Infection, Human Immunodeficiency Virus I
Conditions
Keywords
integrase inhibitor, HIV Infection, raltegravir, GSK1349572
Brief summary
The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50 mg once daily versus RAL 400mg twice daily over 48 weeks; non-inferiority will also be tested at Week 96. Both GSK1349572 and RAL will be given in combination with fixed-dose dual NRTI therapy (ABC/3TC or TDF/FTC). This study will be conducted in HIV-1 infected ART-naïve adult subjects.
Detailed description
ING113086 is a Phase 3 randomized, double-blind, double dummy, active-controlled, multicenter, study conducted in approximately 788 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 one of the following treatment arms: 1. GSK1349572 50 mg once daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC) OR 2. 400 mg RAL twice daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC) Analyses will be conducted at 48 weeks and 96 weeks. Subjects randomized to receive GSK1349572 and who successfully complete 96 weeks of treatment will continue to have access to GSK1349572 through the study until either it is locally available, as long as they continue to derive clinical benefit. ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Interventions
GSK1349572 50 mg taken once daily with or without food
DRUGraltegravir
raltegravir 400mg taken twice daily
OTHERGSK1349572 Placebo
GSK1349572 placebo taken once daily
OTHERABC/3TC
Abacavir/Lamivudine background therapy once daily
OTHERTDF/FTC
Tenofovir/emtricitabine background therapy once daily
OTHERraltegravir Placebo
raltegravir placebo taken twice daily
Sponsors
Shionogi
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Screening plasma HIV-1 RNA ≥1000 c/mL * Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) * Ability to understand and sign a written informed consent form * Willingness to use approved methods of contraception to avoid pregnancy (women of child bearing potential only) * Age equal to or greater than 18 years
Exclusion criteria
* Women who are pregnant or breastfeeding; * Active Center for Disease and Prevention Control (CDC) Category C disease * Moderate to severe hepatic impairment * Anticipated need for HCV therapy during the study * Allergy or intolerance to the study drugs or their components or drugs of their class * Malignancy within the past 5 years * Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening * Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening * Exposure to an agent with documented activity against HIV-1 in vitro or an experimental vaccine or drug within 28 days of first dose of study medication * Primary viral resistance in the Screening result * Verified Grade 4 laboratory abnormality * ALT \>5 xULN * ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with \>35% direct bilirubin); * Estimated creatinine clearance \<50 mL/min * Recent history (≤3 months) of upper or lower gastrointestinal bleed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48 | Baseline up to Week 48 | Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 48 and Week 96 | Number of participants with detectable virus that has genotypic or phenotypic evidence of Integrase Inhibitor (INI) resistance were assessed at Week 48 and Week 96. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the deoxyribonucleic acid (DNA) of the host cell. |
| Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 96 | The number of participants with plasma HIV-1 RNA level \<50 c/mL was assessed at Week 96. |
| Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 and Week 96 | The number of participants with plasma HIV-1 RNA level \<400 c/mL was assessed at Week 48 and Week 96. |
| Change From Baseline in Plasma HIV-1 RNA Over Time | Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96 | Change from Baseline in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as the measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). |
| Absolute Values in Plasma HIV-1 RNA Over Time | Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96 | Absolute values in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). |
| Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96 | CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the participants disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start ART. Changes from Baseline in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). |
| Absolute Values in CD4+ Cell Counts Over Time | Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96 | CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy absolute values in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). |
| Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | From Baseline until Week 96 | Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline to a CDC CAT C event (EV); CDC CAT B at Baseline to a CDC CAT C EV; CDC CAT C at Baseline to a new CDC CAT C EV; or CDC CAT A, B, or C at Baseline to death. |
| Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | From Baseline until Week 96 | All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Safety Population: all participants who received at least one dose of investigational product |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG | Week 4, Week 24, and Week 48 | AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. The predicted individual AUC(0-tau) were obtained from the final population PK model by an empirical Bayes estimation. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hours post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. The Pharmacokinetic (PK) Concentration Population comprised of all participants who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data. |
| Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG | Week 4, Week 24, and Week 48 | The maximum plasma concentration (Cmax) and concentration at the end of a dosing interval (Ctau) of DTG were assessed at Week 48. The predicted individual Cmax and Ctau were obtained from the final population PK model by simulation of the concentration-time profiles. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hour post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. |
Countries
Australia, Canada, France, Germany, Italy, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a randomized, parallel group, non-inferiority study to demonstrate the antiviral activity of Dolutegravir. Participants were enrolled from 9 countries. Participants in Dolutegravir arm who completed 96 Weeks double-blind phase continued to receive Dolutegravir in open-label phase, until dolutegravir was locally available commercially.
Pre-assignment details
Total 1035 participants were screened; 827 participants were randomized, and 822 participants entered the treatment period. Of the 5 participants who were randomized but not treated with investigational product, 4 withdrew consent and 1 was randomized in error. 338 participants were enrolled in open label phase to receive Dolutegravir.
Participants by arm
| Arm | Count |
|---|---|
| DTG 50 mg Once a Day Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF)/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study. | 411 |
| RTG 400 mg BID Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. | 411 |
| Total | 822 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Phase: 96 Weeks Duration | Adverse Event | 12 | 7 | 0 |
| Double-blind Phase: 96 Weeks Duration | Lack of Efficacy | 22 | 25 | 0 |
| Double-blind Phase: 96 Weeks Duration | Lost to Follow-up | 22 | 10 | 0 |
| Double-blind Phase: 96 Weeks Duration | Met Protocol-defined Stopping Criteria | 6 | 3 | 0 |
| Double-blind Phase: 96 Weeks Duration | Physician Decision | 3 | 0 | 0 |
| Double-blind Phase: 96 Weeks Duration | Protocol Violation | 18 | 16 | 0 |
| Double-blind Phase: 96 Weeks Duration | Study Closed/Terminated | 6 | 4 | 0 |
| Double-blind Phase: 96 Weeks Duration | Withdrawal by Subject | 18 | 14 | 0 |
| Open-label Phase: Median of 1267 Days | Adverse Event | 0 | 0 | 4 |
| Open-label Phase: Median of 1267 Days | Lack of Efficacy | 0 | 0 | 5 |
| Open-label Phase: Median of 1267 Days | Lost to Follow-up | 0 | 0 | 15 |
| Open-label Phase: Median of 1267 Days | Met Protocol-defined Stopping Criteria | 0 | 0 | 4 |
| Open-label Phase: Median of 1267 Days | Physician Decision | 0 | 0 | 3 |
| Open-label Phase: Median of 1267 Days | Protocol Violation | 0 | 0 | 5 |
| Open-label Phase: Median of 1267 Days | Withdrawal by Subject | 0 | 0 | 8 |
Baseline characteristics
| Characteristic | RTG 400 mg BID | Total | DTG 50 mg Once a Day |
|---|---|---|---|
| Age, Continuous | 36.6 Years STANDARD_DEVIATION 10.02 | 37.0 Years STANDARD_DEVIATION 9.61 | 37.3 Years STANDARD_DEVIATION 9.19 |
| Race/Ethnicity, Customized African American/African Her and Asian and White | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized African American/African Heritage (Her) | 39 Participants | 88 Participants | 49 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 9 Participants | 16 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian and White | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Central/South Asian Her | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Japanese/East Asian Her/South East Asian Her | 10 Participants | 14 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 352 Participants | 698 Participants | 346 Participants |
| Sex: Female, Male Female | 56 Participants | 119 Participants | 63 Participants |
| Sex: Female, Male Male | 355 Participants | 703 Participants | 348 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 411 | 1 / 411 | 0 / 338 |
| other Total, other adverse events | 353 / 411 | 344 / 411 | 256 / 338 |
| serious Total, serious adverse events | 41 / 411 | 45 / 411 | 21 / 338 |
Outcome results
Primary
Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication.
Time frame: Baseline up to Week 48
Population: ITT-E Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg Once a Day | Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48 | 88 Percentage of participants |
| RTG 400 mg BID | Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48 | 85 Percentage of participants |
95% CI: [-2.2, 7.1]
Secondary
Absolute Values in CD4+ Cell Counts Over Time
CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy absolute values in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles).
Time frame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Population: ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 32, n=384, 375 | 606.5 cells/mm^3 | Standard Deviation 242.95 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 12, n=392, 397 | 513.3 cells/mm^3 | Standard Deviation 218.75 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 40, n=371, 357 | 609.1 cells/mm^3 | Standard Deviation 239.11 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Baseline n=411, 411 | 379.2 cells/mm^3 | Standard Deviation 172.32 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 48, n=374, 357 | 623.8 cells/mm^3 | Standard Deviation 247.82 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 60, n=367, 355 | 635.6 cells/mm^3 | Standard Deviation 241.27 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 16, n=394, 392 | 536.4 cells/mm^3 | Standard Deviation 219.47 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 72, n=360, 350 | 635.2 cells/mm^3 | Standard Deviation 237.78 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 8, n=398, 402 | 502.3 cells/mm^3 | Standard Deviation 205.15 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 84, n=351, 338 | 668.0 cells/mm^3 | Standard Deviation 246.5 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 24, n=392, 389 | 582.0 cells/mm^3 | Standard Deviation 232.93 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 96, n=343, 328 | 679.8 cells/mm^3 | Standard Deviation 257.89 |
| DTG 50 mg Once a Day | Absolute Values in CD4+ Cell Counts Over Time | Week 4, n=398, 403 | 474.2 cells/mm^3 | Standard Deviation 199.06 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 96, n=343, 328 | 672.4 cells/mm^3 | Standard Deviation 237.54 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Baseline n=411, 411 | 374.3 cells/mm^3 | Standard Deviation 163.37 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 4, n=398, 403 | 471.8 cells/mm^3 | Standard Deviation 191.02 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 8, n=398, 402 | 502.4 cells/mm^3 | Standard Deviation 187.99 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 12, n=392, 397 | 518.3 cells/mm^3 | Standard Deviation 195.59 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 16, n=394, 392 | 550.1 cells/mm^3 | Standard Deviation 221.77 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 24, n=392, 389 | 580.8 cells/mm^3 | Standard Deviation 218.76 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 32, n=384, 375 | 618.7 cells/mm^3 | Standard Deviation 237.56 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 40, n=371, 357 | 623.1 cells/mm^3 | Standard Deviation 234.82 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 60, n=367, 355 | 648.5 cells/mm^3 | Standard Deviation 238.99 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 72, n=360, 350 | 664.0 cells/mm^3 | Standard Deviation 239.86 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 84, n=351, 338 | 677.5 cells/mm^3 | Standard Deviation 249.64 |
| RTG 400 mg BID | Absolute Values in CD4+ Cell Counts Over Time | Week 48, n=374, 357 | 641.2 cells/mm^3 | Standard Deviation 241.75 |
Secondary
Absolute Values in Plasma HIV-1 RNA Over Time
Absolute values in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles).
Time frame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Population: ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 8, n=397, 402 | 1.646 log10 c/mL | Standard Deviation 0.2006 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 40, n=375, 358 | 1.603 log10 c/mL | Standard Deviation 0.0821 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 16, n=395, 388 | 1.620 log10 c/mL | Standard Deviation 0.1252 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 48, n=374, 358 | 1.606 log10 c/mL | Standard Deviation 0.0866 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 4, n=402, 406 | 1.718 log10 c/mL | Standard Deviation 0.2593 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 60, n=366, 355 | 1.605 log10 c/mL | Standard Deviation 0.1134 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 24, n=393, 390 | 1.643 log10 c/mL | Standard Deviation 0.295 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 72, n=361, 350 | 1.601 log10 c/mL | Standard Deviation 0.0803 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 12, n=396, 395 | 1.626 log10 c/mL | Standard Deviation 0.1323 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 84, n=352, 338 | 1.607 log10 c/mL | Standard Deviation 0.1337 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 32, n=386, 377 | 1.620 log10 c/mL | Standard Deviation 0.1917 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Week 96, n=342, 329 | 1.599 log10 c/mL | Standard Deviation 0.83 |
| DTG 50 mg Once a Day | Absolute Values in Plasma HIV-1 RNA Over Time | Baseline n=411, 411 | 4.538 log10 c/mL | Standard Deviation 0.7258 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 96, n=342, 329 | 1.630 log10 c/mL | Standard Deviation 0.2515 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Baseline n=411, 411 | 4.599 log10 c/mL | Standard Deviation 0.7048 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 4, n=402, 406 | 1.800 log10 c/mL | Standard Deviation 0.4095 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 8, n=397, 402 | 1.709 log10 c/mL | Standard Deviation 0.3791 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 12, n=396, 395 | 1.672 log10 c/mL | Standard Deviation 0.3125 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 16, n=395, 388 | 1.648 log10 c/mL | Standard Deviation 0.2647 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 24, n=393, 390 | 1.655 log10 c/mL | Standard Deviation 0.3476 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 32, n=386, 377 | 1.636 log10 c/mL | Standard Deviation 0.2721 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 40, n=375, 358 | 1.601 log10 c/mL | Standard Deviation 0.0784 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 48, n=374, 358 | 1.599 log10 c/mL | Standard Deviation 0.0582 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 60, n=366, 355 | 1.599 log10 c/mL | Standard Deviation 0.056 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 72, n=361, 350 | 1.605 log10 c/mL | Standard Deviation 0.0836 |
| RTG 400 mg BID | Absolute Values in Plasma HIV-1 RNA Over Time | Week 84, n=352, 338 | 1.614 log10 c/mL | Standard Deviation 0.1279 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG
AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. The predicted individual AUC(0-tau) were obtained from the final population PK model by an empirical Bayes estimation. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hours post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. The Pharmacokinetic (PK) Concentration Population comprised of all participants who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.
Time frame: Week 4, Week 24, and Week 48
Population: PK Concentration Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DTG 50 mg Once a Day | Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG | 53.6 Micrograms*hour per milliliter(µg*hr/mL) | Geometric Coefficient of Variation 26.8 |
Secondary
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time
CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the participants disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start ART. Changes from Baseline in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles).
Time frame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Population: ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 8, n=398, 402 | 121.6 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 127.97 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 40, n=371, 357 | 224.1 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 173.59 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 16, n=394, 392 | 155.1 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 137.23 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 48, n=374, 357 | 238.9 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 171.81 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 4, n=398, 403 | 93.3 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 116.27 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 60, n=367, 355 | 247.8 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 184.11 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 24, n=392, 389 | 199.3 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 161.23 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 72, n=360, 350 | 247.8 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 168.37 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 12, n=392, 397 | 130.7 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 131.49 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 84, n=351, 338 | 281.3 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 175.07 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 32, n=384, 375 | 223.4 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 165.3 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 96, n=343, 328 | 292.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 195.7 |
| DTG 50 mg Once a Day | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Baseline n=411, 411 | 379.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 178.32 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 96, n=343, 328 | 286.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 192.45 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Baseline n=411, 411 | 374.3 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 163.37 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 4, n=398, 403 | 97.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 129.35 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 8, n=398, 402 | 126.6 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 134.59 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 12, n=392, 397 | 145.1 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 144.08 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 16, n=394, 392 | 173.0 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 159.1 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 24, n=392, 389 | 204.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 162.28 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 32, n=384, 375 | 241.3 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 167.64 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 40, n=371, 357 | 239.8 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 173.33 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 48, n=374, 357 | 257.5 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 178.69 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 60, n=367, 355 | 264.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 188.63 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 72, n=360, 350 | 278.6 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 182.76 |
| RTG 400 mg BID | Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time | Week 84, n=351, 338 | 292.9 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 199.42 |
Secondary
Change From Baseline in Plasma HIV-1 RNA Over Time
Change from Baseline in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as the measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles).
Time frame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Population: ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 8, n=397, 402 | -2.897 log10 c/mL | Standard Deviation 0.6837 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 40, n=375, 358 | -2.920 log10 c/mL | Standard Deviation 0.7219 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 16, n=395, 388 | -2.917 log10 c/mL | Standard Deviation 0.6949 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 48, n=374, 358 | -2.915 log10 c/mL | Standard Deviation 0.7237 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 4, n=402, 406 | -2.817 log10 c/mL | Standard Deviation 0.6198 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 60, n=366, 355 | -2.912 log10 c/mL | Standard Deviation 0.7344 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 24, n=393, 390 | -2.896 log10 c/mL | Standard Deviation 0.7889 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 72, n=361, 350 | -2.917 log10 c/mL | Standard Deviation 0.7261 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 12, n=396, 395 | -2.908 log10 c/mL | Standard Deviation 0.6863 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 84, n=352, 338 | -2.932 log10 c/mL | Standard Deviation 0.7073 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 32, n=386, 377 | -2.907 log10 c/mL | Standard Deviation 0.7609 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 96, n=342, 329 | -2.938 log10 c/mL | Standard Deviation 0.7004 |
| DTG 50 mg Once a Day | Change From Baseline in Plasma HIV-1 RNA Over Time | Baseline n=411, 411 | 4.538 log10 c/mL | Standard Deviation 0.7258 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 96, n=342, 329 | -2.901 log10 c/mL | Standard Deviation 0.7072 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Baseline n=411, 411 | 4.599 log10 c/mL | Standard Deviation 0.7048 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 4, n=402, 406 | -2.801 log10 c/mL | Standard Deviation 0.6041 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 8, n=397, 402 | -2.886 log10 c/mL | Standard Deviation 0.6754 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 12, n=396, 395 | -2.918 log10 c/mL | Standard Deviation 0.6834 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 16, n=395, 388 | -2.943 log10 c/mL | Standard Deviation 0.6841 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 24, n=393, 390 | -2.933 log10 c/mL | Standard Deviation 0.7398 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 32, n=386, 377 | -2.947 log10 c/mL | Standard Deviation 0.7613 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 40, n=375, 358 | -2.946 log10 c/mL | Standard Deviation 0.67 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 48, n=374, 358 | -2.942 log10 c/mL | Standard Deviation 0.6737 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 60, n=366, 355 | -2.937 log10 c/mL | Standard Deviation 0.6685 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 72, n=361, 350 | -2.932 log10 c/mL | Standard Deviation 0.6728 |
| RTG 400 mg BID | Change From Baseline in Plasma HIV-1 RNA Over Time | Week 84, n=352, 338 | -2.916 log10 c/mL | Standard Deviation 0.6646 |
Secondary
Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG
The maximum plasma concentration (Cmax) and concentration at the end of a dosing interval (Ctau) of DTG were assessed at Week 48. The predicted individual Cmax and Ctau were obtained from the final population PK model by simulation of the concentration-time profiles. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hour post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa.
Time frame: Week 4, Week 24, and Week 48
Population: PK Concentration Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg Once a Day | Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG | Cmax | 3.69 Micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 19.6 |
| DTG 50 mg Once a Day | Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG | Ctau | 1.10 Micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 46.5 |
Secondary
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.
Number of participants with detectable virus that has genotypic or phenotypic evidence of Integrase Inhibitor (INI) resistance were assessed at Week 48 and Week 96. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the deoxyribonucleic acid (DNA) of the host cell.
Time frame: Week 48 and Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 50 mg Once a Day | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 48, genotypic | 0 Participants |
| DTG 50 mg Once a Day | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 48, phenotypic | 1 Participants |
| DTG 50 mg Once a Day | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 96, genotypic | 0 Participants |
| DTG 50 mg Once a Day | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 96, phenotypic | 1 Participants |
| RTG 400 mg BID | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 96, phenotypic | 2 Participants |
| RTG 400 mg BID | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 48, genotypic | 1 Participants |
| RTG 400 mg BID | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 96, genotypic | 1 Participants |
| RTG 400 mg BID | Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. | Week 48, phenotypic | 2 Participants |
Secondary
Number of Participants With Plasma HIV-1 RNA <400 c/mL
The number of participants with plasma HIV-1 RNA level \<400 c/mL was assessed at Week 48 and Week 96.
Time frame: Week 48 and Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 50 mg Once a Day | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 369 Participants |
| DTG 50 mg Once a Day | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 338 Participants |
| RTG 400 mg BID | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 356 Participants |
| RTG 400 mg BID | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 321 Participants |
Secondary
Number of Participants With Plasma HIV-1 RNA <50 c/mL
The number of participants with plasma HIV-1 RNA level \<50 c/mL was assessed at Week 96.
Time frame: Week 96
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg Once a Day | Number of Participants With Plasma HIV-1 RNA <50 c/mL | 332 Participants |
| RTG 400 mg BID | Number of Participants With Plasma HIV-1 RNA <50 c/mL | 314 Participants |
Secondary
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)
All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Safety Population: all participants who received at least one dose of investigational product
Time frame: From Baseline until Week 96
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypokalemia | 10 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Creatinine | 11 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyponatremia | 34 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | AST | 67 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | LDL cholesterol calculation | 74 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyperglycaemia | 70 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Lipase | 55 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Cholesterol | 90 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Phosphorus, inorganic | 65 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyperkalemia | 7 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Total bilirubin | 27 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | ALP | 7 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Triglycerides | 7 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypernatremia | 4 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hemoglobin | 10 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | CK | 61 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Platelet count | 19 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypoglycaemia | 17 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Total neutrophils | 54 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | CO2 content/bicarbonate | 58 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | White Blood Cell count | 19 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | ALT | 57 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | White Blood Cell count | 7 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | ALT | 70 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | ALP | 15 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | AST | 75 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | CO2 content/bicarbonate | 67 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Cholesterol | 73 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | CK | 47 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Creatinine | 7 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyperglycaemia | 87 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyperkalemia | 4 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypernatremia | 6 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypoglycaemia | 27 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hypokalemia | 15 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hyponatremia | 48 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | LDL cholesterol calculation | 49 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Lipase | 62 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Phosphorus, inorganic | 71 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Total bilirubin | 24 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Triglycerides | 8 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Hemoglobin | 5 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Platelet count | 19 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) | Total neutrophils | 48 Participants |
Secondary
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences
Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline to a CDC CAT C event (EV); CDC CAT B at Baseline to a CDC CAT C EV; CDC CAT C at Baseline to a new CDC CAT C EV; or CDC CAT A, B, or C at Baseline to death.
Time frame: From Baseline until Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any category condition | 10 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any Category B condition | 3 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any Category C condition | 6 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any death | 1 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT A to CAT C | 4 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT B to CAT C | 3 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT C to new CAT C | 0 Participants |
| DTG 50 mg Once a Day | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT A, B, or C to death | 1 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT A, B, or C to death | 1 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any category condition | 8 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT A to CAT C | 2 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any Category B condition | 3 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT C to new CAT C | 1 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any Category C condition | 4 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Progression from CAT B to CAT C | 1 Participants |
| RTG 400 mg BID | Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences | Any death | 1 Participants |