Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive Women

Phase 3

Completed

Conditions: Acquired Immunodeficiency Syndrome
HIV Infections

Interventions: Drug: E/C/F/TDF
Drug: RTV
Drug: ATV
Drug: ATV Placebo
Drug: FTC/TDF
Drug: RTV Placebo
Drug: FTC/TDF Placebo
Drug: E/C/F/TDF Placebo
Drug: E/C/F/TAF

Registration Number: NCT01705574

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objective of this study is to evaluate the efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in HIV-1 infected, antiretroviral treatment-naive adult women.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 583

Inclusion Criteria

Female (at birth), age ≥ 18 years
Ability to understand and sign a written informed consent form
Plasma HIV-1 RNA levels ≥ 500 copies/mL
No prior use of any approved or investigational antiretroviral drug for any length of time
Screening genotype report must show sensitivity to emtricitabine (FTC), tenofovir disoproxil fumarate (TDF) and atazanavir (ATV) boosted with ritonavir (RTV)
Normal ECG
Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
Hepatic transaminases ≤ 5 x upper limit of normal (ULN)
Total bilirubin ≤ 1.5 mg/dL
Adequate hematologic function
Serum amylase ≤ 5 x ULN
Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug
Women who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.

Key

Exclusion Criteria

A new AIDS defining condition diagnosed within the 30 days
Females receiving drug treatment for Hepatitis C, or females who are anticipated to receive treatment for Hepatitis C during the course of the study
Females experiencing decompensated cirrhosis
Females who are breastfeeding
Positive serum pregnancy test (female of childbearing potential)
Have an implanted defibrillator or pacemaker
Have an ECG pulse rate interval ≥ 220 msec
Current alcohol or substance use which may potentially interfere with the female's study compliance
History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
Participation in any other clinical trial without prior approval
Any other clinical condition or prior therapy that would make the female unsuitable for the study or unable to comply with the dosing requirements
Females receiving ongoing therapy with any disallowed medications, including drugs not to be used with elvitegravir, cobicistat, FTC, TDF, ATV, RTV; or females with any known allergies to the excipients of Stribild® tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATV + RTV+ FTC/TDF	RTV	ATV + RTV + FTC/TDF + E/C/F/TDF placebo
Open-Label Extension Phase	ATV	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
ATV + RTV+ FTC/TDF	FTC/TDF	ATV + RTV + FTC/TDF + E/C/F/TDF placebo
E/C/F/TDF	ATV Placebo	E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
E/C/F/TDF	E/C/F/TDF	E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
E/C/F/TDF	RTV Placebo	E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
E/C/F/TDF	FTC/TDF Placebo	E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
ATV + RTV+ FTC/TDF	ATV	ATV + RTV + FTC/TDF + E/C/F/TDF placebo
ATV + RTV+ FTC/TDF	E/C/F/TDF Placebo	ATV + RTV + FTC/TDF + E/C/F/TDF placebo
Open-Label Extension Phase	FTC/TDF	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
Open-Label Extension Phase	E/C/F/TAF	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
Open-Label Extension Phase	E/C/F/TDF	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
Open-Label Extension Phase	RTV	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm	Week 48	The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Secondary Outcome Measures

Name	Time	Method
Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase	Baseline; Open-Label Extension Week 48
Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase	Baseline; Week 48
Percentage of Participants Receiving STB or ATV+RTV+TVD With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase	Open-Label Extension Week 48	The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 of the open-label phase was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm	Week 96	The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Trial Locations

Locations (99): University of Southern California AIDS Clinical Trials Group
🇺🇸
Los Angeles, California, United States
University of California, Davis Medical Center
🇺🇸
Sacramento, California, United States
Whitman-Walker Health
🇺🇸
Washington, District of Columbia, United States
George Washington University Medical Faculty Associates
🇺🇸
Washington, District of Columbia, United States
Midway Immunology and Research Center
🇺🇸
Fort Pierce, Florida, United States
University of Miami
🇺🇸
Miami, Florida, United States
Orlando Immunology Center
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Orlando, Florida, United States
IDOCF/ValuhealthMD
🇺🇸
Orlando, Florida, United States
St. Joseph's Hospital Comprehensive Research Institute
🇺🇸
Tampa, Florida, United States
Triple O Research Institute, P.A.
🇺🇸
West Palm Beach, Florida, United States
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University of Southern California AIDS Clinical Trials Group
🇺🇸Los Angeles, California, United States