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.