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Phase 3 Completed N=1,443 Randomized Treatment

Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Fixed Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Positive Participants

Source: ClinicalTrials.gov NCT01815736 ↗
Enrolled (actual)
1,443
Serious AEs
6.0%
Results posted
Apr 2016
Primary outcomePrimary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 — 95.6; 92.9; 97.2; 93.1 percentage of participants — p=0.051
◆ Published Evidence
Highly cited
304citations · ~30 / year
Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study.
The Lancet. Infectious diseases · 2016 · High-confidence link

Summary

The primary objective of this study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-containing fixed dose combination (FDC) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically suppressed HIV-infected participants as determined by having HIV-1 RNA < 50 copies/mL at Week 48.

Linked Publications (5)

  • Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study.
    The Lancet. Infectious diseases · 2016 · 304 citations · High-confidence link
  • Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials.
    AIDS (London, England) · 2019 · 160 citations · Open access · High-confidence link
  • Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.
    The lancet. HIV · 2017 · 76 citations · High-confidence link
  • Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate.
    PloS one · 2019 · 25 citations · Open access · High-confidence link
  • Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials.
    HIV research & clinical practice · 2019 · 10 citations · Open access · High-confidence link

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
95.6; 92.9; 97.2; 93.1 0.051
SECONDARY
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
1.949; -0.136; 1.468; -0.340 <0.001 sig
SECONDARY
Percent Change From Baseline in Spine BMD at Week 48
1.861; -0.110; 1.557; -0.443 <0.001 sig
SECONDARY
Change From Baseline in Serum Creatinine at Week 48
-0.01; 0.04; 0.00; 0.03 <0.001 sig
SECONDARY
Change From Baseline in the Overall EFV-related Symptom Assessment Score at Week 48
-1.6; -0.1; -1.5; -0.1 <0.001 sig
SECONDARY
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
92.8; 89.1 0.017 sig
SECONDARY
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48
92.2; 90.4; 93.5; 90.4 0.29
SECONDARY
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96
90.6; 85.3 0.003 sig
SECONDARY
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48
712; 690; 33; 27; 701; 689 0.56
SECONDARY
Change From Baseline in CD4 Cell Count at Weeks 96
701; 689; 60; 42 0.074

Eligibility Criteria

Key Inclusion Criteria

  • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
  • Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
  • Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA < 50 copies/mL at the screening visit
  • Normal echocardiograph (ECG)
  • Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
  • Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of the normal range (ULN)
  • Direct bilirubin ≤ 1.5 x ULN
  • Adequate hematologic function
  • Serum amylase ≤ 5 × ULN
  • Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
  • Female participants 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
  • Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range

Key Exclusion Criteria

  • A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
  • Hepatitis B surface antigen position
  • Hepatitis C antibody positive
  • Participants experiencing decompensated cirrhosis
  • Females who are breastfeeding
  • Positive serum pregnancy test
  • Have an implanted defibrillator or pacemaker
  • Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
  • History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
  • Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
  • Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
  • Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01815736) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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