Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults

Inclusion Criteria: * Aged 18 years or older (or ≥19 where required by local regulatory agencies), at the time of signing the informed consent. * Must be on uninterrupted current regimen (either the initial or second ARV 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 ≥400 c/mL). * Acceptable stable (initial or second) ARV regimens prior to Screening include 2 NRTIs plus: INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen);NNRTI (either the initial or second cART regimen);Boosted PI (or atazanavir \[ATV\] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability) The addition, removal, or switch of a drug(s) that has been used to treat HIV based on antiretroviral properties of the drug constitutes a change in ART with the following limited exceptions: Historical changes in formulations of ART drugs or booster drugs will not constitute a change in ART regimen if the data support similar exposures and efficacy, and the change must have been at least 3 months prior to Screening; Historical perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen; A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy. * Documented evidence of at least two plasma HIV-1 RNA measurements \<50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening; * Plasma HIV-1 RNA \<50 c/mL at Screening; * A female subjects is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential 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 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, and until 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. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form. Eligible subjects 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 subjects 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. * Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category. * All subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner. Exclusion Criteria: * Within 6 months prior to Screening and after confirmed suppression to \<50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement ≥50 c/mL * Within the 6 to 12 month window prior to Screening and after confirmed suppression to \<50 c/mL, any plasma HIV-1 RNA measurement \>200 c/mL, or 2 or more plasma HIV-1 RNA measurements ≥50 c/mL * Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns * Any switch 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 ≥400 c/mL after initial suppression to \<50 c/mL while on first line HIV therapy regimen) * Abacavir/dolutegravir/lamivudine, (ABC/DTG/3TC) as current ART regimen * A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART * Subjects who are currently participating in or anticipate to be selected for any other interventional study * Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study * Any evidence of an active 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 CD4 cell counts less than 200 cells/mm\^3 * Subjects 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 subjects ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject. * Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrolment 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 enrolment * All subjects will be screened for syphilis (rapid plasma reagin \[RPR\]). Subjects with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Subjects with a serofast RPR result (persistence of a reactive nontreponemal syphilis test) despite history of adequate therapy and no evidence of re-exposure may enrol after consultation with the Medical Monitor. Subjects with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis * Subjects who, in the investigator's judgment, pose a significant suicide risk. Subject's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk * The subject has a tattoo 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 DNA as follows:•Subjects positive for HBsAg are excluded; * Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and 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; subjects who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted post Week 48, following consultation with the medical monitor) Subjects with HCV co-infection will be allowed entry into phase 3 studies if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Week 48 visit. Additional information (where available) on subjects 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. 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 \> 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 subject 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 subject 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 PK sampling, subjects 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 (≤325mg). * Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International AIDS Society \[IAS\]-USA, 2015) 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 subject's participation in the study of an investigational compound * Subject has estimated creatine clearance \<50mL/min per 1.73m\^2 via CKDEPI Method * Alanine aminotransferase (ALT) ≥3 × 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. Note: Subjects using short term (e.g. ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment. * 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 * Use of medications which are associated with Torsade de Pointes. * Current or prior history of etravirine (ETR) * Current use of tipranavir/ritonavir or fosamprenavir/ritonavir * Subjects receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.