Infection, Human Immunodeficiency Virus
Conditions
Keywords
ritonavir, HIV, HAART, darunavir, antiretroviral, dolutegravir, GSK1349572
Brief summary
This study will be conducted in approximately 468 HIV-1 infected antiretroviral therapy (ART)-naïve subjects. Subjects will be randomized 1:1 to receive dolutegravir (DTG) 50 mg once daily (approximately 234 subjects) or darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual nucleoside reverse transriptase inhibitor (NRTI) therapy (either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). Subjects will be stratified by screening HIV-1 RNA and background NRTI selection. The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.
Detailed description
ING114915 is a Phase IIIb randomized, open-label, active-controlled, multicentre, parallel group, fully-powered non-inferiority study. The study will be conducted in approximately 468 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 to receive DTG 50 mg once daily (approximately 234 subjects) or DRV/r 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC). The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study. Subjects who fulfil eligibility requirements will be randomized 1:1 to receive DTG 50 mg once daily or DRV/r 800 mg/100 mg once daily. In order to achieve balance across the two treatment groups of the study, randomization will be stratified by: screening plasma HIV-1 RNA \>/ 100,000 copies/mL (c/mL) or \> 100,000 c/mL and background dual NRTI (ABC/3TC or TDF/FTC) The DTG and DRV/r doses will be administered in an open-label fashion throughout the study. Subjects randomized to receive DTG and who successfully complete 96 weeks of treatment will continue to have access to DTG until either it is locally approved and commercially available, the patient no longer derives clinical benefit, the patient meets a protocol-defined reason for discontinuation or until development of DTG is terminated. Subjects randomized to the DRV/r arm will receive DRV/r through their Week 96 visit, after which they will be discontinued from the study and will need to make alternative arrangements to access antiretroviral medication. All subjects will receive background dual-NRTI therapy through their Week 96 visit.
Interventions
DRUGdolutegravir 50 mg OAD
1 x 50 mg tablet OAD
DRUGdarunavir 800mg OAD
2 x 400mg tablets OAD
DRUGritonavir 100mg OAD
1 x 100mg tablet OAD
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infected adults greater than or equal to 18 years of age. Females are eligible to enter and participate in the study if she is (1) non-childbearing potential, (2) child bearing potential with negative pregnancy test at screening and Day 1 and agrees to use protocol-specified methods of birth control while on study. * HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL * Antiretroviral-naïve (less than or equal to 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) * Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening
Exclusion criteria
* Women who are pregnant or breastfeeding * Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease \[CDC, 1993\], except cutaneous Kaposi's sarcoma not requiring systemic therapy * Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification * Anticipated need for Hepatitis C virus (HCV) therapy during the study * History or presence of allergy or intolerance to the study drugs or their components or drugs of their class * History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject * Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening * Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators * Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product * Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product * Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation \[IAS-USA, 2010\] in the Screening result or, if known, any historical resistance test result * Any verified Grade 4 laboratory abnormality. Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound is exclusionary * Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal * ALT greater than 3 times the upper limit of normal and bilirubin greater than or equal to 1.5 times the upper limit of normal (with greater than 35% direct bilirubin) * Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method * Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 | Week 48 | Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48 | Week 48 | The percentage of participants with Plasma HIV-1 RNA \<400 c/mL at Week 48 was assessed MSDF, as codified by the FDA snapshot algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). |
| Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48 | Change from Baseline in plasma HIV-1 RNA (log10 c/mL) was assessed at Weeks 4, 8, 12, 16, 24, 36 and 48 . Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population. |
| Change From Baseline in CD4+ and CD8+ Cell Counts | Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+ | Change from Baseline in CD4+ cell counts was assessed at Weeks 4, 8, 12, 16, 36 and 48. Change from Baseline in CD8+ cell counts was assessed at Weeks 4, 12, 24 and 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits and parameters, so the overall number of participants analyzed reflects everyone in the mITT-E Population. |
| Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48 | Week 48 | The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures). |
| Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48 | From Baseline through Week 48 | Fasting LDL cholesterol change from Baseline was analyzed. Values represented are for adjusted means. Estimates are calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, background dual NRTI therapy, Baseline LDL cholesterol, treatment\*visit interaction and Baseline LDL cholesterol\*visit interaction. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed. |
| Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48 | From Baseline through Week 48 | Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for which an increase in fasting LDL cholesterol to Grade 2 or higher occurred. Only those participants with data available at the specified time points were analyzed. |
| Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | From Baseline through Week 48 | Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. |
| Time to Virologic Suppression (<50 Copies/mL) Through Week 48 | From Baseline through Week 48 | The time to viral suppression (i.e. first viral load value \<50 copies/mL) through Week 48 was derived and summarized using Kaplan-Meier plots. Participants who withdrew for any reason without having suppressed prior to the analysis were censored. Confidence intervals were estimated using the Brookmeyer-Crowley method. |
| Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Baseline, Week 4, Week 24, and Week 48 | SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health). Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and baseline symptom bother score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicates a decline in a participant's quality of life over that period. |
| Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 | Baseline, Week 24, and Week 48 | The EQ-5D is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and Baseline EQ-5D utility score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 | Baseline, Week 24, and Week 48 | The European Quality of Life -5 Dimensions (EQ-5D) is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. Thermometer score is based on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, Baseline viral load, background dual NRTI therapy and Baseline EQ-5D thermometer score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 4, Week 24, and Week 48 | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The treatment satisfaction score (range: 0-60) was the sum of the individual items. HIVTSQ mITT-E Population=Only participants from USA, France, Germany, Italy, Spain for whom valid translations were available from the mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 4, Week 24, and Week 48 | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The lifestyle/ease score is the sum of items 4, 5, 6, 7 and 8 (range: 0-30). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 4, Week 24, and Week 48 | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The convenience score is the score for item 5 (range: 0-6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF) | Baseline until PDVF up to Week 48 | An assessment was made of every change across all amino acids within the integrase (IN), reverse transcriptase (RT), and Protease (PRO) encoding region at Baseline and at time of suspected PDVF. PDVF is defined as the confirmed plasma HIV-1 RNA \>200 c/mL \>=Week 24. PDVF Genotypic Population included all participants in the mITT-E population with available on-treatment genotypic resistance data, at time of PDVF. Only those participants with data available at the specified time points were analyzed. |
Countries
France, Germany, Italy, Puerto Rico, Romania, Russia, Spain, Switzerland, United States
Participant flow
Recruitment details
This was a 2 sequential treatment period study. In first period (Randomization phase) participants received either dolutegravir (DTG) 50 milligram (mg) or darunavir (DRV) 800 mg with ritonavir (RTV) 100 mg once daily (QD) for 96 weeks. DTG participants who completed 96 Weeks of DTG then continued to receive DTG 50 mg in Extension phase.
Pre-assignment details
A total of 595 participants were screened; 107 were screen failures; 488 were randomized; 485 received at least 1 dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population of which 1 participant was removed, creating the modified ITT-E population with 484 participants. 123 participants enrolled in Extension Phase.
Participants by arm
| Arm | Count |
|---|---|
| DTG 50 mg QD Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | 242 |
| DRV 800 mg + RTV 100 mg QD Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. | 242 |
| Total | 484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Phase Approximately 3 Years | Adverse Event | 0 | 0 | 2 |
| Extension Phase Approximately 3 Years | Lack of Efficacy | 0 | 0 | 2 |
| Extension Phase Approximately 3 Years | Lost to Follow-up | 0 | 0 | 4 |
| Randomization Phase 96 Week | Adverse Event | 5 | 13 | 0 |
| Randomization Phase 96 Week | Lack of Efficacy | 3 | 4 | 0 |
| Randomization Phase 96 Week | Lost to Follow-up | 15 | 18 | 0 |
| Randomization Phase 96 Week | Other: study closed/terminated | 0 | 1 | 0 |
| Randomization Phase 96 Week | Physician Decision | 2 | 3 | 0 |
| Randomization Phase 96 Week | Protocol-defined Stopping Criteria | 1 | 0 | 0 |
| Randomization Phase 96 Week | Protocol Violation | 5 | 6 | 0 |
| Randomization Phase 96 Week | Withdrawal by Subject | 2 | 8 | 0 |
Baseline characteristics
| Characteristic | DRV 800 mg + RTV 100 mg QD | Total | DTG 50 mg QD |
|---|---|---|---|
| Age, Continuous | 36.2 Years STANDARD_DEVIATION 10.64 | 35.9 Years STANDARD_DEVIATION 10.64 | 35.7 Years STANDARD_DEVIATION 10.66 |
| Race/Ethnicity, Customized African American/African Heritage | 53 Participants | 113 Participants | 60 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 9 Participants | 12 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed Race | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 173 Participants | 342 Participants | 169 Participants |
| Sex: Female, Male Female | 41 Participants | 72 Participants | 31 Participants |
| Sex: Female, Male Male | 201 Participants | 412 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 242 | 0 / 242 | 0 / 123 |
| other Total, other adverse events | 221 / 242 | 214 / 242 | 52 / 123 |
| serious Total, serious adverse events | 36 / 242 | 21 / 242 | 4 / 123 |
Outcome results
Primary
Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48
Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product
Time frame: Week 48
Population: mITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg QD | Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 | 90 Percentage of participants |
| DRV 800 mg + RTV 100 mg QD | Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 | 83 Percentage of participants |
p-value: 0.02595% CI: [0.9, 13.2]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48
SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health). Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and baseline symptom bother score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicates a decline in a participant's quality of life over that period.
Time frame: Baseline, Week 4, Week 24, and Week 48
Population: mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 4, n=218, 210 | -3.20 Scores on a scale | Standard Error 0.56 |
| DTG 50 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 24, n=222, 214 | -2.71 Scores on a scale | Standard Error 0.64 |
| DTG 50 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 48, n= 222, 215 | -2.46 Scores on a scale | Standard Error 0.68 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 4, n=218, 210 | -2.19 Scores on a scale | Standard Error 0.56 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 24, n=222, 214 | -1.65 Scores on a scale | Standard Error 0.65 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 | Week 48, n= 222, 215 | -0.77 Scores on a scale | Standard Error 0.69 |
Secondary
Change From Baseline in CD4+ and CD8+ Cell Counts
Change from Baseline in CD4+ cell counts was assessed at Weeks 4, 8, 12, 16, 36 and 48. Change from Baseline in CD8+ cell counts was assessed at Weeks 4, 12, 24 and 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits and parameters, so the overall number of participants analyzed reflects everyone in the mITT-E Population.
Time frame: Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+
Population: mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 16, n=227, 227 | 156.8 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 146.6 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 48, n=227, 212 | 243.8 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 180.68 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 12, n=234, 228 | 135.2 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 120.03 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 4, n=235, 235 | -47.4 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 276.01 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 24, n=233, 227 | 165.1 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 145.85 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 12, n=231, 227 | -42.0 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 343.81 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 8, n=236, 236 | 126.9 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 124.13 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 24, n=231, 224 | -108.0 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 350.03 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 36, n=232, 218 | 206.1 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 159.06 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 48, n=224, 210 | -109.5 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 360.94 |
| DTG 50 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 4, n=237, 236 | 80.1 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 101.36 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 48, n=224, 210 | -162.1 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 421.07 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 4, n=237, 236 | 75.6 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 124.36 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 8, n=236, 236 | 118.8 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 142.54 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 12, n=234, 228 | 131.8 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 143.88 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 16, n=227, 227 | 146.1 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 166.08 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 24, n=233, 227 | 164.3 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 180 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 36, n=232, 218 | 186.5 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 183.61 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD4+ cell count, Week 48, n=227, 212 | 215.4 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 177.26 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 4, n=235, 235 | -3.7 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 375.94 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 12, n=231, 227 | -68.9 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 373.38 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in CD4+ and CD8+ Cell Counts | CD8+ cell count, Week 24, n=231, 224 | -132.9 Cells per millimeters cubed (cells/mm^3) | Standard Deviation 389.7 |
Secondary
Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48
The European Quality of Life -5 Dimensions (EQ-5D) is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. Thermometer score is based on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, Baseline viral load, background dual NRTI therapy and Baseline EQ-5D thermometer score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24, and Week 48
Population: mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 | Week 24, n=221, 216 | 4.95 Scores on a scale | Standard Error 0.885 |
| DTG 50 mg QD | Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 | Week 48, n=224, 220 | 5.78 Scores on a scale | Standard Error 0.762 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 | Week 24, n=221, 216 | 5.96 Scores on a scale | Standard Error 0.895 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 | Week 48, n=224, 220 | 6.95 Scores on a scale | Standard Error 0.769 |
Secondary
Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48
The EQ-5D is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and Baseline EQ-5D utility score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24, and Week 48
Population: mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 | Week 24, n=217, 213 | 0.00 Scores on a scale | Standard Error 0.012 |
| DTG 50 mg QD | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 | Week 48, n=224, 217 | 0.01 Scores on a scale | Standard Error 0.012 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 | Week 24, n=217, 213 | 0.02 Scores on a scale | Standard Error 0.012 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 | Week 48, n=224, 217 | 0.01 Scores on a scale | Standard Error 0.012 |
Secondary
Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48
Fasting LDL cholesterol change from Baseline was analyzed. Values represented are for adjusted means. Estimates are calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, background dual NRTI therapy, Baseline LDL cholesterol, treatment\*visit interaction and Baseline LDL cholesterol\*visit interaction. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed.
Time frame: From Baseline through Week 48
Population: mSafety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48 | 0.07 Millimoles per liter (mmol/L) | Standard Error 0.041 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48 | 0.37 Millimoles per liter (mmol/L) | Standard Error 0.041 |
Secondary
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in plasma HIV-1 RNA (log10 c/mL) was assessed at Weeks 4, 8, 12, 16, 24, 36 and 48 . Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population.
Time frame: Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48
Population: mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 12, n=234, 227 | -2.88 Log10 copies per mL | Standard Deviation 0.653 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 24, n=234, 227 | -2.86 Log10 copies per mL | Standard Deviation 0.765 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 8, n=237, 236 | -2.86 Log10 copies per mL | Standard Deviation 0.649 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 36, n=232, 218 | -2.87 Log10 copies per mL | Standard Deviation 0.715 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 16, n=229, 228 | -2.86 Log10 copies per mL | Standard Deviation 0.691 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 48, n=227, 212 | -2.89 Log10 copies per mL | Standard Deviation 0.739 |
| DTG 50 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 4, n=238, 235 | -2.80 Log10 copies per mL | Standard Deviation 0.625 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 48, n=227, 212 | -2.86 Log10 copies per mL | Standard Deviation 0.663 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 4, n=238, 235 | -2.01 Log10 copies per mL | Standard Deviation 0.454 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 8, n=237, 236 | -2.40 Log10 copies per mL | Standard Deviation 0.524 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 12, n=234, 227 | -2.61 Log10 copies per mL | Standard Deviation 0.537 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 16, n=229, 228 | -2.71 Log10 copies per mL | Standard Deviation 0.618 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 24, n=234, 227 | -2.83 Log10 copies per mL | Standard Deviation 0.663 |
| DRV 800 mg + RTV 100 mg QD | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 | Week 36, n=232, 218 | -2.85 Log10 copies per mL | Standard Deviation 0.683 |
Secondary
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The convenience score is the score for item 5 (range: 0-6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
Time frame: Week 4, Week 24, and Week 48
Population: HIVTSQ mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 4, n=204, 190 | 5.6 Scores on a scale | Standard Deviation 0.71 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 24, n=211, 200, | 5.6 Scores on a scale | Standard Deviation 0.64 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 48, n=212, 201 | 5.7 Scores on a scale | Standard Deviation 0.62 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 4, n=204, 190 | 5.2 Scores on a scale | Standard Deviation 1.11 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 24, n=211, 200, | 5.4 Scores on a scale | Standard Deviation 1.01 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 | Week 48, n=212, 201 | 5.4 Scores on a scale | Standard Deviation 1.02 |
Secondary
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The lifestyle/ease score is the sum of items 4, 5, 6, 7 and 8 (range: 0-30). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
Time frame: Week 4, Week 24, and Week 48
Population: HIVTSQ mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 4, n=202, 190 | 26.7 Scores on a scale | Standard Deviation 3.61 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 24, n=210, 199 | 27.5 Scores on a scale | Standard Deviation 3.16 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 48, n=211, 201 | 27.6 Scores on a scale | Standard Deviation 3 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 4, n=202, 190 | 25.8 Scores on a scale | Standard Deviation 4.48 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 24, n=210, 199 | 26.6 Scores on a scale | Standard Deviation 4.11 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 | Week 48, n=211, 201 | 26.6 Scores on a scale | Standard Deviation 4.11 |
Secondary
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The treatment satisfaction score (range: 0-60) was the sum of the individual items. HIVTSQ mITT-E Population=Only participants from USA, France, Germany, Italy, Spain for whom valid translations were available from the mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
Time frame: Week 4, Week 24, and Week 48
Population: HIVTSQ mITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 4, n=206, 192 | 54.1 Scores on a scale | Standard Deviation 6.43 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 24, n= 211, 200 | 56.1 Scores on a scale | Standard Deviation 5.16 |
| DTG 50 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 48, n=212, 201 | 56.1 Scores on a scale | Standard Deviation 4.6 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 4, n=206, 192 | 52.4 Scores on a scale | Standard Deviation 7.94 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 24, n= 211, 200 | 54.3 Scores on a scale | Standard Deviation 6.94 |
| DRV 800 mg + RTV 100 mg QD | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 | Week 48, n=212, 201 | 54.5 Scores on a scale | Standard Deviation 6.78 |
Secondary
Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF)
An assessment was made of every change across all amino acids within the integrase (IN), reverse transcriptase (RT), and Protease (PRO) encoding region at Baseline and at time of suspected PDVF. PDVF is defined as the confirmed plasma HIV-1 RNA \>200 c/mL \>=Week 24. PDVF Genotypic Population included all participants in the mITT-E population with available on-treatment genotypic resistance data, at time of PDVF. Only those participants with data available at the specified time points were analyzed.
Time frame: Baseline until PDVF up to Week 48
Population: PDVF Genotypic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg QD | Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF) | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF) | 0 Participants |
Secondary
Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48
The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).
Time frame: Week 48
Population: mITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg QD | Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48 | 0 Participants |
Secondary
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities
Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred.
Time frame: From Baseline through Week 48
Population: mSafety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Alanine Amino Transferase, G3 | 2 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Alanine Amino Transferase, G4 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Aspartate Amino Transferase, G3 | 6 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Aspartate Amino Transferase, G4 | 2 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Cholesterol, G3 | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Creatine Kinase, G3 | 8 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Creatine Kinase, G4 | 8 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hyperglycaemia, G3 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hypoglycaemia, G3 | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | LDL Cholesterol, G3 | 2 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Lipase, G3 | 5 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Lipase, G4 | 2 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Phosphorus, inorganic, G3 | 7 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Bilirubin, G3 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Triglycerides, G3 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Triglycerides, G4 | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hemoglobin, G3 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hemoglobin, G4 | 1 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Platelet count, G4 | 0 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Neutrophils, G3 | 5 Participants |
| DTG 50 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Neutrophils, G4 | 3 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Lipase, G3 | 5 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Alanine Amino Transferase, G3 | 1 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Platelet count, G4 | 1 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Alanine Amino Transferase, G4 | 3 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Lipase, G4 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Aspartate Amino Transferase, G3 | 3 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hemoglobin, G3 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Aspartate Amino Transferase, G4 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Phosphorus, inorganic, G3 | 7 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Cholesterol, G3 | 3 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Neutrophils, G4 | 1 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Creatine Kinase, G3 | 5 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Bilirubin, G3 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Creatine Kinase, G4 | 4 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hemoglobin, G4 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hyperglycaemia, G3 | 2 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Triglycerides, G3 | 2 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Hypoglycaemia, G3 | 1 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Total Neutrophils, G3 | 0 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | LDL Cholesterol, G3 | 6 Participants |
| DRV 800 mg + RTV 100 mg QD | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities | Triglycerides, G4 | 1 Participants |
Secondary
Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48
Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for which an increase in fasting LDL cholesterol to Grade 2 or higher occurred. Only those participants with data available at the specified time points were analyzed.
Time frame: From Baseline through Week 48
Population: mSafety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg QD | Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48 | 2 Percentage of Participants |
| DRV 800 mg + RTV 100 mg QD | Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48 | 7 Percentage of Participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48
The percentage of participants with Plasma HIV-1 RNA \<400 c/mL at Week 48 was assessed MSDF, as codified by the FDA snapshot algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).
Time frame: Week 48
Population: mITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DTG 50 mg QD | Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48 | 92 Percentage of participants |
| DRV 800 mg + RTV 100 mg QD | Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48 | 87 Percentage of participants |
Secondary
Time to Virologic Suppression (<50 Copies/mL) Through Week 48
The time to viral suppression (i.e. first viral load value \<50 copies/mL) through Week 48 was derived and summarized using Kaplan-Meier plots. Participants who withdrew for any reason without having suppressed prior to the analysis were censored. Confidence intervals were estimated using the Brookmeyer-Crowley method.
Time frame: From Baseline through Week 48
Population: mITT-E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DTG 50 mg QD | Time to Virologic Suppression (<50 Copies/mL) Through Week 48 | 28.0 Days |
| DRV 800 mg + RTV 100 mg QD | Time to Virologic Suppression (<50 Copies/mL) Through Week 48 | 85.0 Days |