Infection, Human Immunodeficiency Virus
Conditions
Keywords
GSK1349572, emtricitabine, tenofovir, efavirenz, abacavir, antiretroviral therapy naive, dose selection, HIV-1 Infection, integrase inhibitor, HIV infection, once daily, lamivudine
Brief summary
This Phase IIb study in HIV-infected antiretroviral naive subjects will select an optimal once daily dose of GSK1349572 from a range of doses for future evaluation.
Detailed description
This Phase IIb study in HIV-infected antiretroviral naive adult subjects will include a dose-ranging evaluation of GSK1349572 10mg, 25mg and 50mg once daily blinded doses and a control arm of open label efavirenz 600mg once daily. Background ART for all study subjects will be chosen by the investigators and will be either Truvada or Epzicom/Kivexa. Data from the three doses of GSK1349572 will be compared on the basis of antiviral activity, safety/tolerability and pharmacokinetics over 16-24 weeks. Several planned interim analyses will evaluate data in real time; any doses considered inferior will be dropped and subjects on those doses of GSK1349572 will have the option to switch to either the highest dose still under investigation or the selected dose. Subjects will be able to remain in the study, unless they reach a stopping criterion, for at least 96 weeks. 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
DRUGGSK1349572
investigational HIV-1 integrase inhibitor
DRUGefavirenz
approved therapy for HIV-1 infection, used as an internal study control
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
* HIV-1 infected male or female adults at least 18 years of age. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol); * HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL; * CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines dictate); * ART-naive (less than or equal to 10 days of prior therapy with any antiretroviral agent). Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will be exclusionary. * No evidence of viral resistance to any antiretroviral drug indicative of primary transmitted resistance at screening; * Able to understand and comply with protocol requirements; * Able to provide written informed consent prior to screening; * 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. Note: Subjects starting abacavir as part of the NRTI backbone must have been screened and be negative for the HLA-B\*5701 allele.
Exclusion criteria
* Any pre-existing or serious mental or physical disorder which could compromise ability to comply with the protocol or compromise subject safety; * Women who are pregnant or breastfeeding; * An active AIDS-defining condition at the screening visit; * Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives; * History of clinically relevant pancreatitis or hepatitis within the previous 6 months, including HBsAg positive result. Asymptomatic HCV infection will not be exclusionary, however subject who will require HCV therapy during the trial should be excluded. Any subject with a history of liver cirrhosis with or without hepatitis viral co-infection will be excluded. * Any condition which could interfere with the absorption, distribution, metabolism or excretion of the drug; * Any acute or Grade 4 laboratory abnormality at screening; * History of upper gastrointestinal bleed and/or subjects with active peptic ulcer disease; * Estimated creatinine clearance \<50 mL/min; * Alanine aminotransferase (ALT) greater than or equal to 5 times ULN; * Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with \>35% direct bilirubin); * Lipase greater than or equal to 3xULN; * Hemoglobin \< 100 g/L(10 g/dL); * History of allergy to the study drugs or their components or drugs of their class; * Treatment with radiation therapy, cytotoxic chemotherapeutic agents, any agents with activity against HIV-1 or immunomodulators within 28 days prior to screening; * Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening; * History of protocol-defined cardiac diseases; * Personal or family history of prolonged QT syndrome; * Any clinically significant finding, as specified in the protocol, on electrocardiograph (ECG); * Significant blood loss in excess of 500 mL within a 56 day period prior to screening visit; * Immunization within 30 days prior to first dose of investigational product; * French subjects: The subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 | Week 16 | Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Change Over the Initial 2 Weeks of Treatment | Baseline and Week 2 | Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline. Only those participants available at the specified time point were analyzed. |
| Change From Baseline in HIV-1 RNA at the Indicated Time Points | Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 | Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. |
| Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 | Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population. |
| Number of Participants With New HIV-associated Conditions of the Indicated Class | From Baseline up to Week 96 | HIV-associated conditions were 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 acquired immunodeficiency syndrome (AIDS) surveillance case definition. |
| Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | From Baseline up to 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: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death. |
| Number of Participants With Plasma HIV-1 RNA <50 c/mL | Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 | Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. |
| Number of Participants With Plasma HIV-1 RNA <400 c/mL | Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 | Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. |
| Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | From Baseline up to Week 96/Early Withdrawal | An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (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. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold \>=3%) and SAEs. |
| Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | From Baseline up to Week 96/Early Withdrawal | Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening). |
| Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | From Baseline up to Week 96/Early Withdrawal | For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL.On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures. |
| Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | From Baseline up to Week 96/Early Withdrawal | The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL.On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data |
| Plasma DTG Concentration | Week 2, Week 12, and Week 24 | Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population. |
| AUC(0-tau) of DTG | Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 | The area under the time concentration curve over the dosing interval (AUC\[0-tau\]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed. |
| Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 | The Cmax, Cmax, and Ctau of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. |
| Pre-dose Concentration (C0) and C0 Avg of DTG | Week 2, Week 12, and Week 24 | The plasma DTG C0 of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population. |
| Time to Maximal Drug Concentration (Tmax) of DTG | Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 | Tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. |
| Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Week 2 | Relationships between Week 2 plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], and Ctau \[concentration at the end of the dosing interval\]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures |
| Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Week 96 | Relationships between plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], C0avg \[average pre-dose concentration\], and Ctau \[concentration at the end of the dosing interval\]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles) |
| Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Week 96 | Relationships between log-transformed plasma DTG PK parameters (AUC\[0-tau\], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase \[ALT\], change from Baseline \[CFB\] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol \[TC\], CFB in TC) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of \>=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline. |
| Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Week 96 | Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], Ctau \[concentration at the end of the dosing interval\], and C0avg \[average pre-dose concentration\]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).Only those participants available at the specified time points were analyzed represented by n=X in the category titles |
| Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | From Baseline up to Week 96/Early Withdrawal | For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points | Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 | Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized. |
Countries
France, Germany, Italy, Russia, Spain, United States
Participant flow
Recruitment details
Randomization Phase participants received Dolutegravir (DTG 10, 25 or 50 milligrams\[mg\]) with Placebo/Efavirenz (EFV) for 96 Weeks . DTG participants who completed 96 Weeks continued or were switched to receive DTG 50 mg in Open label phase until DTG was locally available.
Pre-assignment details
A total of 278 par were screened of which 70 were screen failures and 208 were randomized; 205 received at least one dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population. 17 participants out of 155 from DTG arm withdrew during Randomization phase and total 138 participants were enrolled in an Open-label phase.
Participants by arm
| Arm | Count |
|---|---|
| DTG 10 mg QD Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. | 53 |
| DTG 25 mg QD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. | 51 |
| DTG 50 mg QD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. | 51 |
| EFV 600 mg QD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. | 50 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Open-label Phase | Adverse Event | 0 | 0 | 0 | 0 | 3 |
| Open-label Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 |
| Open-label Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 12 |
| Open-label Phase | Physician Decision | 0 | 0 | 0 | 0 | 8 |
| Open-label Phase | Protocol Violation | 0 | 0 | 0 | 0 | 12 |
| Open-label Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 14 |
| Randomization Phase 96 Week | Adverse Event | 1 | 1 | 2 | 5 | 0 |
| Randomization Phase 96 Week | Lack of Efficacy | 1 | 1 | 0 | 0 | 0 |
| Randomization Phase 96 Week | Lost to Follow-up | 0 | 3 | 1 | 2 | 0 |
| Randomization Phase 96 Week | Protocol-Defined Stopping Criteria | 0 | 0 | 0 | 1 | 0 |
| Randomization Phase 96 Week | Protocol Violation | 1 | 1 | 1 | 0 | 0 |
| Randomization Phase 96 Week | Withdrawal by Subject | 2 | 1 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | DTG 25 mg QD | DTG 50 mg QD | DTG 10 mg QD | EFV 600 mg QD | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.0 Years STANDARD_DEVIATION 9.79 | 37.0 Years STANDARD_DEVIATION 8.89 | 34.2 Years STANDARD_DEVIATION 9.25 | 40.7 Years STANDARD_DEVIATION 11.19 | 37.2 Years STANDARD_DEVIATION 10 |
| Race/Ethnicity, Customized African American/African Heritage (HER) | 6 participants | 8 participants | 7 participants | 4 participants | 25 participants |
| Race/Ethnicity, Customized African American/African HER & White | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 4 participants | 1 participants | 2 participants | 10 participants |
| Race/Ethnicity, Customized Asian & White | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Japanese/East Asian HER/South East Asian HER | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 0 participants | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized White | 42 participants | 38 participants | 41 participants | 43 participants | 164 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants | 6 Participants | 28 Participants |
| Sex: Female, Male Male | 46 Participants | 45 Participants | 42 Participants | 44 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 53 | 0 / 51 | 0 / 51 | 0 / 50 | 2 / 138 |
| other Total, other adverse events | 49 / 53 | 46 / 51 | 45 / 51 | 46 / 50 | 112 / 138 |
| serious Total, serious adverse events | 6 / 53 | 4 / 51 | 7 / 51 | 7 / 50 | 16 / 138 |
Outcome results
Primary
Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16
Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication
Time frame: Week 16
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 10 mg QD | Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 | 51 participants |
| DTG 25 mg QD | Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 | 47 participants |
| DTG 50 mg QD | Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 | 46 participants |
| EFV 600 mg QD | Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 | 29 participants |
Secondary
AUC(0-tau) of DTG
The area under the time concentration curve over the dosing interval (AUC\[0-tau\]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed.
Time frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
Population: PK Summary Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DTG 10 mg QD | AUC(0-tau) of DTG | 16.0 Hours*µg/mL | Geometric Coefficient of Variation 40 |
| DTG 25 mg QD | AUC(0-tau) of DTG | 23.1 Hours*µg/mL | Geometric Coefficient of Variation 48 |
| DTG 50 mg QD | AUC(0-tau) of DTG | 48.1 Hours*µg/mL | Geometric Coefficient of Variation 40 |
Secondary
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points
Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Population: ITT-E Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | 85.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 60, n=51, 48, 47, 43 | 265.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 32, n=50, 48, 47, 44 | 221.5 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | 75.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 40, n=50, 48, 47, 44 | 205.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 48, n=51, 47, 47, 45 | 204.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 8, n=52, 50, 49, 44 | 118.5 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 2, n=53, 50, 50, 47 | 75.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 84, n=51, 47, 46, 42 | 292.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 12, n=53, 48, 48, 45 | 139.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 16, n=52, 49, 49, 44 | 153.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | 236.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | 163.5 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | 335.0 Cells per cubic millimeter |
| DTG 10 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 24, n=51, 49, 47, 44 | 159.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 24, n=51, 49, 47, 44 | 206.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 60, n=51, 48, 47, 43 | 278.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 12, n=53, 48, 48, 45 | 137.5 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 32, n=50, 48, 47, 44 | 195.5 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 2, n=53, 50, 50, 47 | 79.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 48, n=51, 47, 47, 45 | 249.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | 285.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 40, n=50, 48, 47, 44 | 204.5 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | 89.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | 200.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | 391.5 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 84, n=51, 47, 46, 42 | 313.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 16, n=52, 49, 49, 44 | 176.0 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 8, n=52, 50, 49, 44 | 156.5 Cells per cubic millimeter |
| DTG 25 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | 94.5 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 24, n=51, 49, 47, 44 | 167.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | 75.5 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 2, n=53, 50, 50, 47 | 99.5 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | 110.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 8, n=52, 50, 49, 44 | 129.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 12, n=53, 48, 48, 45 | 171.5 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 16, n=52, 49, 49, 44 | 160.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | 139.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 32, n=50, 48, 47, 44 | 203.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 40, n=50, 48, 47, 44 | 224.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 48, n=51, 47, 47, 45 | 223.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 60, n=51, 48, 47, 43 | 229.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | 220.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 84, n=51, 47, 46, 42 | 280.0 Cells per cubic millimeter |
| DTG 50 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | 326.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | 136.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 2, n=53, 50, 50, 47 | 55.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 60, n=51, 48, 47, 43 | 221.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 16, n=52, 49, 49, 44 | 115.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 12, n=53, 48, 48, 45 | 127.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | 42.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | 195.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 8, n=52, 50, 49, 44 | 104.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | 89.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | 301.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 40, n=50, 48, 47, 44 | 171.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 32, n=50, 48, 47, 44 | 146.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 84, n=51, 47, 46, 42 | 296.5 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 48, n=51, 47, 47, 45 | 174.0 Cells per cubic millimeter |
| EFV 600 mg QD | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points | Week 24, n=51, 49, 47, 44 | 109.5 Cells per cubic millimeter |
Secondary
Change From Baseline in HIV-1 RNA at the Indicated Time Points
Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | -1.815 Log10 c/mL | Standard Deviation 0.3999 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 60, n=50, 48, 48, 44 | -2.741 Log10 c/mL | Standard Deviation 0.6444 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 32, n=52, 49, 47, 45 | -2.717 Log10 c/mL | Standard Deviation 0.6588 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | -2.629 Log10 c/mL | Standard Deviation 0.5863 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 40, n=51, 48, 47, 44 | -2.647 Log10 c/mL | Standard Deviation 0.7039 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 48, n=51, 48, 48, 45 | -2.723 Log10 c/mL | Standard Deviation 0.6519 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 8, n=52, 50, 49, 45 | -2.657 Log10 c/mL | Standard Deviation 0.698 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 2, n=53, 50, 50, 48 | -2.387 Log10 c/mL | Standard Deviation 0.4595 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 84, n=51, 47, 47, 43 | -2.725 Log10 c/mL | Standard Deviation 0.6506 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 12, n=53, 49, 49, 45 | -2.685 Log10 c/mL | Standard Deviation 0.6831 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 16, n=52, 49, 49, 45 | -2.718 Log10 c/mL | Standard Deviation 0.6593 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | -2.742 Log10 c/mL | Standard Deviation 0.6453 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | -2.701 Log10 c/mL | Standard Deviation 0.6423 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | -2.728 Log10 c/mL | Standard Deviation 0.6494 |
| DTG 10 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 24, n=52, 49, 48, 45 | -2.700 Log10 c/mL | Standard Deviation 0.6261 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 24, n=52, 49, 48, 45 | -2.657 Log10 c/mL | Standard Deviation 0.6969 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 60, n=50, 48, 48, 44 | -2.675 Log10 c/mL | Standard Deviation 0.7012 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 12, n=53, 49, 49, 45 | -2.671 Log10 c/mL | Standard Deviation 0.685 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 32, n=52, 49, 47, 45 | -2.658 Log10 c/mL | Standard Deviation 0.6991 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 2, n=53, 50, 50, 48 | -2.365 Log10 c/mL | Standard Deviation 0.5458 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 48, n=51, 48, 48, 45 | -2.667 Log10 c/mL | Standard Deviation 0.6934 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | -2.622 Log10 c/mL | Standard Deviation 0.8052 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 40, n=51, 48, 47, 44 | -2.665 Log10 c/mL | Standard Deviation 0.7051 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | -2.583 Log10 c/mL | Standard Deviation 0.6337 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | -2.662 Log10 c/mL | Standard Deviation 0.6908 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | -2.680 Log10 c/mL | Standard Deviation 0.7116 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 84, n=51, 47, 47, 43 | -2.670 Log10 c/mL | Standard Deviation 0.7064 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 16, n=52, 49, 49, 45 | -2.668 Log10 c/mL | Standard Deviation 0.6826 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 8, n=52, 50, 49, 45 | -2.666 Log10 c/mL | Standard Deviation 0.6667 |
| DTG 25 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | -1.773 Log10 c/mL | Standard Deviation 0.465 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 24, n=52, 49, 48, 45 | -2.853 Log10 c/mL | Standard Deviation 0.6889 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | -1.738 Log10 c/mL | Standard Deviation 0.384 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 2, n=53, 50, 50, 48 | -2.392 Log10 c/mL | Standard Deviation 0.4241 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | -2.713 Log10 c/mL | Standard Deviation 0.5471 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 8, n=52, 50, 49, 45 | -2.848 Log10 c/mL | Standard Deviation 0.6556 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 12, n=53, 49, 49, 45 | -2.860 Log10 c/mL | Standard Deviation 0.6772 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 16, n=52, 49, 49, 45 | -2.859 Log10 c/mL | Standard Deviation 0.6876 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | -2.869 Log10 c/mL | Standard Deviation 0.6896 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 32, n=52, 49, 47, 45 | -2.855 Log10 c/mL | Standard Deviation 0.6963 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 40, n=51, 48, 47, 44 | -2.855 Log10 c/mL | Standard Deviation 0.6934 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 48, n=51, 48, 48, 45 | -2.850 Log10 c/mL | Standard Deviation 0.6849 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 60, n=50, 48, 48, 44 | -2.825 Log10 c/mL | Standard Deviation 0.7458 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | -2.860 Log10 c/mL | Standard Deviation 0.693 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 84, n=51, 47, 47, 43 | -2.855 Log10 c/mL | Standard Deviation 0.6923 |
| DTG 50 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | -2.854 Log10 c/mL | Standard Deviation 0.7061 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 20, n=52, 48, 49, 44 | -2.745 Log10 c/mL | Standard Deviation 0.6602 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 2, n=53, 50, 50, 48 | -1.930 Log10 c/mL | Standard Deviation 0.4312 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 60, n=50, 48, 48, 44 | -2.765 Log10 c/mL | Standard Deviation 0.7035 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 16, n=52, 49, 49, 45 | -2.698 Log10 c/mL | Standard Deviation 0.6715 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 12, n=53, 49, 49, 45 | -2.603 Log10 c/mL | Standard Deviation 0.5869 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 1, n=53, 50, 48, 50 | -1.562 Log10 c/mL | Standard Deviation 0.4158 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 72, n=51, 47, 48, 44 | -2.757 Log10 c/mL | Standard Deviation 0.7094 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 8, n=52, 50, 49, 45 | -2.450 Log10 c/mL | Standard Deviation 0.5989 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 4, n=53, 50, 50, 45 | -2.162 Log10 c/mL | Standard Deviation 0.54 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 96, n=48, 44, 46, 39 | -2.807 Log10 c/mL | Standard Deviation 0.7238 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 40, n=51, 48, 47, 44 | -2.795 Log10 c/mL | Standard Deviation 0.7169 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 32, n=52, 49, 47, 45 | -2.772 Log10 c/mL | Standard Deviation 0.7021 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 84, n=51, 47, 47, 43 | -2.743 Log10 c/mL | Standard Deviation 0.7321 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 48, n=51, 48, 48, 45 | -2.711 Log10 c/mL | Standard Deviation 0.7765 |
| EFV 600 mg QD | Change From Baseline in HIV-1 RNA at the Indicated Time Points | Week 24, n=52, 49, 48, 45 | -2.773 Log10 c/mL | Standard Deviation 0.7026 |
Secondary
Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG
The Cmax, Cmax, and Ctau of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
Population: PK Summary Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 10 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmin | 0.33 µg/mL | Geometric Coefficient of Variation 64 |
| DTG 10 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmax | 1.10 µg/mL | Geometric Coefficient of Variation 37 |
| DTG 10 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Ctau | 0.37 µg/mL | Geometric Coefficient of Variation 55 |
| DTG 25 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmin | 0.44 µg/mL | Geometric Coefficient of Variation 68 |
| DTG 25 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmax | 1.71 µg/mL | Geometric Coefficient of Variation 43 |
| DTG 25 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Ctau | 0.45 µg/mL | Geometric Coefficient of Variation 71 |
| DTG 50 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmax | 3.40 µg/mL | Geometric Coefficient of Variation 27 |
| DTG 50 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Ctau | 1.05 µg/mL | Geometric Coefficient of Variation 72 |
| DTG 50 mg QD | Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG | Cmin | 0.94 µg/mL | Geometric Coefficient of Variation 74 |
Secondary
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (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. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold \>=3%) and SAEs.
Time frame: From Baseline up to Week 96/Early Withdrawal
Population: Safety Population:All participants who received at least one dose of the study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any AE | 50 Participants |
| DTG 10 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any SAE | 5 Participants |
| DTG 25 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any SAE | 5 Participants |
| DTG 25 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any AE | 46 Participants |
| DTG 50 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any AE | 46 Participants |
| DTG 50 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any SAE | 7 Participants |
| EFV 600 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any AE | 46 Participants |
| EFV 600 mg QD | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) | Any SAE | 7 Participants |
Secondary
Number of Participants With New HIV-associated Conditions of the Indicated Class
HIV-associated conditions were 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 acquired immunodeficiency syndrome (AIDS) surveillance case definition.
Time frame: From Baseline up to Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category B | 2 Participants |
| DTG 10 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Death | 1 Participants |
| DTG 10 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category C | 0 Participants |
| DTG 25 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category B | 0 Participants |
| DTG 25 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Death | 0 Participants |
| DTG 25 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category C | 0 Participants |
| DTG 50 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category C | 1 Participants |
| DTG 50 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category B | 1 Participants |
| DTG 50 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Death | 0 Participants |
| EFV 600 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category B | 1 Participants |
| EFV 600 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Death | 0 Participants |
| EFV 600 mg QD | Number of Participants With New HIV-associated Conditions of the Indicated Class | Category C | 0 Participants |
Secondary
Number of Participants With Plasma HIV-1 RNA <400 c/mL
Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Baseline | 0 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 8 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 40 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 20 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 1 | 25 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 12 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 4 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 16 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 84 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 72 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 32 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 2 | 45 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 46 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 24 | 52 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 60 | 50 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 20 | 48 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 60 | 46 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 72 | 46 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 4 | 49 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 84 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 43 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 8 | 49 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 12 | 49 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 1 | 20 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 16 | 48 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Baseline | 0 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 24 | 47 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 32 | 47 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 2 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 40 | 47 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 2 | 41 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 24 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 4 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 84 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 60 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 32 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Baseline | 0 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 12 | 49 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 72 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 16 | 49 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 1 | 16 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 8 | 49 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 40 | 48 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 20 | 49 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 96 | 39 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Baseline | 0 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 1 | 15 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 2 | 23 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 4 | 32 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 8 | 41 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 12 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 16 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 20 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 24 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 32 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 40 | 45 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 48 | 44 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 60 | 44 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 72 | 43 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <400 c/mL | Week 84 | 42 Participants |
Secondary
Number of Participants With Plasma HIV-1 RNA <50 c/mL
Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 8 | 46 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 1 | 6 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 2 | 22 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 4 | 37 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Baseline | 0 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 12 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 16 | 51 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 20 | 51 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 24 | 51 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 32 | 50 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 40 | 49 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 48 | 48 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 60 | 48 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 72 | 48 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 84 | 47 Participants |
| DTG 10 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 96 | 42 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 12 | 46 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 24 | 46 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 96 | 40 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 48 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 84 | 43 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 32 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 2 | 19 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 40 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 8 | 45 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 16 | 46 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 4 | 35 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 1 | 4 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 60 | 44 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 20 | 47 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 72 | 44 Participants |
| DTG 25 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Baseline | 0 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 12 | 45 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 8 | 43 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 72 | 45 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 16 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 20 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 96 | 45 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 24 | 47 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 32 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 84 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 40 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 48 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Baseline | 0 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 1 | 4 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 60 | 46 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 2 | 11 Participants |
| DTG 50 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 4 | 31 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 96 | 36 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 20 | 38 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 2 | 6 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Baseline | 0 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 72 | 40 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 16 | 29 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 60 | 41 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 1 | 3 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 8 | 18 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 32 | 43 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 12 | 25 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 40 | 42 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 84 | 38 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 24 | 41 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 4 | 9 Participants |
| EFV 600 mg QD | Number of Participants With Plasma HIV-1 RNA <50 c/mL | Week 48 | 40 Participants |
Secondary
Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL.On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data
Time frame: From Baseline up to Week 96/Early Withdrawal
Population: On-treatment Phenotypic Resistance Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 1-<2 fold | 2 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 4-<8 fold | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 2-<4 fold | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | >=8 fold | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | <1 fold | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | >=8 fold | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | <1 fold | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 1-<2 fold | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 2-<4 fold | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 4-<8 fold | 0 Participants |
Secondary
Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities
Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).
Time frame: From Baseline up to Week 96/Early Withdrawal
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Phosphate, inorganic | 9 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypoglycaemia | 3 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total neutrophils | 9 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total bilirubin | 3 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypokalemia | 4 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Triglycerides | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyponatremia | 6 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Low-density lipoprotein cholesterol | 14 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Cholesterol | 18 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Magnesium | 7 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alkaline phosphatase | 1 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Prothrombin time | 7 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Amylase | 2 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Aspartate amino transferase | 12 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | White blood cell count | 1 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Platelet count | 1 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Carbon dioxide content/bicarbonate | 28 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine kinase | 17 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | International normalized ratio | 6 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypercalcemia | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alanine amino transferase | 7 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperglycaemia | 16 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hemoglobin | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperkalemia | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Lipase | 11 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypernatremia | 1 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Activated partial thromboplastin time | 7 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypocalcemia | 4 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypercalcemia | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | White blood cell count | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total bilirubin | 4 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Aspartate amino transferase | 8 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypoglycaemia | 3 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperkalemia | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hemoglobin | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypernatremia | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypokalemia | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Carbon dioxide content/bicarbonate | 24 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Phosphate, inorganic | 15 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperglycaemia | 15 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyponatremia | 12 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Triglycerides | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypocalcemia | 5 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | International normalized ratio | 9 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Low-density lipoprotein cholesterol | 15 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total neutrophils | 7 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Magnesium | 6 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine | 4 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Prothrombin time | 8 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine kinase | 6 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alkaline phosphatase | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Cholesterol | 16 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Activated partial thromboplastin time | 12 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Lipase | 13 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Amylase | 3 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alanine amino transferase | 11 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Platelet count | 4 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total neutrophils | 6 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alanine amino transferase | 3 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Cholesterol | 13 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine kinase | 7 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Lipase | 11 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Triglycerides | 2 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alkaline phosphatase | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Amylase | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Aspartate amino transferase | 6 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Carbon dioxide content/bicarbonate | 23 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypercalcemia | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperglycaemia | 17 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperkalemia | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypernatremia | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypocalcemia | 5 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypoglycaemia | 5 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypokalemia | 3 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyponatremia | 7 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Low-density lipoprotein cholesterol | 11 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Magnesium | 5 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Phosphate, inorganic | 14 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total bilirubin | 3 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Activated partial thromboplastin time | 6 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hemoglobin | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | International normalized ratio | 6 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Platelet count | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Prothrombin time | 7 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | White blood cell count | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Lipase | 9 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total bilirubin | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypernatremia | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperkalemia | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine kinase | 5 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Activated partial thromboplastin time | 5 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyperglycaemia | 17 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypercalcemia | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Total neutrophils | 10 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hemoglobin | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Creatinine | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Carbon dioxide content/bicarbonate | 30 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Cholesterol | 24 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | International normalized ratio | 5 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Aspartate amino transferase | 9 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Amylase | 4 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alanine amino transferase | 19 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Platelet count | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Alkaline phosphatase | 10 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Triglycerides | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Low-density lipoprotein cholesterol | 20 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | White blood cell count | 1 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Magnesium | 4 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hyponatremia | 13 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypokalemia | 3 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Prothrombin time | 4 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Phosphate, inorganic | 11 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypoglycaemia | 4 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities | Hypocalcemia | 8 Participants |
Secondary
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL.On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.
Time frame: From Baseline up to Week 96/Early Withdrawal
Population: On-treatment Genotypic Resistance Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | A23A/V | 1 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | S255N | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | A23A/V | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | S255N | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | A23A/V | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | S255N | 0 Participants |
Secondary
Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of \<1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24 without evidence of prior suppression to \<400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL; confirmed plasma HIV-1 RNA levels \>0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value \>=400 copies/mL.
Time frame: From Baseline up to Week 96/Early Withdrawal
Population: On-treatment Genotypic Resistance Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 10 mg QD | Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance | 0 Participants |
Secondary
Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)
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: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death.
Time frame: From Baseline up to Week 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT C at Baseline to a new CAT C event | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A at Baseline to a CAT C event | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT B at Baseline to a CAT C event | 0 Participants |
| DTG 10 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A, B, or C at Baseline to death | 1 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A, B, or C at Baseline to death | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT C at Baseline to a new CAT C event | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A at Baseline to a CAT C event | 0 Participants |
| DTG 25 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT B at Baseline to a CAT C event | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT B at Baseline to a CAT C event | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A at Baseline to a CAT C event | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT C at Baseline to a new CAT C event | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A, B, or C at Baseline to death | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT B at Baseline to a CAT C event | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A at Baseline to a CAT C event | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT A, B, or C at Baseline to death | 0 Participants |
| EFV 600 mg QD | Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) | CAT C at Baseline to a new CAT C event | 0 Participants |
Secondary
Plasma DTG Concentration
Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.
Time frame: Week 2, Week 12, and Week 24
Population: PK Summary Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 10 mg QD | Plasma DTG Concentration | Week 24, 2-4 hours post-dose, n=45, 45, 45, 0 | 1.0113 Micrograms per milliliter (µg/mL) | Standard Deviation 0.34083 |
| DTG 10 mg QD | Plasma DTG Concentration | Week 12, Pre-dose, n= 46, 45, 44, 0 | 0.3648 Micrograms per milliliter (µg/mL) | Standard Deviation 0.16791 |
| DTG 10 mg QD | Plasma DTG Concentration | Week 24, Pre-dose, n=45, 44, 44, 0 | 0.3766 Micrograms per milliliter (µg/mL) | Standard Deviation 0.23399 |
| DTG 10 mg QD | Plasma DTG Concentration | Week 2, Pre-dose, n=46, 44, 43, 0 | 0.3580 Micrograms per milliliter (µg/mL) | Standard Deviation 0.18321 |
| DTG 10 mg QD | Plasma DTG Concentration | Week 12, 2-4 hours post-dose, n=48, 45, 45, 0 | 1.0374 Micrograms per milliliter (µg/mL) | Standard Deviation 0.27517 |
| DTG 10 mg QD | Plasma DTG Concentration | Week 2, 2-4 hours post-dose, n=31, 29, 29, 0 | 1.0121 Micrograms per milliliter (µg/mL) | Standard Deviation 0.28125 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 12, 2-4 hours post-dose, n=48, 45, 45, 0 | 1.7907 Micrograms per milliliter (µg/mL) | Standard Deviation 0.70953 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 24, Pre-dose, n=45, 44, 44, 0 | 0.6636 Micrograms per milliliter (µg/mL) | Standard Deviation 0.50767 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 2, 2-4 hours post-dose, n=31, 29, 29, 0 | 1.9716 Micrograms per milliliter (µg/mL) | Standard Deviation 0.7189 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 24, 2-4 hours post-dose, n=45, 45, 45, 0 | 1.9021 Micrograms per milliliter (µg/mL) | Standard Deviation 0.7943 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 2, Pre-dose, n=46, 44, 43, 0 | 0.6779 Micrograms per milliliter (µg/mL) | Standard Deviation 0.44085 |
| DTG 25 mg QD | Plasma DTG Concentration | Week 12, Pre-dose, n= 46, 45, 44, 0 | 0.5759 Micrograms per milliliter (µg/mL) | Standard Deviation 0.32645 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 12, Pre-dose, n= 46, 45, 44, 0 | 1.4169 Micrograms per milliliter (µg/mL) | Standard Deviation 1.00152 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 2, Pre-dose, n=46, 44, 43, 0 | 1.4044 Micrograms per milliliter (µg/mL) | Standard Deviation 0.88041 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 2, 2-4 hours post-dose, n=31, 29, 29, 0 | 3.8414 Micrograms per milliliter (µg/mL) | Standard Deviation 1.87405 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 24, 2-4 hours post-dose, n=45, 45, 45, 0 | 3.5397 Micrograms per milliliter (µg/mL) | Standard Deviation 1.36538 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 12, 2-4 hours post-dose, n=48, 45, 45, 0 | 3.6056 Micrograms per milliliter (µg/mL) | Standard Deviation 1.33862 |
| DTG 50 mg QD | Plasma DTG Concentration | Week 24, Pre-dose, n=45, 44, 44, 0 | 1.4534 Micrograms per milliliter (µg/mL) | Standard Deviation 0.94283 |
Secondary
Pre-dose Concentration (C0) and C0 Avg of DTG
The plasma DTG C0 of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.
Time frame: Week 2, Week 12, and Week 24
Population: PK Summary Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 10 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 2, n=46, 44, 43, 0 | 0.31 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 58 |
| DTG 10 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 12, n=46, 45, 44, 0 | 0.33 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 49 |
| DTG 10 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 24, n=45, 44, 44, 0 | 0.33 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 67 |
| DTG 10 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0 avg, n=48, 46, 46, 0 | 0.34 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 49 |
| DTG 25 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0 avg, n=48, 46, 46, 0 | 0.56 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 61 |
| DTG 25 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 2, n=46, 44, 43, 0 | 0.57 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 62 |
| DTG 25 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 24, n=45, 44, 44, 0 | 0.57 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 74 |
| DTG 25 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 12, n=46, 45, 44, 0 | 0.47 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 77 |
| DTG 50 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0 avg, n=48, 46, 46, 0 | 1.25 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 55 |
| DTG 50 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 12, n=46, 45, 44, 0 | 1.13 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 95 |
| DTG 50 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 24, n=45, 44, 44, 0 | 1.20 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 74 |
| DTG 50 mg QD | Pre-dose Concentration (C0) and C0 Avg of DTG | C0, Week 2, n=46, 44, 43, 0 | 1.20 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 61 |
Secondary
Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters
Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], Ctau \[concentration at the end of the dosing interval\], and C0avg \[average pre-dose concentration\]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).Only those participants available at the specified time points were analyzed represented by n=X in the category titles
Time frame: Week 96
Population: PK/PD Analysis Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Abdominal pain versus AUC(0-tau), n=45 | -2.49 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Abdominal pain versus Cmax, n=45 | -2.98 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Abdominal pain versus Ctau, n=45 | -1.72 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Abdominal pain versus C0avg, n=140 | -0.41 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Diarrhoea versus AUC(0-tau), n=45 | -0.62 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Diarrhoea versus Cmax, n=45 | -0.98 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Diarrhoea versus Ctau, n=45 | -0.29 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Diarrhoea versus C0avg, n=140 | 0.13 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Nausea versus AUC(0-tau), n=45 | -0.31 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Nausea versus Cmax, n=45 | -0.72 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Nausea versus Ctau, n=45 | 0.03 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Nausea versus C0avg, n=140 | -0.32 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Vomiting versus AUC(0-tau), n=45 | -1.29 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Vomiting versus Cmax, n=45 | -1.61 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Vomiting versus Ctau, n=45 | -1.15 estimated effect |
| DTG 10 mg QD | Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters | Vomiting versus C0avg, n=140 | -0.89 estimated effect |
Secondary
Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters
Relationships between plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], C0avg \[average pre-dose concentration\], and Ctau \[concentration at the end of the dosing interval\]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)
Time frame: Week 96
Population: PK/PD Analysis Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau), n=13, 14, 15, 0 | -0.100 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax, n=13, 14, 15, 0 | -0.047 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg, n=43, 40, 42, 0 | -0.009 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau, n=13, 14, 15, 0 | -0.289 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax, n=13, 14, 15, 0 | 0.332 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg, n=43, 40, 42, 0 | -0.013 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau, n=13, 14, 15, 0 | 0.299 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau), n=13, 14, 15, 0 | 0.379 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg, n=43, 40, 42, 0 | 0.206 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax, n=13, 14, 15, 0 | 0.234 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau, n=13, 14, 15, 0 | -0.074 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau), n=13, 14, 15, 0 | 0.008 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau, n=13, 14, 15, 0 | -0.055 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax, n=13, 14, 15, 0 | 0.037 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau), n=13, 14, 15, 0 | -0.005 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg, n=43, 40, 42, 0 | -0.011 Pearson's correlation coefficient |
Secondary
Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
Relationships between Week 2 plasma DTG PK parameters (AUC\[0-tau\] \[area under the time concentration curve over the dosing interval\], Cmax \[maximal concentration\], and Ctau \[concentration at the end of the dosing interval\]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures
Time frame: Week 2
Population: PK/PD Analysis Population.Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) | 0.426 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Ctau | 0.273 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Cmax | 0.452 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) | -0.018 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Ctau | -0.100 Pearson's correlation coefficient |
| DTG 25 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Cmax | -0.051 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Cmax | -0.150 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) | -0.258 Pearson's correlation coefficient |
| DTG 50 mg QD | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Ctau | -0.263 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) | -0.086 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Ctau | -0.129 Pearson's correlation coefficient |
| Overall DTG | Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters | Cmax | -0.055 Pearson's correlation coefficient |
Secondary
Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
Relationships between log-transformed plasma DTG PK parameters (AUC\[0-tau\], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase \[ALT\], change from Baseline \[CFB\] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol \[TC\], CFB in TC) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of \>=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.
Time frame: Week 96
Population: PK/PD Analysis Population.Only those participants available at the specified time points were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus AE occurrence, n=45 | 0.114 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus maximum AE intensity, n=45 | 0.171 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus ALT, n=45 | -0.196 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in ALT, n=45 | -0.201 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus total bilirubin, n=45 | 0.364 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in total bilirubin, n=45 | 0.147 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus creatine kinase, n=45 | -0.168 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in creatine kinase, n=45 | -0.145 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) vs Triglycerides, n=45 | 0.104 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in triglycerides, n=45 | 0.216 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus lipase, n=45 | -0.066 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in lipase, n=45 | 0.092 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus total cholesterol, n=45 | -0.097 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | AUC(0-tau) versus CFB in total cholesterol, n=45 | -0.153 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus AE occurrence, n=45 | 0.061 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus maximum AE intensity, n=45 | 0.110 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus ALT, n=45 | -0.135 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in ALT, n=45 | -0.135 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus total bilirubin, n=45 | 0.265 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in total bilirubin, n=45 | 0.033 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus creatine kinase, n=45 | -0.188 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in creatine kinase, n=45 | -0.161 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus triglycerides, n=45 | 0.134 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in triglycerides, n=45 | 0.244 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus lipase, n=45 | -0.034 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in lipase, n=45 | 0.115 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus total cholesterol, n=45 | -0.101 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmax versus CFB in total cholesterol, n=45 | -0.192 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus AE occurrence, n=133 | -0.080 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus maximum AE intensity, n=133 | -0.003 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus ALT, n=133 | -0.196 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in ALT, n=133 | -0.237 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus total bilirubin, n=133 | 0.298 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in total bilirubin, n=133 | 0.120 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus creatine kinase, n=133 | -0.094 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in creatine kinase, n=133 | -0.093 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus triglycerides, n=133 | -0.058 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in triglycerides, n=133 | -0.012 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus lipase, n=133 | -0.187 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in lipase, n=133 | -0.137 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus total cholesterol, n=133 | -0.179 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0 versus CFB in total cholesterol, n=133 | -0.125 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus AE occurrence, n=140 | -0.028 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus maximum AE intensity, n=140 | 0.036 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus ALT, n=140 | -0.166 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in ALT, n=140 | -0.177 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus total bilirubin, n=140 | 0.319 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in total bilirubin, n=140 | 0.109 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus creatine kinase, n=140 | -0.114 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in creatine kinase, n=140 | -0.110 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus triglycerides, n=140 | 0.057 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in triglycerides, n=140 | 0.092 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus lipase, n=140 | -0.164 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in lipase, n=140 | -0.120 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus total cholesterol, n=140 | -0.170 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | C0avg versus CFB in total cholesterol, n=140 | -0.083 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus AE occurrence, n=45 | 0.190 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus maximum AE intensity, n=45 | 0.205 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus ALT, n=45 | -0.281 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in ALT, n=45 | -0.285 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus total bilirubin, n=45 | 0.446 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in total bilirubin, n=45 | 0.237 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus creatine kinase, n=45 | -0.143 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in creatine kinase, n=45 | -0.125 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus triglycerides, n=45 | 0.061 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in triglycerides, n=45 | 0.172 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus lipase, n=45 | -0.131 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in lipase, n=45 | 0.056 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus total cholesterol, n=45 | -0.039 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Ctau versus CFB in total cholesterol, n=45 | -0.108 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus AE occurrence, n=45 | 0.156 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus maximum AE intensity, n=45 | 0.193 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus ALT, n=45 | -0.236 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in ALT, n=45 | -0.253 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus total bilirubin, n=45 | 0.430 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in total bilirubin, n=45 | 0.171 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus creatine kinase, n=45 | -0.132 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in creatine kinase, n=45 | -0.124 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus triglycerides, n=45 | -0.042 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in triglycerides, n=45 | 0.057 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus lipase, n=45 | -0.135 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in lipase, n=45 | 0.032 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus total cholesterol, n=45 | -0.194 Pearson's correlation coefficient |
| DTG 10 mg QD | Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters | Cmin versus CFB in total cholesterol, n=45 | -0.208 Pearson's correlation coefficient |
Secondary
Time to Maximal Drug Concentration (Tmax) of DTG
Tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
Population: PK Summary Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DTG 10 mg QD | Time to Maximal Drug Concentration (Tmax) of DTG | 2.0 Hours |
| DTG 25 mg QD | Time to Maximal Drug Concentration (Tmax) of DTG | 2.0 Hours |
| DTG 50 mg QD | Time to Maximal Drug Concentration (Tmax) of DTG | 2.0 Hours |
Secondary
Viral Change Over the Initial 2 Weeks of Treatment
Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline. Only those participants available at the specified time point were analyzed.
Time frame: Baseline and Week 2
Population: ITT-E Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTG 10 mg QD | Viral Change Over the Initial 2 Weeks of Treatment | -2.387 Log10 c/mL | Standard Deviation 0.4595 |
| DTG 25 mg QD | Viral Change Over the Initial 2 Weeks of Treatment | -2.365 Log10 c/mL | Standard Deviation 0.5458 |
| DTG 50 mg QD | Viral Change Over the Initial 2 Weeks of Treatment | -2.392 Log10 c/mL | Standard Deviation 0.4241 |
| EFV 600 mg QD | Viral Change Over the Initial 2 Weeks of Treatment | -1.930 Log10 c/mL | Standard Deviation 0.4312 |
Other Pre-specified
Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points
Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized.
Time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Population: ITT-E Population