Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

NCT ID: NCT02603107

Last Updated: 2020-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

578 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-20

Study Completion Date

2019-12-23

Brief Summary

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The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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B/F/TAF

Randomized Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks, without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

50/200/25 mg FDC tablet administered orally once daily without regard to food

Stay on Baseline Regimen (SBR)

Randomized Phase: Participants remained on current antiretroviral (ARV) regimen consisting of ritonavir (RTV)-boosted or cobicistat (COBI)-boosted atazanavir (ATV) or darunavir (DRV), plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.

Group Type EXPERIMENTAL

RTV

Intervention Type DRUG

100 mg capsule coadministered orally with ATV or DRV once daily with food

ATV

Intervention Type DRUG

300 mg capsule administered orally once daily with food

DRV

Intervention Type DRUG

800 mg tablet administered orally once daily with food

COBI

Intervention Type DRUG

150 mg tablet coadministered orally with ATV or DRV once daily with food

ATV/co

Intervention Type DRUG

300/150 mg FDC tablet administered orally once daily with food

DRV/co

Intervention Type DRUG

800/150 mg FDC tablet administered orally once daily with food

FTC/TDF

Intervention Type DRUG

200/300 mg FDC tablet administered orally once daily without regard to food

ABC/3TC

Intervention Type DRUG

600/300 mg tablet administered orally once daily with or without regard to food

B/F/TAF

Intervention Type DRUG

50/200/25 mg FDC tablet administered orally once daily without regard to food

Interventions

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RTV

100 mg capsule coadministered orally with ATV or DRV once daily with food

Intervention Type DRUG

ATV

300 mg capsule administered orally once daily with food

Intervention Type DRUG

DRV

800 mg tablet administered orally once daily with food

Intervention Type DRUG

COBI

150 mg tablet coadministered orally with ATV or DRV once daily with food

Intervention Type DRUG

ATV/co

300/150 mg FDC tablet administered orally once daily with food

Intervention Type DRUG

DRV/co

800/150 mg FDC tablet administered orally once daily with food

Intervention Type DRUG

FTC/TDF

200/300 mg FDC tablet administered orally once daily without regard to food

Intervention Type DRUG

ABC/3TC

600/300 mg tablet administered orally once daily with or without regard to food

Intervention Type DRUG

B/F/TAF

50/200/25 mg FDC tablet administered orally once daily without regard to food

Intervention Type DRUG

Other Intervention Names

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Tybost® GS-9350 Evotaz® Prezcobix® Truvada® Biktarvy®

Eligibility Criteria

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Inclusion Criteria

* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:

* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)

Exclusion Criteria

* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
* Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
* Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
* Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements
* Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC
* Females who are pregnant (as confirmed by positive serum pregnancy test)
* Females who are breastfeeding
* Acute hepatitis in the 30 days prior to study entry
* Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either:

* Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
* Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
* Active tuberculosis infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Phoenix, Arizona, United States

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Phoenix, Arizona, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Newport Beach, California, United States

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Oakland, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Leandro, California, United States

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Torrance, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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DeLand, Florida, United States

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Fort Lauderdale, Florida, United States

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Ft. Pierce, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Pensacola, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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West Palm Beach, Florida, United States

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Wilton Manors, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Macon, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Berkley, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Buffalo, New York, United States

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The Bronx, New York, United States

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The Bronx, New York, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Huntersville, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Columbia, South Carolina, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Longview, Texas, United States

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Annandale, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Darlinghurst, New South Wales, Australia

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Sydney, New South Wales, Australia

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Fitzroy, Victoria, Australia

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Melbourne, Victoria, Australia

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Prahran, Victoria, Australia

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Brussels, , Belgium

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Ghent, , Belgium

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Santo Domingo, , Dominican Republic

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Lyon, , France

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Nantes, , France

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Nice, , France

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Paris, , France

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Paris, , France

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Tourcoing, , France

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Tours, , France

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Düsseldorf, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Berlin, , Germany

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Bonn, , Germany

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Cologne, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Frankfurt, , Germany

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Hamburg, , Germany

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München, , Germany

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München, , Germany

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Milan, , Italy

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Milan, , Italy

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Roma, , Italy

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Ponce, , Puerto Rico

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Rio Piedras, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Birmingham, , United Kingdom

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Birmingham, , United Kingdom

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Brighton, , United Kingdom

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Edinburgh, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Australia Belgium Canada Dominican Republic France Germany Italy Puerto Rico Spain United Kingdom

References

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Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, Rockstroh JK, Molina JM, Koenig E, Liu YP, Custodio J, Andreatta K, Graham H, Cheng A, Martin H, Quirk E. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018 Jul;5(7):e347-e356. doi: 10.1016/S2352-3018(18)30091-2. Epub 2018 Jun 18.

Reference Type RESULT
PMID: 29925490 (View on PubMed)

Andreatta K, Willkom M, Martin R, Chang S, Wei L, Liu H, Liu YP, Graham H, Quirk E, Martin H, White KL. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J Antimicrob Chemother. 2019 Dec 1;74(12):3555-3564. doi: 10.1093/jac/dkz347.

Reference Type RESULT
PMID: 31430369 (View on PubMed)

Avihingsanon A, Chetchotisakd P, Kiertiburanakul S, Ratanasuwan W, Siripassorn K, Supparatpinyo K, Martin H, Wang H, Wong T, Wang HY. Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials. HIV Med. 2023 Mar;24(3):290-300. doi: 10.1111/hiv.13386. Epub 2022 Aug 17.

Reference Type DERIVED
PMID: 36912172 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Statistical Analysis Plan: Week 48

View Document

Document Type: Statistical Analysis Plan: Final

View Document

Other Identifiers

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2015-004011-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-380-1878

Identifier Type: -

Identifier Source: org_study_id