A Phase IIb Study to Evaluate a Long-Acting Intramuscular Regimen for Maintenance of Virologic Suppression (Following Induction With an Oral Regimen of GSK1265744 and Abacavir/Lamivudine) in Human Immunodeficiency Virus Type 1 (HIV-1) Infected, Antiretroviral Therapy-Naive Adult Subjects

Study Overview
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Brief Summary
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This study is a Phase IIb, randomized, multicentre, parallel group, open-label, study having an overall objective to evaluate the antiviral activity, tolerability, and safety of two intramuscular (IM) dosing regimens of GSK744 LA plus TMC278 LA, relative to GSK744 30 milligram (mg) plus Abacavir/Lamivudine (ABC/3TC) given orally once daily (QD), in HIV-1 infected antiretroviral-naïve subjects. GSK744 is the oral formulation of GSK1265744 (cabotegravir), GSK744 LA is the long acting injectable formulation of GSK1265744 and TMC278 LA is the long acting injectable formulation of TMC278. The study will consist of three parts: an Induction Period, Maintenance Period and Extension Period. There is also a Long-Term Follow Up Period for subjects who withdraw from the study and have received at least one dose of GSK744 LA and / or TMC278 LA. In the Induction Period, eligible subjects will receive a combination of an oral regimen of 30 mg of GSK744 and 600/300 mg of ABC/3TC, once daily for 20 weeks. In the Maintenance Period, eligible subjects will be randomized 2:2:1 at Day 1 to receive an IM regimen of GSK744 LA 400 mg + TMC278 LA 600 mg every 4 weeks for 96 weeks (Q4W), an IM regimen of GSK744 LA 600 mg + TMC278 LA 900 mg every 8 weeks for 96 weeks (Q8W), or to continue on the oral Induction Period regimen of GSK744 30 mg + ABC/3TC once daily for 96 weeks (or 104 weeks if continuing on to the Extension Period). The Extension Period will allow for a collection of longer term efficacy and safety and tolerability data from subjects receiving GSK744 LA and TMC278 LA. The study will involve sufficient subjects at screening in order to ensure a total of approximately 265 subjects at the beginning of the Induction Period and approximately 225 subjects randomized into the Maintenance Period.

Official Title
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A Phase IIb Study Evaluating a Long-Acting Intramuscular Regimen of GSK1265744 Plus TMC278 For The Maintenance of Virologic Suppression Following an Induction of Virologic Suppression on an Oral Regimen of GSK1265744 Plus Abacavir/Lamivudine in HIV-1 Infected, Antiretroviral Therapy-Naive Adult Subjects

Conditions
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Infection, Human Immunodeficiency Virus, HIV Infections

Intervention / Treatment
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* Drug: GSK744
* Drug: GSK744 LA
* Drug: TMC278 LA
* Drug: ABC/3TC
* Drug: RPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects screened for this study must be HIV-1 infected and >=18 years of age. A female subject is eligible to enter and participate in the study if she: is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or; is of child-bearing potential with a negative pregnancy test at both Screening and first day of the Induction Period and agrees to use one of the following methods of contraception to avoid pregnancy 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of GSK744 LA and TMC278 LA: Complete abstinence from intercourse (where this is the subject's preferred and usual lifestyle); double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); approved hormonal contraception; any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year; male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject; any other method with published data showing that the lowest expected failure rate is <1% per year; any contraception method must be used consistently and in accordance with the approved product label. All subjects participating in the study must follow safer sexual practices including the use of effective barrier methods (e.g. male condom/spermicide) to minimize risk of HIV transmission. HIV-1 infection as documented by Screening plasma HIV-1 RNA>=1000 c/mL. CD4+ cell count >=200 cells/mm^3 (or higher as local guidelines dictate). ART-naive defined as having no more than 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. French subjects: In France, a subject 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 breastfeeding. Any evidence at screening of an active Center for Disease and Prevention Control (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy. Subjects 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 subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject. Subject who, in the investigator's judgment, poses a significant suicide risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk. The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions. History of ongoing or clinically relevant hepatitis within the previous 6 months, including chronic Hepatitis B virus (HBV) infection (HBsAg positive). 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 such therapy during the randomized portion of the study must be excluded. History of liver cirrhosis with or without hepatitis viral co-infection. Ongoing or clinically relevant pancreatitis. History of the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia. Personal or known family history of prolonged QT syndrome. Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug 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. Any evidence of primary resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result. Any verified Grade 4 laboratory abnormality. 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 creatinine clearance <50 mL/min via Cockcroft-Gault method. Alanine aminotransferase (ALT) >=5 times Upper limit of normal (ULN). Subjects with ALT >2xULN but <5xULN may participate in the study, if in the opinion of the Investigator and GlaxoSmithKline (GSK) medical monitor the lab abnormality will not interfere with the study procedures or compromise subject safety. Alanine aminotransferase (ALT) >=3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin). Any clinically significant finding on screening or Baseline electrocardiograph (ECG), specifically: Heart rate <45 and >100 beats per minute (bpm) (Males) and <50 and >100 bpm (Females) (100 to 110 bpm can be rechecked within 30 minutes to verify eligibility), QRS duration >120 milliseconds (msec), QTc interval (B or F) >450 msec; non-sustained (>=3 consecutive beats) or sustained ventricular tachycardia; sinus pauses >2.5 seconds; 2nd degree (Type II) or higher atrio-ventricular (AV) block; evidence of WPW (Wolff- Parkinson-White) syndrome (ventricular pre-excitation); pathologic Q waves defined as Q wave >40msec OR depth >0.4 mV; any significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator and GSK medical monitor, will interfere with the safety for the individual subject. Subjects who are human leukocyte antigen (HLA)-B*5701 positive and unable to use an alternative nucleoside reverse transcriptase inhibitor (NRTI) backbone (subjects who are HLA-B*5701 positive may be enrolled if they use an alternative NRTI backbone that does not contain abacavir). 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 IP. Treatment with any of the following agents within 28 days of Screening; radiation therapy, cytotoxic chemotherapeutic agents, tuberculosis therapy and Immunomodulators that alter immune responses (such as 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 the first dose of IP.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK744 LA 600 mg + TMC278 LA 900 mg every 8 weeks (Q8W)<br>In the Induction Period of 20 weeks, subjects will receive an oral regimen of GSK744 30 mg once daily plus ABC/3TC 600/300 mg once daily. In the last 4 weeks of the Induction Period subject will also receive RPV 25 mg tablet once daily. In the Maintenance Period, subject will receive following IM doses: Day 1 only - GSK744 LA 800 mg (loading dose delivered as two 400 mg IM injections) + TMC278 LA 900 mg IM. Week 4 only - GSK744 LA 600 mg IM (second loading dose, no TMC278).Week 8 - GSK744 LA 600 mg IM + TMC278 LA 900 mg IM every 8 weeks for 96 weeks. | Drug: GSK744 LA<br>* Sterile white to slightly colored suspension containing 200 mg/mL of GSK744 as free acid (GSK1265744 free acid), polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection, packaged in a 3 mL USP Type I glass vial, for administration by IM injection<br>Drug: TMC278 LA<br>* Sterile white suspension containing 300 mg/mL of TMC278 as free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection, packaged in a 2 mL USP Type I glass vial, for administration by IM injection.<br>Drug: ABC/3TC<br>* ABC/3TC fixed dose combination (FDC) oral tablet, containing 600 mg of ABC (as abacavir sulfate) and 300 mg of 3TC<br>Drug: RPV<br>* Off-white, round, biconvex, film-coated 25 mg Rilpivirine (RPV) tablets for oral administration. Eligible subjects switching from the oral regimen to the IM regimen in the Extension Period will receive 2 weeks of RPV 25 mg once daily, from Week 102 through Week 104<br>|
| Experimental: GSK744 LA 400 mg + TMC278 LA 600 mg every 4 weeks (Q4W)<br>In the Induction Period of 20 weeks, subjects will receive an oral regimen of GSK744 30 mg once daily plus ABC/3TC 600/300 mg once daily. In the last 4 weeks of the Induction Period subjects will also receive RPV 25 mg tablet once daily. In the Maintenance Period, subjects will receive following IM doses: Day 1 only - GSK744 LA 800 mg (loading dose delivered as two 400 mg IM injections) + TMC278 LA 600 mg IM. Week 4 - GSK744 LA 400 mg IM + TMC278 LA 600 mg IM every 4 weeks for 96 weeks | Drug: GSK744 LA<br>* Sterile white to slightly colored suspension containing 200 mg/mL of GSK744 as free acid (GSK1265744 free acid), polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection, packaged in a 3 mL USP Type I glass vial, for administration by IM injection<br>Drug: TMC278 LA<br>* Sterile white suspension containing 300 mg/mL of TMC278 as free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection, packaged in a 2 mL USP Type I glass vial, for administration by IM injection.<br>Drug: ABC/3TC<br>* ABC/3TC fixed dose combination (FDC) oral tablet, containing 600 mg of ABC (as abacavir sulfate) and 300 mg of 3TC<br>Drug: RPV<br>* Off-white, round, biconvex, film-coated 25 mg Rilpivirine (RPV) tablets for oral administration. Eligible subjects switching from the oral regimen to the IM regimen in the Extension Period will receive 2 weeks of RPV 25 mg once daily, from Week 102 through Week 104<br>|
| Active Comparator: Oral Control Arm<br>In the Induction Period of 20 weeks, subjects will receive an oral regimen of GSK744 30 mg once daily plus ABC/3TC 600/300 mg once daily. In the last 4 weeks of the Induction Period subjects will also receive RPV 25 mg tablet once daily. In the Maintenance Period, subjects will receive an oral regimen of 30 mg of GSK744 and ABC/3TC once daily for 96 weeks (or 104 weeks if going on to the Extension Period) | Drug: GSK744<br>* White to almost white oval shaped film coated 30 mg tablets for oral administration.<br>Drug: ABC/3TC<br>* ABC/3TC fixed dose combination (FDC) oral tablet, containing 600 mg of ABC (as abacavir sulfate) and 300 mg of 3TC<br>Drug: RPV<br>* Off-white, round, biconvex, film-coated 25 mg Rilpivirine (RPV) tablets for oral administration. Eligible subjects switching from the oral regimen to the IM regimen in the Extension Period will receive 2 weeks of RPV 25 mg once daily, from Week 102 through Week 104<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Level Below 50 Copies/Milliliter (c/mL) at Week 32 | Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest as non-responders. The Intent-to-Treat Maintenance Exposed (ITT-ME) Population consisted of all randomized participants who received at least one injection or one dose of investigational product during the Maintenance Period of the study (on or after Day 1 visit). | Week 32 | 
| Number of Participants With Protocol Defined Virologic Failure (PDVF) Until Week 32 | Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than 1.0 logarithm to base 10 (log10) c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL. | Up to Week 32 | 
| Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) (Induction Period) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical intervention, drug-induced liver injury with hyperbilirubinaemia. | Up to 20 weeks | 
| Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) (Maintenance Period) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical intervention, drug-induced liver injury with hyperbilirubinaemia. Data presented includes all post-baseline induction period and maintenance period adverse events, as well as long-term follow-up period adverse events for those participants who did not enter the extension period. | Up to an average of 59 weeks | 
| Number of Participants With Post-Baseline Adverse Events by Maximum Toxicity Grade | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with post-Baseline adverse events by maximum toxicity Grade have been presented. | Up to an average of 59 weeks | 
| Number of Participants With Maximum Post-Baseline Emergent Toxicities for Clinical Chemistry Parameters | Clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), carbon dioxide(CO2) content/bicarbonate (HCO3), cholesterol, creatine kinase (CK), glucose, low density lipoprotein (LDL) cholesterol, lipase, potassium, and sodium, total bilirubin (TBIL) and triglycerides were evaluated. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the chemistry parameters have been presented. | Up to an average of 59 weeks | 
| Number of Participants With Maximum Post-Baseline Emergent Toxicities for Hematology Parameters | Hematology parameters hemoglobin, platelet count, total neutrophils and white blood cell count were evaluated. Toxicity was graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the hematology parameters have been presented. | Up to an average of 59 weeks | 
| Number of Participants With Post-Baseline Urinalysis Dipstick Results | Urinalysis dipstick included urine occult blood, urine glucose, urine ketones, urine nitrite, urine protein and urine leukocyte. The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as positive, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample. Data presented includes all post-baseline dipstick results during Induction and Maintenance Periods, as well as LTFP for those participants who did not enter the extension period. | Up to an average of 59 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma HIV-1 RNA <200 c/mL and <50 c/mL, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Percentage of participants with HIV-1 RNA <200 c/mL and <50 c/mL for oral dose of CAB 30 mg plus ABC/3TC during Induction Period was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders. The Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of investigational product. | Week -20, Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Absolute Values of Plasma HIV-1 RNA, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Plasma samples for quantitative HIV-1 RNA were collected at indicated time points. Log10 values for HIV-1 RNA have been presented. | Week -20, Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Plasma HIV-1 RNA, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Plasma samples for quantitative HIV-1 RNA were collected at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as: HIV-1 RNA(log 10) at post-baseline visit minus HIV-1 RNA(log 10) at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Absolute Values of Cluster of Differentiation 4+ (CD4+), for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Blood samples were collected at specified time points to assess CD4+ using flow cytometry. Mean and standard deviation values for CD4+ are presented. | Week -20, Week -16, Week -12, Week -4, Day 1 | 
| Change From Baseline in CD4+, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -4, Day 1 | 
| Number of Participants With AEs by Their Severity Grades, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. | Up to 20 Weeks | 
| Number of Participants With Maximum Post-Baseline Emergent Toxicities for Hematology Parameters, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Hematology parameters hemoglobin, platelet count, total neutrophils and white blood cell count were evaluated. Laboratory toxicities were graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Number of participants with any time post-baseline maximum emergent toxicities in any of the hematology parameters have been presented. | Up to Week 20 | 
| Number of Participants With Maximum Post-Baseline Emergent Toxicities for Clinical Chemistry Parameters, for Oral Dose of CAB 30 mg Plus ABC/3TC (Induction Period) | Clinical chemistry parameters AST, ALT, ALP, CO2/HCO3, cholesterol, CK, glucose, LDL cholesterol, lipase, potassium, and sodium, total TBIL and triglycerides were evaluated. Laboratory toxicities were graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Number of participants with any time post-baseline maximum emergent toxicities in any of the chemistry parameters have been presented. | Up to 20 weeks | 
| Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK (Induction Period) | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Clinical Chemistry Parameter: Albumin (Induction Period) | Blood samples were collected for the analysis of clinical chemistry parameter: Albumin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine (Induction Period) | Blood samples were collected for the analysis of clinical chemistry parameters including total Bilirubin and Creatinine at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Clinical Chemistry Parameters: CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea (Induction Period) | Blood samples were collected for the analysis of clinical chemistry parameters including total CO2, chloride, cholesterol, glucose, potassium, sodium, triglyceride and urea at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Clinical Chemistry Parameter: Lipase (Induction Period) | Blood samples were collected for the analysis of clinical chemistry parameter: Lipase at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Hematology Parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets Count and White Blood Cells (WBC) Count (Induction Period) | Blood samples were collected for the analysis of hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and WBC at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Hematology Parameter: Hematocrit (Induction Period) | Blood samples were collected for the analysis of hematology parameter: Hematocrit at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Hematology Parameter: Hemoglobin (Induction Period) | Blood samples were collected for the analysis of hematology parameter: Hemoglobin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Hematology Parameter: Mean Corpuscle Volume (Induction Period) | Blood samples were collected for the analysis of hematology parameter: Mean Corpuscle Volume at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Change From Baseline in Hematology Parameter: Red Blood Cell Count (Induction Period) | Blood samples were collected for the analysis of hematology parameter: Red Blood Cell count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1 | 
| Percentage of Participants With Plasma HIV-1 RNA Level <50 c/mL and <200 c/mL Over Week 32 (Maintenance Period) | Percentage of participants with HIV-1 RNA <50 c/mL and <200 c/mL was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders. | Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 | 
| Number of Participants With Protocol Defined Virologic Failure at Week 32 (Maintenance Period) | Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL. | Week 32 | 
| Absolute Value of Plasma HIV-1 RNA at Week 32 (Maintenance Period) | Plasma samples for quantitative HIV-1 RNA analysis were collected at indicated time points during Maintenance Period. Log10 values for HIV-1 RNA have been presented. | Week 32 | 
| Change From Baseline in Plasma HIV-1 RNA at Week 32 (Maintenance Period) | Plasma samples for quantitative HIV-1 RNA analysis were collected at indicated time points during Maintenance Period. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as: HIV-1 RNA(log 10) at post-baseline visit minus HIV-1 RNA(log 10) at Baseline. | Baseline (Week -20) and Week 32 | 
| Absolute Value of CD4+ at Week 32 (Maintenance Period) | Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in CD4+ at Week 32 (Maintenance Period) | Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as post-baseline value minus Baseline value. | Baseline (Week -20) and Week 32 | 
| Number of Participants With HIV-1 Disease Progression Over Week 32 (Maintenance Period) | HIV-associated conditions were recorded during the study and was assessed according to the Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. The clinical categories of HIV infection as per CDC system are class A=Asymptomatic HIV infection or lymphadenopathy or acute HIV infection; class B=symptomatic non-acquired immunodeficiency syndrome (AIDS) conditions and class C=AIDS indicator conditions. Number of participants experiencing disease progression is presented, where disease progression is defined as the progression from Baseline HIV disease status as follows: CDC class A at Baseline to CDC class C event; CDC Class B at Baseline to CDC Class C event; CDC Class C at Baseline to new CDC Class C event; and CDC class A, B or C at Baseline to death. | Up to Week 32 | 
| Number of Participants With AEs by Their Severity Grades Over Week 32 (Maintenance Period) | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. | Up to Week 32 | 
| Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Clinical Chemistry Parameter: Albumin at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of clinical chemistry parameters including Albumin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of clinical chemistry parameters including Total Bilirubin and Creatinine at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Clinical Chemistry Parameters: Total CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of clinical chemistry parameters including total CO2, chloride, cholesterol, glucose, potassium, sodium, triglyceride and urea at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Clinical Chemistry Parameter: Lipase at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of clinical chemistry parameters including Lipase at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Hematology Parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelet Count and WBC Count at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of hematology parameters including Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelet count and WBC count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Hematology Parameter: Hematocrit at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of hematology parameters including Hematocrit at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Hematology Parameter: Hemoglobin at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of hematology parameters including Hemoglobin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Hematology Parameter: Mean Corpuscle Volume at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of hematology parameters including Mean Corpuscle Volume at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Change From Baseline in Hematology Parameter: Red Blood Cell Count at Week 32 (Maintenance Period) | Blood samples were collected for the analysis of hematology parameters including Red Blood Cell count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline. | Baseline (Week -20) and Week 32 | 
| Average Initial Concentration (C0) and Maximum Plasma Concentration (Cmax) of CAB LA (Q4W IM and Q8W IM Dosing) (Maintenance Period) | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB LA. The PK Concentration Population included all participants who received CAB LA and/or RPV LA and underwent PK sampling during the study, and provided available CAB LA and/or RPV LA plasma concentration data. | pre-dose and 2 hours post dose on Day 1, pre-dose on Weeks 1,4,8,12,16,20,24,25,28 and 32 | 
| Average Initial Concentration (C0) and Cmax of RPV LA (Q4W IM and Q8W IM Dosing) (Maintenance Period) | Blood samples were collected at indicated time points for PK analysis of RPV LA. C0 and Cmax of RPV LA (Q4W IM and Q8W IM dosing) was evaluated. | pre-dose and 2 hours post dose on Day 1, pre-dose on Weeks 1,4,8,12,16,20,24,25,28 and 32 | 
| Trough Concentration (Ctrough) of CAB LA (Q8W IM Dosing) Used for Assessment of Steady State (Maintenance Period) | Blood samples were collected at indicated time points for PK analysis of CAB LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for CAB LA (Q8W IM dosing) which were considered for the assessment of steady state are presented. | Pre-dose on Weeks 16, 24 and 32 | 
| Ctrough of CAB LA (Q4W IM Dosing) Used for Assessment of Steady State (Maintenance Period) | Blood samples were collected at indicated time points for PK analysis of CAB LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for CAB LA (Q4W IM dosing) which were considered for the assessment of steady state are presented. | Pre-dose on Weeks 16, 20, 24, 28 and 32 | 
| Ctrough of RPV LA (Q8W IM Dosing) Used for Assessment of Steady State (Maintenance Period) | Blood samples were collected at indicated time points for PK analysis of RPV LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for RPV LA (Q8W IM dosing) which were considered for the assessment of steady state are presented. | Pre-dose on Weeks 16, 24 and 32 | 
| Ctrough of RPV LA (Q4W IM Dosing) Used for Assessment of Steady State (Maintenance Period) | Blood samples were collected at indicated time points for PK analysis of RPV LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for RPV LA (Q4W IM dosing) which were considered for the assessment of steady state are presented. | Pre-dose on Weeks 16, 20, 24, 28 and 32 | 
| Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in Relation With PK Parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: area under plasma concentration-time curve from time zero to the end of dosing interval (AUC [0-tau]) of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is HIV-1 RNA<50 c/mL (success) and the independent variable is PK parameter (AUC [0-tau]). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter AUC (0-tau). | Up to Week 32 | 
| Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in Relation With PK Parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: Average C0 of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is HIV-1 RNA<50 c/mL (success) and the independent variable is PK parameter (Average C0). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Average C0. | Up to Week 32 | 
| Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in Relation With PK Parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: Cmax of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is HIV-1 RNA<50 c/mL (success) and the independent variable is PK parameter (Cmax). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Cmax. | Up to Week 32 | 
| Virologic Failure (From MSDF Algorithm) in Relation With PK Parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: AUC (0-tau) of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is virologic failure and the independent variable is PK parameter (AUC [0-tau]). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter AUC (0-tau). | Up to Week 32 | 
| Virologic Failure (From MSDF Algorithm) in Relation With PK Parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: Average C0 of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is virologic failure and the independent variable is PK parameter (Average C0). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Average C0. | Up to Week 32 | 
| Virologic Failure (From MSDF Algorithm) in Relation With PK Parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period) | Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: Cmax of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is virologic failure and the independent variable is PK parameter (Cmax). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Cmax. | Up to Week 32 | 
| Number of Participants With Treatment-emergent Genotypic Resistance | Plasma samples were collected to assess treatment emergent Genotypic Resistance for participants who had confirmed virologic failure. Number of participants who had any Integrase Inhibitor (INI) mutations or major mutations of other classes (Nucleoside reverse transcriptase inhibitor [NRTI], Non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI])are presented. | Up to Week 32 | 
| Number of Participants With Treatment-emergent Phenotypic Resistance | Plasma samples were collected for drug resistance testing. Number of participants, with treatment emergent phenotypic resistance to INI, NNRTI, NRTI and/or PI were summarized. Overall susceptibility of the drug was categorized as sensitive, partially sensitive and resistant. | Up to Week 32 | 
| Percentage of Participants With Plasma HIV-1 RNA Level <50 c/mL Over Week 32 by Subgroups (Maintenance Period) | Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders. Data is presented for following subgroups: Baseline plasma HIV-1 RNA levels, Baseline CD4+ cell count, Race and HIV Risk factor (Homosexual contact [HC] and not injectable drug user). | Up to Week 32 | 
| Percentage of Participants With Protocol Defined Virologic Failure (PDVF) at Week 32 by Subgroups(Maintenance Period) | Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL. Data is presented for following subgroups: Baseline plasma HIV-1 RNA levels, Baseline CD4+ cell count, Race and HIV Risk factor (Homosexual contact [HC] and not injectable drug user). | Up to Week 32 | 
| HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQ[s]) Total Score at Week 32 (Maintenance Period) | The HIVTSQ(s) was developed to evaluate treatments for HIV and participant satisfaction. It has total 14 items and each items are scored from 6 (very satisfied) to 0 (very dissatisfied). Items 1 to 12 are summed to produce the Total Treatment Satisfaction Score with a possible range of 0 to 72. Higher scores represent greater treatment satisfaction as compared to the past few weeks. | Week 32 | 
| HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQ[c]) Total Score at Week 32 (Maintenance Period) | The HIVTSQ(c) was developed to evaluate treatments for HIV and participant satisfaction. It has total 14 items and each items are scored from +3 ('much more satisfied', 'much more convenient', 'much more flexible', etc.) to -3 ('much less satisfied', 'much less convenient', 'much less flexible', etc.). Items 1 to 12 (excluding Items 7b and 9b) are summed to produce a Total Treatment Satisfaction Score (change) with a possible range of -33 to +33. The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. | Week 32 | 
| Number of Participants With HIV Medication Questionnaire (HIVMQ) Item E and F Scores at Week 32 (Maintenance Period) | The HIVMQ was developed to assess participant reported medication adherence. It has 6 items (a, b, c, d, e, f). Item E (How often do you find it inconvenient or difficult to take/receive medication as recommended?) and Item F (How much pain/discomfort have experienced with this medication?). Each of these 2 items are scored from 0 (none of the time) to 6 (all of the time). The higher the score, the greater the adherence to medication. Number of participants with HIVMQ Item E and F Scores at Week 32 by their score categories (0: none of the time to 6: all of the time) are presented. | Week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adherence, induction, treatment satisfication, TMC278, bi-monthly, GSK744, injectable, long acting, maintenance, abacavir, every other month, rilpivirine, HIV-1 infection, integrase inhibitor, TMC278 LA, RPV, non-nucleoside reverse transcriptase inhibitor, LA, once monthly, GSK1265744, once daily, lamivudine, therapy-naive