A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed

Exclusion Criteria

• •Within 6 months prior to Screening, any plasma HIV-1 RNA measurement \>=50 c/mL.
• •Within the 6 to 12-month window prior to Screening, documented evidence of any plasma HIV-1 RNA measurement greater than (\>)200 c/mL, or 2 or more plasma HIV-1 RNA measurements \>=50 c/mL.
• •History of prior treatment failure to any Department of Health and Human Services (DHHS) recommended ART regimen.
• •History of drug holiday \>1 month for any reason prior to Screening visit, except where all ART was stopped due to tolerability and/or safety concerns.
• •Any change to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement \>=200 c/mL after initial suppression to \<50 c/mL while on first line HIV therapy regimen).
• •Participants who are currently participating in or anticipate being selected for any other interventional study.
• •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 CD4+ counts \<200 cells/microliter are not exclusionary.
• •Participants with moderate to severe hepatic impairment.
• •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 enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrollment.
• •All participants will be screened for syphilis.
• •* Participants with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive rapid plasma reagin (RPR) and a positive treponemal test without clear documentation of treatment, are excluded.
• •* Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor.
• •* Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, participants may be rescreened once following completion of antibiotic therapy for primary or early latent secondary syphilis.
• •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 at Screening 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:
• •1. Participants positive for HBsAg are excluded.
• •2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded.
• •Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who require or qualify for immediate HCV treatment are excluded for those co-infected participants who post entry into Switch Onto Long Acting Regimen (SOLAR) decide treatment for HCV infection is warranted or desired either by the participant or by the treating physician.
• •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, and will not require treatment prior to the Month 14 visit. Additional information (where available) on participants with HCV co-infection 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 fibrosis (Fib)-4 score will be used to verify eligibility
• •i. Fib-4 score \>3.25 is exclusionary ii. Fib-4 scores 1.45-3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula: d. Age x aspartate aminotransferase (AST)/ Platelets x (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, or decompensated cirrhosis \[for example {e.g.} ascites, encephalopathy, or variceal bleeding\]), 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 randomization.
• •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. In addition, if heparin is used during pharmacokinetic (PK) sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
• •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 milligram) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• •Corrected QT interval (QTc \[Bazett\]) \>450 milliseconds (msec) or QTc (Bazett) \>480 msec for participants with bundle branch block.
• •Known or suspected active Coronavirus Disease-2019 (COVID-19) infection or has had contact with an individual with known COVID-19, within 14 days of study enrollment.
• •Known or suspected presence of resistance mutations as defined by the International Antiviral Society-United States of America (IAS-USA) resistance guidelines to the individual components of BIK (BIC, FTC, TAF), RPV, and CAB by any historical resistance test result.
• •Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.
• •Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
• •Participant has estimated creatine clearance \<30mL/minute per 1.73 meter square (m\^2) via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.
• •ALT \>=3 times upper limit of normal (ULN).
• •Exposure to an experimental drug or experimental vaccine within either 30 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 Screening:
• •* radiation therapy;
• •* cytotoxic chemotherapeutic agents;
• •* tuberculosis therapy with the exception of 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.
• •Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of study Day 1. Treatment with acyclovir/valacyclovir is permitted.
• •Use of medications which are associated with Torsade de Pointes.
• •Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.