Infection, Human Immunodeficiency Virus
Conditions
Keywords
GSK1349572, resistance to raltegravir or elvitegravir, Integrase inhibitor, ART-experienced, dolutegravir
Brief summary
The purpose of this trial is to assess the antiviral activity and safety of a dolutegravir (DTG) containing regimen in HIV-1 infected, antiretroviral therapy (ART)-experienced adults with current or historical failure on an integrase inhibitor (INI) containing regimen. The study will assess DTG 50mg twice daily administered initially with the current failing ART regimen but then with an optimised background ART regimen (OBR) after Day 7. The first analyses will be conducted after the last subject enrolled has completed 24 weeks. Subjects may remain on study after Week 24.
Detailed description
ING112574 is a Phase 3, multicentre, open-label, single arm study to assess the antiviral activity and safety of DTG containing regimen in HIV-1 infected ART-experienced adults with historical or current evidence of resistance to RAL or ELV. Initially, a minimum of 100 subjects will be enrolled to receive DTG 50mg twice daily with the current failing regimen for 7 days but with OBR from Day 8. Subjects must also have documented genotypic and/or phenotypic resistance to at least one compound in two or more of the other approved classes of ART but must also be able to include at least one fully active drug in the OBR to be started Day 8. The first data cut will take place after the (approximate) 100th subject enrolled completes the Week 24 visit. Enrollment will continue until a further 50 to 100 subjects have been recruited. All subjects who successfully complete 24 weeks of treatment will continue to have access to DTG until it is locally available as long as they continue to derive clinical benefit. ViiV Healthcare is the sponsor of this study.
Interventions
DRUGdolutegravir
50 mg twice daily
Sponsors
Shionogi
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Screening plasma HIV-1 RNA ≥500 copies/mL * ART-experienced, INI-experienced, DTG naïve * Experienced virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen * The subject's HIV-1 shows resistance to RAL or ELV at Screening or at prior time point of virological failure on RAL or ELV * Documented resistance to at least one drug from each of three or more of all approved classes of ART * Be able to receive at least one fully active drug as part of the OBR from Day 8 * Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol) * Willing and able to understand and provide signed and dated written informed consent prior to Screening.
Exclusion criteria
* Women who are pregnant or breast feeding * An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ \<200c/mm3) * Moderate to severe hepatic impairment as defined by Child-Pugh classification * Anticipated need for HCV therapy during the first 24 weeks of the study * Recent history of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding * Allergy or intolerance to the study drugs or their components or drugs of their class * Malignancy within the past 6 months * Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening * Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening * Treatment with any agent, other than licensed ART, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product * Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine may be used if coadministered with lopinivir/ritonavir or darunavir/ritonavir) * Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within 28 days prior to Screening * Verified Grade 4 laboratory abnormality at Screening * ALT\> 5 times the upper limit of normal (ULN) at Screening * ALT ≥ 3X ULN and bilirubin \> 1.5 X ULN (with 35% direct bilirubin) at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 | Baseline and Day 8 | Mean change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 was calculated as the Day 8 value minus the Baseline value. The last observation was carried forward if a participant had missed the Day 8 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 8. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 8. |
| Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24 | Week 24 | The number of participants who had viral load \<50 copies/mL at Week 24 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window. |
| Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48 | Week 48 | The number of participants who had viral load \<50 copies/mL at Week 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window. |
| Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. |
| Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to the DAIDS grading scale. The DAIDS displays events as Grades 1-4 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, potentially life threatening. |
| Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | The severity of clinical chemistry toxicities was graded according to the DAIDS toxicity scale. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity. |
| Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | The severity of hematology toxicities was graded according to the DAIDS. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | 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). |
| Cmax and Ctau of DTG | Day 8, Week 4, and Week 24 | The maximum plasma concentration (Cmax) and the concentration at the end of a dosing interval (Ctau) of DTG were assessed by a population pharmacokinetic (PK) modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24. |
| C0 Assessment of DTG | Day 8, Week 4, and Week 24 | The plasma DTG concentration immediately prior to dosing at steady state (C0) was assessed at Day 8, Week 4, and Week 24. Blood samples for pharmacokinetic assessments were collected pre-dose and 1-3 hours post-dose on Day 8 and at Week 4 and 4-12 hours post-dose at Week 24. Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Parameter Population. |
| Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | An analysis of changes at specific amino acids in the IN coding region associated with resistance to raltegravir, elvitegravir, or DTG was performed at Day 1 and at the time of PDVF. PDVF is a \<0.5 log10 copies(c)/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is \<400 c/mL. PDVF after Day 8 is defined as virological non-respones (decrease in plasma HIV-1 RNA of \<1 log10 c/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA \<400 c/mL and confirmed plasma HIV-1 RNA levels \>=400 c/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to \>=400 c/mL after prior confirmed suppression to \<400 c/mL and confirmed plasma HIV-1 RNA levels \>1 log10 c/mL above the nadir value \[nadir: \>=400 c/mL\]). |
| Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days) | 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. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF is defined as a \<0.5 log10 copies/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is \<400 copies/mL. PDVF after Day 8 was defined for virological non-response (decrease in plasma HIV-1 RNA of less than 1 log10 copies/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA \<400 copies/mL and confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL and confirmed plasma HIV-1 RNA levels \>1 log10 copies/mL above the nadir value, where nadir is \>=400 copies/mL). |
| AUC(0-tau) and AUC(0-24) of DTG | Day 8, Week 4, and Week 24 | The area under the time concentration curve over the dosing interval (AUC\[0-tau\]) and from 0 to 24 hours (AUC\[0-24\]) of DTG was assessed by a population PK modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24. |
| Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40 and 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the par. was on treatment within the VOI analysis window |
| Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | From Week 48 every 12 weeks up to study completion. | The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL was assessed at Weeks 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 using data of observed cases. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). |
| Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study completion (Up to Week 180) | Mean change from Baseline in plasma HIV-1 RNA was assesseed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48 , 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 using data of the observed cases. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | Absolute values for CD4+ cell counts were assessed at Baseline, Day 8 and Weeks 4, 8, 12, 16, and 24, and absolute values for CD8+ cell counts were assessed at Baseline and Weeks 4, 12, 24, and 48. |
| Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180. v | Median change from Baseline in CD4+ cell counts was assessed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Baseline; Weeks 4, 12, 24, and 48 | The ratio of CD4+/CD8+ cell count (measured in cells/mm\^3) was assessed at Baseline and at Weeks 4, 12, 24, and 48. The ratio was calculated as the CD4+ cell count divided by CD8+ cell count. |
Countries
Belgium, Canada, France, Italy, Portugal, Spain, United States
Participant flow
Recruitment details
Participants (par.) having documented Human immunodeficiency virus type 1 (HIV-1) infection with a plasma HIV-1 Ribonucleic acid(RNA) \>=500 copies per milliliter (c/mL) at Screening, Antiretroviral therapy (ART)-experienced and on stable ART for at least one month prior to Screening were enrolled
Pre-assignment details
A total of 139 par. were screen failures and 183 par. entered the single arm, open-label study.
Participants by arm
| Arm | Count |
|---|---|
| Dolutegravir 50 mg BID Participants received DTG 50 mg BID. | 183 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 27 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Dolutegravir 50 mg BID |
|---|---|
| Age, Continuous | 48 Years |
| Race/Ethnicity, Customized African American/African Heritage | 49 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native and White | 1 participants |
| Race/Ethnicity, Customized Asian-Central/South Asian Heritage | 1 participants |
| Race/Ethnicity, Customized White | 130 participants |
| Race/Ethnicity, Customized White and African American/African Heritage | 2 participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 143 / 183 |
| serious Total, serious adverse events | 46 / 183 |
Outcome results
Primary
Mean Change From Baseline in Plasma HIV-1 RNA at Day 8
Mean change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 was calculated as the Day 8 value minus the Baseline value. The last observation was carried forward if a participant had missed the Day 8 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 8. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 8.
Time frame: Baseline and Day 8
Population: Intent-to-Treat-Exposed (ITT-E) Population: all participants who received at least one dose of study drug. Only participants who had Day 8 observations were considered for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 | -1.432 log10 copies/milliliter (mL) | Standard Deviation 0.607 |
p-value: <0.00195% CI: [-1.52, -1.343]t-test, 2 sided
Primary
Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to the DAIDS grading scale. The DAIDS displays events as Grades 1-4 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, potentially life threatening.
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale | Grade 1 | 45 participants |
| Dolutegravir 50 mg BID | Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale | Grade 2 | 64 participants |
| Dolutegravir 50 mg BID | Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale | Grade 3 | 44 participants |
| Dolutegravir 50 mg BID | Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale | Grade 4 | 16 participants |
Primary
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: Safety Population: all participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) | Any AE | 169 participants |
| Dolutegravir 50 mg BID | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) | Any SAE | 46 participants |
Primary
Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24
The number of participants who had viral load \<50 copies/mL at Week 24 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
Time frame: Week 24
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24 | 126 participants |
95% CI: [62, 76]
Primary
Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
The number of participants who had viral load \<50 copies/mL at Week 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
Time frame: Week 48
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48 | 116 participants |
95% CI: [56, 70]
Primary
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade
The severity of clinical chemistry toxicities was graded according to the DAIDS toxicity scale. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade | Grade 1 | 49 participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade | Grade 2 | 67 participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade | Grade 3 | 43 participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade | Grade 4 | 16 participants |
Primary
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade
The severity of hematology toxicities was graded according to the DAIDS. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade | Grade 1 | 31 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade | Grade 2 | 15 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade | Grade 3 | 4 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade | Grade 4 | 2 Participants |
Secondary
Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48
Absolute values for CD4+ cell counts were assessed at Baseline, Day 8 and Weeks 4, 8, 12, 16, and 24, and absolute values for CD8+ cell counts were assessed at Baseline and Weeks 4, 12, 24, and 48.
Time frame: Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Population: ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Baseline, n=183 | 140.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.607 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Day 8, n=181 | 170.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.885 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 4, n=178 | 185.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.987 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 8, n=178 | 210.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 1.069 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 12, n=171 | 210.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 1.005 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 16, n=165 | 210.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 1.023 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 24, n=163 | 250.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.926 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 32, n=147 | 270.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.955 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 40, n=143 | 290.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.981 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD4+, Week 48, n=145 | 310.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.928 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD8+, Week 4, n=181 | 860.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.941 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD8+, Week 4, n=176 | 970.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.996 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD8+, Week 12, n=170 | 1015.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 1.008 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD8+, Week 24, n=154 | 1020.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.966 |
| Dolutegravir 50 mg BID | Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 | CD8+, Week 48, n=140 | 1000.0 Cells per millimeters cubed (cells/mm^3) | Inter-Quartile Range 0.904 |
Secondary
AUC(0-tau) and AUC(0-24) of DTG
The area under the time concentration curve over the dosing interval (AUC\[0-tau\]) and from 0 to 24 hours (AUC\[0-24\]) of DTG was assessed by a population PK modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24.
Time frame: Day 8, Week 4, and Week 24
Population: The Pharmacokinetic (PK) Concentration Population: all subjects who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dolutegravir 50 mg BID | AUC(0-tau) and AUC(0-24) of DTG | AUC(0-tau) | 36.7 µg*hour/mL | 95% Confidence Interval 91 |
| Dolutegravir 50 mg BID | AUC(0-tau) and AUC(0-24) of DTG | AUC(0-24) | 73.5 µg*hour/mL | 95% Confidence Interval 113 |
Secondary
C0 Assessment of DTG
The plasma DTG concentration immediately prior to dosing at steady state (C0) was assessed at Day 8, Week 4, and Week 24. Blood samples for pharmacokinetic assessments were collected pre-dose and 1-3 hours post-dose on Day 8 and at Week 4 and 4-12 hours post-dose at Week 24. Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Parameter Population.
Time frame: Day 8, Week 4, and Week 24
Population: Pharmacokinetic (PK) Parameter Population: all participants who received DTG, underwent PK sampling during the study, and provided an evaluable estimate of C0. Only participants with data available at the indicated time points were considered for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dolutegravir 50 mg BID | C0 Assessment of DTG | Day 8, n=148 | 2.36 µg/mL | Geometric Coefficient of Variation 91 |
| Dolutegravir 50 mg BID | C0 Assessment of DTG | Week 4, n=161 | 1.90 µg/mL | Geometric Coefficient of Variation 113 |
| Dolutegravir 50 mg BID | C0 Assessment of DTG | Week 24, n=135 | 2.14 µg/mL | Geometric Coefficient of Variation 93 |
Secondary
Cmax and Ctau of DTG
The maximum plasma concentration (Cmax) and the concentration at the end of a dosing interval (Ctau) of DTG were assessed by a population pharmacokinetic (PK) modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24.
Time frame: Day 8, Week 4, and Week 24
Population: The Pharmacokinetic (PK) Concentration Population: all subjects who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Cmax and Ctau of DTG | Cmax | 4.74 Micrograms per milliliter (µg/mL) |
| Dolutegravir 50 mg BID | Cmax and Ctau of DTG | Ctau | 2.60 Micrograms per milliliter (µg/mL) |
Secondary
Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion
Mean change from Baseline in plasma HIV-1 RNA was assesseed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48 , 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 using data of the observed cases. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study completion (Up to Week 180)
Population: ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Day 8, n=182 | -1.432 Log10 copies/mL | Standard Deviation 0.607 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 4, n=180 | -2.088 Log10 copies/mL | Standard Deviation 0.885 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 8, n=179 | -2.101 Log10 copies/mL | Standard Deviation 0.987 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 12, n=174 | -2.113 Log10 copies/mL | Standard Deviation 1.069 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 16, n=165 | -2.216 Log10 copies/mL | Standard Deviation 1.005 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 24, n=164 | -2.211 Log10 copies/mL | Standard Deviation 1.023 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 32, n=146 | -2.373 Log10 copies/mL | Standard Deviation 0.926 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 40, n=144 | -2.301 Log10 copies/mL | Standard Deviation 0.955 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 48, n=146 | -2.321 Log10 copies/mL | Standard Deviation 0.981 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 60, n=142 | -2.356 Log10 copies/mL | Standard Deviation 0.928 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 72, n=138 | -2.390 Log10 copies/mL | Standard Deviation 0.941 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 84, n=138 | -2.311 Log10 copies/mL | Standard Deviation 0.996 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 96, n=120 | -2.346 Log10 copies/mL | Standard Deviation 1.008 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 108, n=98 | -2.394 Log10 copies/mL | Standard Deviation 0.966 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 120, n=82 | -2.515 Log10 copies/mL | Standard Deviation 0.904 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 132, n=61 | -2.456 Log10 copies/mL | Standard Deviation 0.988 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 144, n=45 | -2.585 Log10 copies/mL | Standard Deviation 0.983 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 156, n=32 | -2.595 Log10 copies/mL | Standard Deviation 1.009 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 168, n=24 | -2.719 Log10 copies/mL | Standard Deviation 0.898 |
| Dolutegravir 50 mg BID | Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion | Week 180, n=6 | -2.425 Log10 copies/mL | Standard Deviation 1.557 |
Secondary
Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion
Median change from Baseline in CD4+ cell counts was assessed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180. v
Population: ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Day 8, n=181 | 20.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 4, n=178 | 30.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 8, n=178 | 40.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 12, n=171 | 50.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 16, n=165 | 60.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 24, n=163 | 61.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 32, n=147 | 100.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 40, n=143 | 90.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 48, n=145 | 110.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 60, n=142 | 120.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 72, n=138 | 140.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 84, n=137 | 150.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 96, n=117 | 160.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 108, n=98 | 180.5 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 120, n=82 | 180.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 132, n=61 | 221.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 144, n=46 | 205.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week 156, n=32 | 225.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week168, n=24 | 265.0 Cells per millimeters cubed (cells/mm^3) |
| Dolutegravir 50 mg BID | Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion | CD4+, Week180, n=6 | 170.5 Cells per millimeters cubed (cells/mm^3) |
Secondary
Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death)
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: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) | Progression from CDC Class A to Class C Event | 1 Participants |
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) | Progression from CDC Class B to Class C Event | 2 Participants |
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) | Progression from CDC Class C to New Class C Event | 6 Participants |
| Dolutegravir 50 mg BID | Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) | Progression from Classes A, B, or C to Death | 2 Participants |
Secondary
Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40 and 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the par. was on treatment within the VOI analysis window
Time frame: Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Baseline | 1 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Day 8 | 28 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 4 | 98 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 8 | 112 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 12 | 116 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 16 | 116 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 24 | 126 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 32 | 117 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 40 | 108 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <50 c/mL, Week 48 | 116 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Baseline | 8 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Day 8 | 82 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 4 | 145 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 8 | 146 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 12 | 142 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 16 | 139 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 24 | 135 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 32 | 127 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 40 | 119 participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 | HIV-1 RNA <400 c/mL, Week 48 | 125 participants |
Secondary
Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion
The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL was assessed at Weeks 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 using data of observed cases. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: From Week 48 every 12 weeks up to study completion.
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 48, n =146 | 121 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 60, n=142 | 110 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 72, n=138 | 116 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 84, n=138 | 108 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 96, n=120 | 101 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 108, n=98 | 81 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 120, n=82 | 72 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 132, n=61 | 49 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 144, n=45 | 37 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 156, n=32 | 28 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 168, n=24 | 20 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <50 c/mL, Week 180, n=6 | 4 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 48, n=146 | 134 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 60, n=142 | 131 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 72, n=138 | 130 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 84, n=138 | 127 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 96, n=120 | 111 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 108, n=98 | 92 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 120, n=82 | 80 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 132, n=61 | 59 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 144, n=45 | 44 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 156, n=32 | 31 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 168, n=24 | 23 Participants |
| Dolutegravir 50 mg BID | Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion | HIV-1 RNA <400 c/mL, Week 180, n=6 | 5 Participants |
Secondary
Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and 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. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF is defined as a \<0.5 log10 copies/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is \<400 copies/mL. PDVF after Day 8 was defined for virological non-response (decrease in plasma HIV-1 RNA of less than 1 log10 copies/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA \<400 copies/mL and confirmed plasma HIV-1 RNA levels \>=400 copies/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to \>=400 copies/mL after prior confirmed suppression to \<400 copies/mL and confirmed plasma HIV-1 RNA levels \>1 log10 copies/mL above the nadir value, where nadir is \>=400 copies/mL).
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: PDVF Phenotypic Resistance Populations. Only participants with Baseline DTG IC50 with PDVF who had paired Baseline and time of virological failure samples were considered for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | <1 fold | 6 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 1-<2 fold | 16 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 2-<4 fold | 4 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | 4-<8 fold | 4 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | >=8 fold | 12 Participants |
| Dolutegravir 50 mg BID | Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance | Missing | 3 Participants |
Secondary
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance
An analysis of changes at specific amino acids in the IN coding region associated with resistance to raltegravir, elvitegravir, or DTG was performed at Day 1 and at the time of PDVF. PDVF is a \<0.5 log10 copies(c)/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is \<400 c/mL. PDVF after Day 8 is defined as virological non-respones (decrease in plasma HIV-1 RNA of \<1 log10 c/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA \<400 c/mL and confirmed plasma HIV-1 RNA levels \>=400 c/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to \>=400 c/mL after prior confirmed suppression to \<400 c/mL and confirmed plasma HIV-1 RNA levels \>1 log10 c/mL above the nadir value \[nadir: \>=400 c/mL\]).
Time frame: From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Population: PDVF Genotypic Resistance Populations: all participants in the ITT-E Population with available on-treatment genotypic resistance data at the time of PDVF. Only participants with Baseline IN mutations with PDVF who had paired Baseline and time of PDVF samples were considered for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dolutegravir 50 mg BID | 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 | Any IN mutation | 25 participants |
| Dolutegravir 50 mg BID | 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 | T97A | 8 participants |
| Dolutegravir 50 mg BID | 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 | T97T/A | 4 participants |
| Dolutegravir 50 mg BID | 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 | E138A | 1 participants |
| Dolutegravir 50 mg BID | 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 | E138E/A | 1 participants |
| Dolutegravir 50 mg BID | 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 | E138E/K | 3 participants |
| Dolutegravir 50 mg BID | 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 | E138K | 4 participants |
| Dolutegravir 50 mg BID | 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 | E138T/A | 1 participants |
| Dolutegravir 50 mg BID | 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 | N155H | 6 participants |
| Dolutegravir 50 mg BID | 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 | N155N/H | 1 participants |
| Dolutegravir 50 mg BID | 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 | Q148H | 3 participants |
| Dolutegravir 50 mg BID | 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 | Q148Q/H | 2 participants |
| Dolutegravir 50 mg BID | 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 | Q148R | 1 participants |
| Dolutegravir 50 mg BID | 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 | Q148Q/R/K | 1 participants |
| Dolutegravir 50 mg BID | 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 | G140G/S | 1 participants |
| Dolutegravir 50 mg BID | 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 | G140S | 3 participants |
| Dolutegravir 50 mg BID | 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 | L74L/M/V | 1 participants |
| Dolutegravir 50 mg BID | 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 | L74L/M | 1 participants |
| Dolutegravir 50 mg BID | 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 | L74I | 1 participants |
| Dolutegravir 50 mg BID | 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 | E92E/Q | 2 participants |
| Dolutegravir 50 mg BID | 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 | S147G | 2 participants |
| Dolutegravir 50 mg BID | 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 | E157E/Q | 1 participants |
| Dolutegravir 50 mg BID | 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 | V151V/M/I | 1 participants |
| Dolutegravir 50 mg BID | 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 | Y143Y/H | 1 participants |
Secondary
Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48
The ratio of CD4+/CD8+ cell count (measured in cells/mm\^3) was assessed at Baseline and at Weeks 4, 12, 24, and 48. The ratio was calculated as the CD4+ cell count divided by CD8+ cell count.
Time frame: Baseline; Weeks 4, 12, 24, and 48
Population: ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dolutegravir 50 mg BID | Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Baseline, n=180 | 0.15 ratio |
| Dolutegravir 50 mg BID | Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Week 4, n=176 | 0.19 ratio |
| Dolutegravir 50 mg BID | Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Week 12, n=170 | 0.21 ratio |
| Dolutegravir 50 mg BID | Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Week 24, n=154 | 0.26 ratio |
| Dolutegravir 50 mg BID | Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 | Week 48, n=140 | 0.32 ratio |