A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 631
- 试验地点
- 109
- 主要终点
- Percentage of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48
研究概览
简要总结
The First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, anti-retroviral therapy (ART)-naïve adult participants. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B*5701 positive at Screening may enroll into the study and receive DTG plus a non-abacavir containing dual nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day 1). Participants who have an HIV 1 ribose nucleic acid (RNA) <50 copies per milliliter (c/mL) at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from visit Week 4b until study completion or withdrawal. Participants who successfully complete Week 100 (without meeting study defined withdrawal criteria and who remain virologically suppressed through Week 96: HIV-1 RNA <50 c/mL) will be given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study. Participants will continue to receive injections every 4 weeks during the Extension Phase until CAB LA and RPV LA are either locally approved and commercially available, the participant no longer derives clinical benefit, the participant meets a protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA is terminated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
CAB LA + RPV LA every 4 weeks
After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.
干预措施: Rilpivirine - Injectable Suspension (RPV LA) (Drug)
ABC / DTG / 3TC (600 mg/50mg/300mg) once daily
After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily).
干预措施: ABC/DTG/3TC STR - Tablet (Drug)
ABC / DTG / 3TC (600 mg/50mg/300mg) once daily
After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily).
干预措施: DTG Tablet (Drug)
CAB LA + RPV LA every 4 weeks
After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.
干预措施: Rilpivirine (RPV) tablet (Drug)
CAB LA + RPV LA every 4 weeks
After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.
干预措施: Cabotegravir - Injectable Suspension (CAB LA) (Drug)
CAB LA + RPV LA every 4 weeks
After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.
干预措施: Cabotegravir (CAB) tablet (Drug)
结局指标
主要结局
Percentage of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48
时间窗: Week 48
Percentage of participants with virologic failure endpoint (HIV-1 RNA\>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the noninferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC regimen over 48 weeks in HIV-1 infected ARTexperienced participants. The HIV-1 RNA \>=50 copies/mL per snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window (+/- 6 weeks) or at time of discontinuation (if discontinuation occurred prior to Week 48 for reasons other than Adverse Event).
次要结局
- Percentage of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48(Week 48)
- Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48(Week 48)
- Number of Participants With Confirmed Virologic Failure (CVF) During the Maintenance Phase(Week 48)
- Absolute Values for Plasma HIV-1 RNA at Week 48(Week 48)
- Change From Baseline Values for Plasma HIV-1 RNA at Week 48(Baseline (Day 1) and at Week 48)
- Absolute Values for CD4+ Lymphocyte Count at Week 48(Week 48)
- Number of Participants With Disease Progression(Day 1 up to an average of 59 weeks)
- Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)(Day 1 up to an average of 59 Weeks)
- Absolute Values for Hematology Parameters Over Time Including Week 48: Hematocrit(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for CD4+ Lymphocyte Count at Week 48(Baseline (Day 1) and Week 48)
- Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocytes(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Number of Participants With Severity of Adverse Events(Up to Week 48)
- Absolute Values for Hematology Parameters Over Time Including Week 48: Basophils, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocyte Mean Corpuscular Volume(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Hematology Parameters Over Time Including Week 48: Hemoglobin(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Number of Participants With Abnormal Urinalysis Parameter Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Absolute Values for Fasting Lipid Panel Overtime Including Week 48(Baseline (Day 1) and at Week 48)
- Change From Baseline for Hematology Parameters: Hematocrit(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Fasting Lipid Panel and Glucose Overtime Including Week 48(Baseline (Day 1) and at Week 48)
- Area Under the Curve (AUC) for CAB LA(Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48)
- Change From Baseline for Hematology Parameters: Erythrocytes(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline for Hematology Parameters: Hemoglobin(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance(Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48(Baseline (Day 1) and at Week 48)
- AUC for RPV LA(Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48)
- Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire(Baseline (Day 1) and at Weeks 24 and 48)
- Change From Baseline in HIV Medication, MEDWO Using HATQoL(Baseline and at Weeks 24 and 48)
- Change From Baseline in DISWO Using HATQoL(Baseline and at Weeks 24 and 48)
- Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Change From Baseline Values in Urine Creatinine Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48(Baseline (Day 1) and at Week 48)
- Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Change From Baseline Values in Urine pH Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48(Up to Week 48)
- Number of Participants With Phenotypic Resistance Through Week 48(Week 48)
- Number of Participants With Genotypic Resistance Through Week 48(Week 48)
- Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41(Week 41- 1 Week post dose)
- Cmax in Plasma for RPV LA Evaluable at Week 41(Week 41- 1 Week post dose)
- Change From Baseline Values in Urine Phosphate Over Time Including Week 48(Baseline (Day 1) and at Weeks 4, 24 and 48)
- Plasma Trough Concentration (Ctrough) for CAB LA Evaluable(Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Ctrough for RPV LA Evaluable(Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48)
- Change From Week 5 in Dimension Scores Using Perception of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF)(Weeks 5 and at Weeks 41 and 48)
- Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire(Weeks 5, 41 and 48)
- Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)(Baseline and at Weeks 24 and 48)
- Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44(Baseline and at Weeks 4b, 24 and 44)
- Change in Treatment Satisfaction Over Time Using HIVTSQc at Week 48(Week 48)
- Change From Baseline in Individual Item Scores of HIVTSQs at Weeks 4b, 24 and 44(Baseline and at Weeks 4b, 24 and 44)
- Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire(Baseline and at Weeks 8, 24 and 48)
- Change From 4b in Tolerability of Injection at Weeks 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm(Weeks 4b, 5, 40 and 41)