NCT02603107

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

Completed Phase 3 Results posted Last updated 29 December 2020

What this trial tests

Phase 3 trial testing RTV in HIV-1 Infection in 578 participants. Completed in 23 December 2019.

Timeline

20 November 2015

Primary endpoint
15 May 2017

23 December 2019

Quick facts

Lead sponsor	Gilead Sciences
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	578
Start date	20 November 2015
Primary completion	15 May 2017
Estimated completion	23 December 2019
Sites	119 locations across France, Italy, Dominican Republic, Belgium, United Kingdom, Germany, Canada, Puerto Rico

Drugs / interventions tested

• RTV
• ATV — full drug profile →
• DRV — full drug profile →
• COBI
• ATV/co — full drug profile →
• DRV/co — full drug profile →
• FTC/TDF
• ABC/3TC — full drug profile →
• B/F/TAF

Conditions studied

• HIV-1 Infection — all drugs for HIV-1 Infection →

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm Primary · Week 48

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 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.

Group	Value	95% CI
B/F/TAF	1.7
Stay on Baseline Regimen (SBR)	1.7

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm Secondary · Week 48

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 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.

Group	Value	95% CI
B/F/TAF	92.1
Stay on Baseline Regimen (SBR)	88.9

Change From Baseline in CD4 Cell Count at Week 48 Secondary · Baseline to Week 48

Group	Value	95% CI
B/F/TAF	25	± 151.2
Stay on Baseline Regimen (SBR)	0	± 159.4

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose date up to last dose date (maximum: 181 weeks) plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

B/F/TAF (Randomized Phase)

Serious: 17/290 (6%)

Deaths: 1/290

Stay on Baseline Regimen (SBR) (Randomized Phase)

Serious: 21/287 (7%)

Deaths: 1/287

Extension B/F/TAF From B/F/TAF

Serious: 20/272 (7%)

Deaths: 0/272

Extension B/F/TAF From SBR

Serious: 29/244 (12%)

Deaths: 1/244

Serious adverse events (91 terms)

Reaction	System	B/F/TAF (Randomized Phase)	Stay on Baseline Regimen (…	Extension B/F/TAF From B/F…	Extension B/F/TAF From SBR
Hepatitis A	Infections and infestations	—	—	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—	—
Lymphadenitis	Blood and lymphatic system disorders	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—
Coronary artery stenosis	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—
Myxomatous mitral valve degeneration	Cardiac disorders	—	—	—	—
Sinus node dysfunction	Cardiac disorders	—	—	—	—
Optic disc disorder	Eye disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Anal fistula	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Diverticular perforation	Gastrointestinal disorders	—	—	—	—
Enterocutaneous fistula	Gastrointestinal disorders	—	—	—	—
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Biliary dyskinesia	Hepatobiliary disorders	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—
Abscess limb	Infections and infestations	—	—	—	—
Acute hepatitis C	Infections and infestations	—	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	B/F/TAF (Randomized Phase)	Stay on Baseline Regimen (…	Extension B/F/TAF From B/F…	Extension B/F/TAF From SBR
Nasopharyngitis	Infections and infestations	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Syphilis	Infections and infestations	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Hepatitis A, Abortion spontaneous, Lymphadenitis, Acute myocardial infarction, Atrial fibrillation, Bradycardia, Coronary artery stenosis, Myocardial infarction.

Data from ClinicalTrials.gov NCT02603107 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Approved Antiviral Drugs over the Past 50 Years.
   De Clercq E, Li G. · · 2016 · cited 891× · PMID 27281742 · DOI 10.1128/cmr.00102-15
2. Innovation and trends in the development and approval of antiviral medicines: 1987-2017 and beyond.
   Chaudhuri S, Symons JA, Deval J. · · 2018 · cited 136× · PMID 29758235 · DOI 10.1016/j.antiviral.2018.05.005
3. 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 tr
   Daar ES, DeJesus E, Ruane P, Crofoot G, et al · · 2018 · cited 125× · PMID 29925490 · DOI 10.1016/s2352-3018(18)30091-2
4. Approved HIV reverse transcriptase inhibitors in the past decade.
   Li G, Wang Y, De Clercq E. · · 2022 · cited 71× · PMID 35847492 · DOI 10.1016/j.apsb.2021.11.009
5. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
   Andreatta K, Willkom M, Martin R, Chang S, et al · · 2019 · cited 49× · PMID 31430369 · DOI 10.1093/jac/dkz347
6. High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I.
   Sax PE, Andreatta K, Molina JM, Daar ES, et al · · 2022 · cited 23× · PMID 35466963 · DOI 10.1097/qad.0000000000003244
7. Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.
   D'Antoni ML, Andreatta K, Acosta R, Martin H, et al · · 2022 · cited 8× · PMID 34897227 · DOI 10.1097/qai.0000000000002888
8. New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs.
   Marra M, Catalano A, Sinicropi MS, Ceramella J, et al · · 2024 · cited 7× · PMID 39339960 · DOI 10.3390/v16091484