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

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.

Plasma samples for quantitative HIV-1 RNA were collected at indicated time points. Log10 values for HIV-1 RNA have been presented.

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.

Blood samples were collected at specified time points to assess CD4+ using flow cytometry. Mean and standard deviation values for CD4+ are presented.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. SD=0.000 is defined as following: if participants analyzed at a specific timepoint have resulted same values, then SD is considered equal with 0.000.

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.

Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Standard Error (SE)=0.000 is defined as following: if for all participants was resulted same value for the specific timepoint, then SE is equal with 0.000 .

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.

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.

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).

SE=0.000 is defined as following: if for all participants was resulted same value for the specific timepoint, then SE is equal with 0.000.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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 96 by their score categories (0: none of the time to 6: all of the time) are presented.