HIV Infection
Conditions
Keywords
HIV, HIV I, Treatment Experienced
Brief summary
The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily elvitegravir (EVG) versus twice-daily raltegravir (RAL) added to a background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or 2 additional antiretroviral (ARV) agents) in HIV-1 infected, ARV treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of ARV agents. Participants will be randomized in a 1:1 ratio to receive EVG plus background regimen (Elvitegravir group), or raltegravir plus background regimen (Raltegravir group). Due to known drug interactions, participants in the Elvitegravir group receiving RTV-boosted atazanavir (ATV) or RTV-boosted lopinavir (LPV) as part of their background regimen will receive elvitegravir at a lower dose (85 mg).
Detailed description
The background regimen will be constructed by the investigator based on viral resistance testing. The fully active PI will be defined by phenotypic resistance analysis. For phenotypic susceptibility, fully active is defined as being below the lower clinical or biological cutoff. Participants are required to take their ritonavir dose based on the dosing schedule indicated in the prescribing information for the PI; no additional ritonavir is required to be taken with EVG. No other marketed PIs are allowed as part of the background regimen due to unknown drug interactions. The second agent can be one nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), etravirine, maraviroc, or T-20. However, the second agent must not include an integrase inhibitor; the nonnucleoside reverse transcriptase inhibitors efavirenz, nevirapine, or delavirdine (due to unknown drug interactions); or the fixed-dose combination therapies Atripla® or Trizivir® (abacavir sulfate/lamivudine/zidovudine). The second agent may or may not be fully active (except in Spain, where participants have to receive a fully active second agent, as requested by the Spanish regulatory agency). If the M184V/I reverse transcriptase (RT) mutation is present on the screening genotype report and an NRTI is used as the second agent, then either FTC or LAM may be added as a third agent in the background regimen to maintain the M184V/I mutation. In this situation only, the fixed-dose combination therapies Combivir®, Truvada®, or Epzicom/Kivexa® may be prescribed as the combined second and third agents of the background regimen. After Week 96, participants will continue to take their blinded study drug and attend visits until treatment assignments are unblinded, at which point they will be given the option to participate in an open-label EVG extension phase of the study.
Interventions
DRUGElvitegravir
Elvitegravir (EVG) tablet administered orally once daily with food
DRUGRaltegravir
Raltegravir tablet administered orally twice daily according to prescribing information
DRUGEVG placebo
Placebo to match elvitegravir administered orally once daily
DRUGRAL placebo
RAL placebo administered orally twice daily.
Background Regimen (administered according to prescribing information) contains 1 fully-active ritonavir-boosted protease inhibitor (PI/r) plus 1 or 2 additional agents. The ritonavir-boosted PIs include either ATV, darunavir, fosamprenavir, LPV (Kaletra®), or tipranavir; the additional agents include abacavir (ABC), Combivir® (lamivudine (LAM)/zidovudine (ZDV) coformulated), didanosine, emtricitabine (FTC), enfuvirtide, Epzicom® (ABC/LAM coformulated), etravirine, LAM, maraviroc, tenofovir disoproxil fumarate (TDF), Truvada®, (FTC/TDF coformulated), and/or ZDV.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening * Documented resistance or at least six months experience prior to screening with two or more different classes of antiretroviral agents * Stable antiretroviral regimen for at least 30 days prior to screening: however, participants may discontinue the antiretroviral regimen after screening and remain off therapy until baseline at the discretion of the investigator * Eligible to receive one of the fully-active ritonavir-boosted-PIs, and an allowed second agent * Normal ECG * Adequate renal function (estimated glomerular filtration rate according to the Cockcroft-Gault formula ≥ 60 mL/min) * Hepatic transaminases ≤ 5 × upper limit of normal * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL) * Serum amylase \< 1.5 × the upper limit of the normal range * Negative serum pregnancy test (females of childbearing potential only) * Males and females of childbearing potential must agree to use highly effective contraception methods * Age ≥ 18 years * Life expectancy ≥ 1 year * Ability to understand and sign a written informed consent form
Exclusion criteria
* New AIDS-defining condition diagnosed within the 30 days prior to screening * Prior treatment with any HIV-1 integrase inhibitor * Participants experiencing ascites * Participants experiencing encephalopathy * Females who are breastfeeding * Positive serum pregnancy test at any time during the study (female of childbearing potential) * Participants receiving ongoing therapy with any disallowed medication * Current alcohol or substance use judged by the investigator to potentially interfere with study compliance * Malignancy other than cutaneous Kaposi's sarcoma or basal cell carcinoma * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline * Participation in any other clinical trial (except for the etravirine or maraviroc expanded access program), without prior approval from sponsor * Any other clinical condition or prior therapy that would make participants unsuitable for the study * Known hypersensitivity to study drug, metabolites or formulation excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 | Week 48 | The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA-defined Time to Loss of Virologic Response (TLOVR) algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48 | Week 48 | The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding. |
| Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96 | Week 96 | The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding. |
| Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL) | Week 48 | Virologic response at Week 48 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time. |
| Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL) | Week 96 | Virologic response at Week 96 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time. |
| Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48 | Baseline to Week 48 | The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis. |
| Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96 | Baseline to Week 96 | The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis. |
| Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48 | Baseline to Week 48 | The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis. |
| Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96 | Baseline to Week 96 | The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis. |
| Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96 | Week 96 | The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | Week 96 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the missing = failure method. |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | Week 48 | The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the missing = failure method. |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | Week 96 | The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the missing = failure method. |
| Change From Baseline in HIV-1 RNA at Week 48 | Baseline to Week 48 | The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 was analyzed. |
| Change From Baseline in HIV-1 RNA at Week 96 | Baseline to Week 96 | The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 96 was analyzed. |
| Change From Baseline in CD4 Cell Count at Week 48 | Baseline to Week 48 | The change from baseline in CD4 cell count (cells/mm\^3) at Week 48 was analyzed. |
| Change From Baseline in CD4 Cell Count at Week 96 | Baseline to Week 96 | The change from baseline in CD4 cell count (cells/mm\^3) at Week 96 was analyzed. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | Week 48 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the missing = failure method, where participants with missing data were considered as having failed to meet the criteria for evaluation. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Mexico, Netherlands, Portugal, Puerto Rico, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in a total of 161 study sites in Australia, Europe, and North America. The first participant was screened on 19 June 2008. The last study visit occurred on 22 April 2015.
Pre-assignment details
1335 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Elvitegravir EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase. | 354 |
| Raltegravir RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase. | 358 |
| Total | 712 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-Label Phase | Adverse Event | 1 | 2 |
| Open-Label Phase | Death | 3 | 1 |
| Open-Label Phase | Investigator's Discretion | 3 | 2 |
| Open-Label Phase | Lack of Efficacy | 7 | 4 |
| Open-Label Phase | Lost to Follow-up | 10 | 8 |
| Open-Label Phase | Other | 1 | 0 |
| Open-Label Phase | Participant Noncompliance | 7 | 7 |
| Open-Label Phase | Withdrew Consent | 12 | 6 |
| Randomized Phase | Adverse Event | 8 | 12 |
| Randomized Phase | Death | 2 | 9 |
| Randomized Phase | Investigator's Discretion | 7 | 10 |
| Randomized Phase | Lack of Efficacy | 14 | 19 |
| Randomized Phase | Lost to Follow-up | 34 | 34 |
| Randomized Phase | Participant Noncompliance | 40 | 32 |
| Randomized Phase | Pregnancy | 3 | 0 |
| Randomized Phase | Protocol Violation | 10 | 11 |
| Randomized Phase | Randomized but Not Treated | 7 | 5 |
| Randomized Phase | Withdrew Consent | 31 | 22 |
Baseline characteristics
| Characteristic | Total | Elvitegravir | Raltegravir |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 9.1 | 44 years STANDARD_DEVIATION 9 | 45 years STANDARD_DEVIATION 9.1 |
| Chronic Hepatitis B (HBV) Infection Status Indeterminant | 1 participants | 1 participants | 0 participants |
| Chronic Hepatitis B (HBV) Infection Status Negative | 675 participants | 333 participants | 342 participants |
| Chronic Hepatitis B (HBV) Infection Status No baseline HBV measurement | 6 participants | 3 participants | 3 participants |
| Chronic Hepatitis B (HBV) Infection Status Positive | 30 participants | 17 participants | 13 participants |
| Chronic Hepatitis C (HCV) Infection Status Indeterminant | 4 participants | 2 participants | 2 participants |
| Chronic Hepatitis C (HCV) Infection Status Negative | 603 participants | 305 participants | 298 participants |
| Chronic Hepatitis C (HCV) Infection Status No baseline HCV measurement | 6 participants | 3 participants | 3 participants |
| Chronic Hepatitis C (HCV) Infection Status Positive | 99 participants | 44 participants | 55 participants |
| Cluster of differentiation (CD4) Cell Count | 261.6 cells/mm^3 STANDARD_DEVIATION 205.57 | 257.9 cells/mm^3 STANDARD_DEVIATION 204.31 | 265.3 cells/mm^3 STANDARD_DEVIATION 207.04 |
| Enfuvirtide (T-20) in background regimen No | 709 participants | 352 participants | 357 participants |
| Enfuvirtide (T-20) in background regimen Yes | 3 participants | 2 participants | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 155 Participants | 81 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 555 Participants | 272 Participants | 283 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Etravirine in background regimen No | 612 participants | 309 participants | 303 participants |
| Etravirine in background regimen Yes | 100 participants | 45 participants | 55 participants |
| HIV-1 RNA | 4.26 log10 copies/mL STANDARD_DEVIATION 0.955 | 4.26 log10 copies/mL STANDARD_DEVIATION 0.969 | 4.27 log10 copies/mL STANDARD_DEVIATION 0.943 |
| HIV-1 RNA category ≤ 100,000 copies/mL | 530 participants | 263 participants | 267 participants |
| HIV-1 RNA category > 100,000 copies/mL | 182 participants | 91 participants | 91 participants |
| HIV Disease Status AIDS | 251 participants | 126 participants | 125 participants |
| HIV Disease Status Asymptomatic | 347 participants | 172 participants | 175 participants |
| HIV Disease Status Symptomatic HIV Infections | 106 participants | 52 participants | 54 participants |
| HIV Disease Status Unknown | 8 participants | 4 participants | 4 participants |
| Maraviroc in background regimen No | 670 participants | 330 participants | 340 participants |
| Maraviroc in background regimen Yes | 42 participants | 24 participants | 18 participants |
| Phenotypic Sensitivity Score 1.0 | 9 participants | 5 participants | 4 participants |
| Phenotypic Sensitivity Score 1.5 | 51 participants | 23 participants | 28 participants |
| Phenotypic Sensitivity Score 2.0 | 622 participants | 309 participants | 313 participants |
| Phenotypic Sensitivity Score 2.5 | 3 participants | 2 participants | 1 participants |
| Phenotypic Sensitivity Score 3.0 | 24 participants | 14 participants | 10 participants |
| Phenotypic Sensitivity Score 3.5 | 1 participants | 0 participants | 1 participants |
| Phenotypic Sensitivity Score No baseline PSS score | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 6 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 14 participants | 9 participants | 5 participants |
| Race/Ethnicity, Customized Black or African American | 247 participants | 128 participants | 119 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 7 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized White | 437 participants | 210 participants | 227 participants |
| Region of Enrollment Australia | 29 participants | 17 participants | 12 participants |
| Region of Enrollment Belgium | 11 participants | 5 participants | 6 participants |
| Region of Enrollment Canada | 34 participants | 16 participants | 18 participants |
| Region of Enrollment France | 25 participants | 16 participants | 9 participants |
| Region of Enrollment Germany | 14 participants | 6 participants | 8 participants |
| Region of Enrollment Italy | 17 participants | 7 participants | 10 participants |
| Region of Enrollment Mexico | 51 participants | 26 participants | 25 participants |
| Region of Enrollment Netherlands | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Portugal | 21 participants | 10 participants | 11 participants |
| Region of Enrollment Puerto Rico | 22 participants | 8 participants | 14 participants |
| Region of Enrollment Spain | 34 participants | 14 participants | 20 participants |
| Region of Enrollment United Kingdom | 11 participants | 6 participants | 5 participants |
| Region of Enrollment United States | 453 participants | 230 participants | 223 participants |
| Sex: Female, Male Female | 127 Participants | 60 Participants | 67 Participants |
| Sex: Female, Male Male | 585 Participants | 294 Participants | 291 Participants |
| Type of NRTI in Background Regimen abacavir | 21 participants | 6 participants | 15 participants |
| Type of NRTI in Background Regimen abacavir/lamivudine | 12 participants | 4 participants | 8 participants |
| Type of NRTI in Background Regimen didanosine | 8 participants | 1 participants | 7 participants |
| Type of NRTI in Background Regimen emtricitabine | 5 participants | 2 participants | 3 participants |
| Type of NRTI in Background Regimen emtricitabine/tenofovir disoproxil fumarate | 157 participants | 91 participants | 66 participants |
| Type of NRTI in Background Regimen lamivudine | 26 participants | 13 participants | 13 participants |
| Type of NRTI in Background Regimen lamivudine/zidovudine | 11 participants | 6 participants | 5 participants |
| Type of NRTI in Background Regimen no NRTI in background regimen | 129 participants | 65 participants | 64 participants |
| Type of NRTI in Background Regimen tenofovir disoproxil fumarate | 334 participants | 163 participants | 171 participants |
| Type of NRTI in Background Regimen zidovudine | 9 participants | 3 participants | 6 participants |
| Type of PI in Background Regimen (Excluding Ritonavir) atazanavir | 117 participants | 64 participants | 53 participants |
| Type of PI in Background Regimen (Excluding Ritonavir) darunavir | 408 participants | 202 participants | 206 participants |
| Type of PI in Background Regimen (Excluding Ritonavir) fosamprenavir | 34 participants | 14 participants | 20 participants |
| Type of PI in Background Regimen (Excluding Ritonavir) lopinavir | 140 participants | 68 participants | 72 participants |
| Type of PI in Background Regimen (Excluding Ritonavir) tipranavir | 13 participants | 6 participants | 7 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 279 / 354 | 250 / 358 | 394 / 505 |
| serious Total, serious adverse events | 73 / 354 | 86 / 358 | 127 / 505 |
Outcome results
Primary
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48
The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA-defined Time to Loss of Virologic Response (TLOVR) algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 | 59.0 percentage of participants |
| Raltegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 | 57.8 percentage of participants |
Comparison: The planned sample size of 700 HIV-1 infected participants, (350 in each group) was estimated to provide at least 85% power to establish noninferiority in the percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL through Week 48. For sample size and power computation, it was assumed that both elvitegravir and raltegravir arms have a response rate of 0.74, that a noninferiority margin was 0.10, and that the significance level of the test was 1-sided 0.025 level.95% CI: [-6, 8.2]
Secondary
Change From Baseline in CD4 Cell Count at Week 48
The change from baseline in CD4 cell count (cells/mm\^3) at Week 48 was analyzed.
Time frame: Baseline to Week 48
Population: Participants in the ITT Analysis Set with evaluable change data at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elvitegravir | Change From Baseline in CD4 Cell Count at Week 48 | 138 cells/mm^3 | Standard Deviation 141.4 |
| Raltegravir | Change From Baseline in CD4 Cell Count at Week 48 | 147 cells/mm^3 | Standard Deviation 148.9 |
95% CI: [-33, 16]
Secondary
Change From Baseline in CD4 Cell Count at Week 96
The change from baseline in CD4 cell count (cells/mm\^3) at Week 96 was analyzed.
Time frame: Baseline to Week 96
Population: Participants in the ITT Analysis Set with evaluable change data at Week 96 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elvitegravir | Change From Baseline in CD4 Cell Count at Week 96 | 205 cells/mm^3 | Standard Deviation 191.5 |
| Raltegravir | Change From Baseline in CD4 Cell Count at Week 96 | 198 cells/mm^3 | Standard Deviation 162.2 |
95% CI: [-25, 39]
Secondary
Change From Baseline in HIV-1 RNA at Week 48
The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 was analyzed.
Time frame: Baseline to Week 48
Population: Participants in the ITT Analysis Set with evaluable change data at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elvitegravir | Change From Baseline in HIV-1 RNA at Week 48 | -2.17 log10 copies/mL | Standard Deviation 1.162 |
| Raltegravir | Change From Baseline in HIV-1 RNA at Week 48 | -2.18 log10 copies/mL | Standard Deviation 1.178 |
95% CI: [-0.16, 0.19]
Secondary
Change From Baseline in HIV-1 RNA at Week 96
The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 96 was analyzed.
Time frame: Baseline to Week 96
Population: Participants in the ITT Analysis Set with evaluable change data at Week 96 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elvitegravir | Change From Baseline in HIV-1 RNA at Week 96 | -2.26 log10 copies/mL | Standard Deviation 1.078 |
| Raltegravir | Change From Baseline in HIV-1 RNA at Week 96 | -2.31 log10 copies/mL | Standard Deviation 1.068 |
95% CI: [-0.12, 0.22]
Secondary
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48
The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48 | 68.1 percentage of participants |
| Raltegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48 | 67.2 percentage of participants |
95% CI: [-6, 7.7]
Secondary
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96
The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
Time frame: Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96 | 57.0 percentage of participants |
| Raltegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96 | 56.1 percentage of participants |
95% CI: [-6.4, 8.2]
Secondary
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96
The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
Time frame: Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96 | 47.6 percentage of participants |
| Raltegravir | Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96 | 45.0 percentage of participants |
95% CI: [-4.6, 9.9]
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the missing = failure method.
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 70.1 percentage of participants |
| Raltegravir | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 72.1 percentage of participants |
95% CI: [-8.6, 4.7]
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96
The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the missing = failure method.
Time frame: Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | 61.3 percentage of participants |
| Raltegravir | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | 63.0 percentage of participants |
95% CI: [-8.8, 5.5]
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the missing = failure method, where participants with missing data were considered as having failed to meet the criteria for evaluation.
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 61.0 percentage of participants |
| Raltegravir | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 60.7 percentage of participants |
95% CI: [-6.9, 7.3]
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the missing = failure method.
Time frame: Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 53.6 percentage of participants |
| Raltegravir | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 56.4 percentage of participants |
95% CI: [-10.2, 4.4]
Secondary
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48
The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.
Time frame: Baseline to Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48 | 24 percentage of participants |
| Raltegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48 | 24 percentage of participants |
Secondary
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96
The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.
Time frame: Baseline to Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96 | 32 percentage of participants |
| Raltegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96 | 31 percentage of participants |
Secondary
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48
The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.
Time frame: Baseline to Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48 | 35 percentage of participants |
| Raltegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48 | 35 percentage of participants |
Secondary
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96
The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.
Time frame: Baseline to Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96 | 45 percentage of participants |
| Raltegravir | Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96 | 46 percentage of participants |
Secondary
Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL)
Virologic response at Week 48 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL) | 59.8 percentage of participants |
| Raltegravir | Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL) | 57.5 percentage of participants |
95% CI: [-5, 9.3]
Secondary
Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL)
Virologic response at Week 96 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.
Time frame: Week 96
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elvitegravir | Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL) | 52.4 percentage of participants |
| Raltegravir | Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL) | 53.0 percentage of participants |
95% CI: [-7.9, 6.8]