Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants

Inclusion Criteria: - HIV-1 infected, ART-naive men or women aged 18 years or greater at
the time of signing the informed consent. - HIV-1 infection as documented by Screening
plasma HIV-1 RNA >=1000 c/mL; - Antiretroviral-naive (<=10 days of prior therapy with any
antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an
HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be
exclusionary. - Female Participants: A female participant is eligible to participate if she
is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative
serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the
following conditions applies: 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. 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. The investigator is responsible for ensuring that participants understand how to
properly use these methods of contraception. All participants in the study should be
counseled 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. -
Capable of giving signed informed consent which includes compliance with the requirements
and restrictions listed in the consent form and in this protocol. - 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: - Women who are pregnant, breastfeeding, or plan to become pregnant or
breastfeed during the study. - Any evidence at Screening of an active Centers for Disease
and Prevention Control (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not
requiring systemic therapy or historic or current cluster of differentiation4+ (CD4+) cell
count <200 cells/ cubic millimeter (mm^3) are not exclusionary. - Participants with known
moderate to severe hepatic impairment. - Any pre-existing physical or mental condition
(including substance abuse 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. All cases of prior seizure history should be discussed with the Medical
Monitor prior to enrolment. - Participant who, in the investigator's judgment, poses 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 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 dioxyribose nucleic 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. Note: Participants positive for anti-HBc
(negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune
to HBV and are not 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 are anticipated to require
HCV treatment prior to Week 48 of the Maintenance Phase must be excluded. HCV treatment on
study may be permitted post Week 48, following consultation with the Medical Monitor.
Participants 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, HCV is not
advanced, and will not require treatment prior to the Week 48 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. In the event that recent biopsy or imaging data is not available or is
inconclusive, the Fib-4 score will be used to verify eligibility. A 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 [square root of ALT]). - Unstable liver disease (as
defined by any of the following: presence of ascites, encephalopathy, coagulopathy,
hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), 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. - All participants will be screened for syphilis (rapid plasma reagin [RPR]).
Participants with untreated syphilis infection, defined as a positive RPR without clear
documentation of treatment, are excluded. Participants with a positive RPR test who have
not been treated may be rescreened at least 30 days after completion of antibiotic
treatment for syphilis. - Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal
cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical,
anal or penile intraepithelial neoplasia; other localized malignancies require agreement
between the investigator and the study Medical Monitor for inclusion of the participant
prior to enrollment. - Any condition which, in the opinion of the Investigator, may
interfere with the absorption, distribution, metabolism or excretion of the drug 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 sampling (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. - Alanine aminotransferase (ALT)
>=3 times upper limit normal (ULN). - 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. -
Exposure to an experimental drug and/or experimental vaccine within 28 days or 5 half-lives
of the test agent, or twice the duration of the biological effect of the test agent,
whichever is longer, prior to the first dose of investigational product (IP). - Treatment
with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic
chemotherapeutic agents; tuberculosis (TB) therapy, with the exception of treatment of
latent TB with isoniazid; Immunomodulators that alter immune responses (such as chronic
systemic corticosteroids, interleukins, or interferons). Note: Participants using
short-term (e.g. =<21 day) systemic corticosteroid treatment, topical, inhaled or
intranasal corticosteroids are eligible for enrollment. - 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
the first dose of IP. - Use of medications which are associated with Torsades de Pointes -
Any evidence of primary resistance to non-nuclease reverse transcriptase inhibitors
(NNRTIs) (except for K103N which is allowed), or any known resistance to INIs from
historical resistance test results. Note: re-tests of Screening genotypes are allowed only
at the discretion of the study virologist. - Participants who are HLA-B*5701 positive and
are unable to use an nuclease reverse transcriptase inhibitors (NRTI) backbone that does
not contain abacavir (participants who are HLA-B*5701 positive may be enrolled if they use
a NRTI backbone that does not contain abacavir; HLA-B*5701 positive participants may be
excluded from the study if local provision of an alternate NRTI backbone is not possible).
- 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 creatinine clearance <50
mL/min/1.73m^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation. - Participants who are currently participating in or anticipate to be selected
for any other interventional study.