the previous 12 months, any confirmed HIV-1 RNA measurement >=200 c/mL.

          -  Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during
             the study.

          -  Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3
             disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy,
             and historical or current Cluster of Differentiation 4 (CD4)+ counts <200 cells per
             millimeter cube (cells/mm^3) are not exclusionary.

          -  Any pre-existing physical or mental condition (including substance use disorder)
             which, in the opinion of the investigator, may interfere with the participant's
             ability to comply with the dosing schedule and/or protocol evaluations or which may
             compromise the safety of the participant.

          -  Participants determined by the investigator to have a high risk of seizures, including
             participants with an unstable or poorly controlled seizure disorder. A participant
             with a prior history of seizure may be considered for enrolment if the investigator
             believes the risk of seizure recurrence is low.

          -  Participants who, in the investigator's judgment, pose a significant suicide risk.
             Participant's recent history of suicidal behavior and/or suicidal ideation should be
             considered when evaluating for suicide risk.

          -  The participant has a tattoo, gluteal implant/ enhancements or other dermatological
             condition overlying the gluteus region which may interfere with interpretation of
             injection site reactions.

          -  Evidence of Hepatitis B virus (HBV) infection based on the results of testing for
             Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B
             surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows:

               -  Participants positive for HBsAg are excluded.

               -  Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg
                  status) and positive for HBV DNA are excluded.

          -  Participants who are anticipated to require Hepatitis C virus (HCV) treatment within
             12 months must be excluded. Asymptomatic individuals with chronic HCV infection will
             not be excluded; investigators must carefully assess if therapy specific for HCV
             infection is required. (HCV treatment on study may be permitted, following
             consultation and approval of the DAA based therapy being considered with the medical
             monitor).

          -  Participants with HCV co-infection will be allowed entry into this study if:

               1. Liver enzymes meet entry criteria.

               2. HCV disease has undergone appropriate work-up, and is not advanced. Additional
                  information (where available) on participants with HCV coinfection at screening
                  should include results from any liver biopsy, Fibroscan, ultrasound, or other
                  fibrosis evaluation, history of cirrhosis or other decompensated liver disease,
                  prior treatment, and timing/plan for HCV treatment.

               3. In the event that recent biopsy or imaging data is not available or inconclusive,
                  the Fib-4 score will be used to verify eligibility:

                    -  Fib-4 score more than (>)3.25 is exclusionary.

                    -  Fib-4 score 1.45-3.25 requires Medical Monitor consultation Fibrosis 4 score
                       formula:

        (Age times Aspartate aminotransferase [AST]) / (Platelets times (square [Alanine
        aminotransferase]{ALT}).

          -  Unstable liver disease (as defined by any of the following: presence of ascites,
             encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or
             persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of
             Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver
             disease per investigator assessment).

          -  History of liver cirrhosis with or without hepatitis viral co-infection.

          -  Ongoing or clinically relevant pancreatitis.

          -  Clinically significant cardiovascular disease, as defined by history/evidence of
             congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery
             bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty
             (PTCA) or any clinically significant cardiac disease.

          -  Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or
             resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial
             neoplasia; other localized malignancies require agreement between the investigator and
             the Study medical monitor for inclusion of the participant prior to inclusion.

          -  Any condition which, in the opinion of the Investigator, may interfere with the
             absorption, distribution, metabolism or excretion of the study drugs or render the
             participant unable to receive study medication.

          -  History or presence of allergy or intolerance to the study drugs or their components
             or drugs of their class. Current or anticipated need for chronic anti-coagulation with
             the exception of the use of low dose acetylsalicylic acid (less than or equal to
             [<=]325 mg per day) or hereditary coagulation and platelet disorders such as
             hemophilia or Von Willebrand Disease

          -  Any evidence of primary resistance based on the presence of any major known Integrase
             inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI)
             resistance-associated mutation, except for K103N, by any historical resistance test
             result.

          -  ALT >=5 times the upper limit of normal (ULN) or ALT >=3 times ULN and bilirubin >=1.5
             times ULN (with >35 percent [%] direct bilirubin).

          -  Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during
             the Screening phase to verify a result.

          -  Participant has estimated creatinine clearance <50 milliliters per minute
             (mL/min)/1.73 m^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
             equation.

          -  Exposure to an experimental drug or experimental vaccine within either 28 days, 5
             half-lives of the test agent, or twice the duration of the biological effect of the
             test agent, whichever is longer, prior to Day 1 of this study.

          -  Treatment with any of the following agents within 28 days of Day 1:

               -  Radiation therapy.

               -  Cytotoxic chemotherapeutic agents.

               -  Tuberculosis therapy except for isoniazid (isonicotinylhydrazid [INH]).

               -  Anti-coagulation agents.

               -  Immunomodulators that alter immune responses such as chronic systemic
                  corticosteroids, interleukins, or interferons.

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.

          -  Use of medications which are associated with Torsade de Pointes must be discussed with
             the Medical Monitor to determine eligibility.

          -  Participants receiving any prohibited medication and who are unwilling or unable to
             switch to an alternate medication.

          -  A participant with known or suspected active Coronavirus Disease 2019 (COVID-19)
             infection OR contact with an individual with known COVID-19, within 14 days of study
             enrollment (World Health Organization [WHO] definitions).