A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects

Infection, Human Immunodeficiency Virus Clinical Trial

— ING112276  

Official title:

A Phase IIb Study to Select a Once Daily Dose of GSK1349572 Administered With Either Abacavir/Lamivudine or Tenofovir/Emtricitabine in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951015
• Other study ID #: 112276
• Status: Completed
• Phase: Phase 2
• First received: July 30, 2009
• Last updated: December 14, 2017
• Start date: July 30, 2009
• Est. completion date: December 22, 2016

Study information

• Verified date: April 2017
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: December 22, 2016
• Est. primary completion date: February 26, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Infection
• Infection, Human Immunodeficiency Virus

Intervention

Drug:
• GSK1349572
investigational HIV-1 integrase inhibitor
• efavirenz
approved therapy for HIV-1 infection, used as an internal study control

Locations

Country	Name	City	State
France	GSK Investigational Site	Lyon cedex 04
France	GSK Investigational Site	Montpellier Cedex 5
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 10
France	GSK Investigational Site	Paris Cedex 13
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Italy	GSK Investigational Site	Bergamo	Lombardia
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Santa Fe	New Mexico
United States	GSK Investigational Site	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline, Shionogi

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Russian Federation,  Spain, 

References & Publications (1)

van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B, Rockstroh JK, Almond S, Song I, Brothers C, Min S. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis. 2012 Feb;12(2):111-8. doi: 10.1016/S1473-3099(11)70290-0. Epub 2011 Oct 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	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
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	Week 16
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.	Baseline and Week 2
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.	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
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.	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
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.	From Baseline up to Week 96
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.	From Baseline up to Week 96
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.	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
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.	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
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.	From Baseline up to Week 96/Early Withdrawal
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).	From Baseline up to Week 96/Early Withdrawal
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.	From Baseline up to Week 96/Early Withdrawal
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.	From Baseline up to Week 96/Early Withdrawal
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	From Baseline up to Week 96/Early Withdrawal
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.	Week 2, Week 12, and Week 24
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.	Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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.	Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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.	Week 2, Week 12, and Week 24
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.	Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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	Week 2
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)	Week 96
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.	Week 96
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	Week 96