Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment
- Conditions
- HCV InfectionHIV-1 Infection
- Interventions
- Registration Number
- NCT02707601
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 150
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Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/- ribavirin (RBV) +/- HCV protease inhibitor (PI).
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Compensated cirrhotic individuals must be HCV treatment-naive.
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No prior treatments with NS5A and NS5B or any HCV direct acting antivirals, except boceprevir, telaprevir and simeprevir, in combination with IFN and RBV
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Currently on an ARV regimen (2 NRTI + a third agent) without change for 6 months prior to screening.
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Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values ("blips") of HIV-1 RNA ≥ 50 copies/mL followed by resuppression is allowed.
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For individuals with 3 or more prior ARV regimens, a regimen history should be provided for approval by the Sponsor.
- Note: Individuals that changed from TDF to TAF less than 6 months ago will be eligible as long as the TDF/ TAF change was the only change to the regimen.
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Plasma HIV-1 RNA level < 50 copies/mL at the screening visit
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Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype prior to first ARV is not available or individual had 3 or more prior ARV regimens, individual will have proviral genotype analysis for archived resistance prior to Day 1.
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No history of HIV virologic failure
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No evidence of Hepatitis B infection
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Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min as estimated by Cockcroft-Gault formula
Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description E/C/F/TAF + LDV/SOF E/C/F/TAF Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. E/C/F/TAF + LDV/SOF LDV/SOF Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. F/R/TAF + LDV/SOF LDV/SOF Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. F/R/TAF + LDV/SOF F/R/TAF Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12) HCV Posttreatment Week 12 Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm 24 weeks after start of HIV treatment The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were 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 HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4) HCV Posttreatment Week 4 SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping LDV/SOF treatment.
Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment Up to 32 weeks plus 30 days
Trial Locations
- Locations (42)
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Peter Shalit MD
🇺🇸Seattle, Washington, United States
University of Miami
🇺🇸Miami, Florida, United States
Therafirst Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
Whitman-Walker Health
🇺🇸Washington, District of Columbia, United States
Midway Immunology & Research Center, LLC
🇺🇸Fort Pierce, Florida, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Clinical Research Puerto Rico Inc
🇵🇷San Juan, Puerto Rico
The George Washington University Medical Center
🇺🇸Washington, District of Columbia, United States
Gary Richmond, MD, PA, Inc.
🇺🇸Fort Lauderdale, Florida, United States
Peter J Ruane MD Inc
🇺🇸Los Angeles, California, United States
The CORE Foundation
🇺🇸Chicago, Illinois, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Clinical Alliance for Research & Education
🇺🇸Annandale, Virginia, United States
Gordon E. Crofoot MD PA
🇺🇸Houston, Texas, United States
Therapeutics Concepts, PA
🇺🇸Houston, Texas, United States
Community Health Care
🇺🇸Tacoma, Washington, United States
University of California San Diego
🇺🇸San Diego, California, United States
Kaiser Permanente
🇺🇸San Francisco, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Southern Cal
🇺🇸Spokane, Washington, United States
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
Community AIDS Network
🇺🇸Clearwater, Florida, United States
Triple O Research Institute PA
🇺🇸West Palm Beach, Florida, United States
Rowan Tree Medical PA
🇺🇸Wilton Manors, Florida, United States
Duke University
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Philadelphia FIGHT
🇺🇸Philadelphia, Pennsylvania, United States
Lehigh Valley Health Network, Network Office of Research and Innovation
🇺🇸Allentown, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of California Davis
🇺🇸Sacramento, California, United States
Kansas City Free Health Clinic
🇺🇸Kansas City, Missouri, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
St. Josephs Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
AIDS Healthcare Foundation
🇺🇸Miami, Florida, United States