Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US)

Inclusion Criteria

• Be able to understand and comply with protocol requirements, instructions, and restrictions;
• Understand the long-term commitment to the study and be likely to complete the study as planned;
• Be considered appropriate candidates for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).

All Participants eligible for enrolment in the study must meet all of the following criteria:

• Aged 18 years or older at the time of signing the informed consent.
• HIV-1 infected and must be on an active highly active antiretroviral therapy (HAART) (2 or 3 drug) 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 treatment failure (HIV-1 RNA >=200 c/mL).

Acceptable stable ARV regimens prior to Screening include 2 NRTIs plus:

• INI (either the initial or second Combination antiretroviral therapy (cART) regimen)
• NNRTI (either the initial or second cART regimen)
• Boosted prediction interval (PI) (or atazanavir [ATV] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability)
• Any suppressed participants on a triple ART regimen for at least 6 months who had their regimen switched to a 2DR of dolutegravir (DTG)/RPV
• Documented evidence of at least two plasma HIV-1 RNA measurements =50 c/mL;
• During the previous 12 months, any confirmed HIV-1 RNA measurement >=200 c/mL Exclusionary medical conditions
• 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, except cutaneous Kaposi's sarcoma not requiring systemic therapy, and Cluster of Differentiation (CD4+) counts 3.25 is exclusionary
• Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula: (Age x AST) / (Platelets x ( sqr [ 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 ( 450 milli second (msec) or QTc (Bazett) >480 msec for subjects with bundle branch block). Exclusionary Laboratory Values or Clinical Assessments (a single rep