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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
724
Elvitegravir (EVG) tablet administered orally once daily with food
Raltegravir tablet administered orally twice daily according to prescribing information
Placebo to match elvitegravir administered orally once daily
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.
Southwest Center for HIV/AIDS
Phoenix, Arizona, United States
Health for Life Clinic, PLLC
Little Rock, Arkansas, United States
Pacific Oaks Medical Group
Beverly Hills, California, United States
AIDS Healthcare Foundation-Research Center
Beverly Hills, California, United States
Center for Special Immunology
Fountain Valley, California, United States
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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The Living Hope Foundation
Long Beach, California, United States
Kaiser Permanente
Los Angeles, California, United States
Jeffrey Goodman Special Care Clinic
Los Angeles, California, United States
University of Southern California, AIDS Clinical Trials Unit
Los Angeles, California, United States
Peter J. Ruane, MD, Inc.
Los Angeles, California, United States
...and 170 more locations