Continuation of Protease-Inhibitor Based Second-Line Therapy vs. Switch to B/F/TAF in Virologically Suppressed Adults

NCT04311957 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: CO-US-380-5733
• Study Type: interventional
• Target: 386
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized trial compares the efficacy of switching to a fixed-dose combination of B/F/TAF versus continuing a boosted protease inhibitor (bPI) regimen in HIV-1 infected participants who are virologically suppressed (HIV-1 RNA \<200 copies) on a second-line bPI regimen. Half of participants will receive B/F/TAF and half will continue a bPI regimen. The hypothesize is that B/F/TAF will have efficacy that is non-inferior to the boosted PI regimen.

Conditions

HIV-1-infection; Antiretroviral Therapy

Keywords

HIV; Second-line therapy; Integrase strand transfer inhibitor; Protease inhibitor

Outcome Measures

Primary Outcomes (1)

• Virologic failure - 200 Copies/mL cut-off

  Proportion of participants with HIV-1 RNA at least 200 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm

  Week 48

Secondary Outcomes (11)

• Virologic failure - 50 Copies/mL cut-off

  Week 48

• Virologic failure - 1000 Copies/mL cut-off

  Week 48

• Tolerability as measured by discontinuing medication

  Entry to 48 weeks

• Adverse events

  Entry to 48 weeks

• Change in cholesterol

  Entry to 48 weeks

Study Arms (2)

Boosted PI Group

ACTIVE COMPARATOR

Continuation of the same second-line regimen taken prior to entry: This includes either Lopinavir/ritonavir (LPVr) 400 mg/100 mg BID or Atazanavir/ritonavir (ATV/r) 300 mg/100 mg QD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs).

Drug: Continuation of boosted PI

B/F/TAF Group

EXPERIMENTAL

Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.

Drug: B/F/TAF

Interventions

Continuation of boosted PI DRUG

Continuation of the same second-line regimen taken prior to entry: LPVr 400 mg/100 mg BID or ATVr 300 mg/100 mg QD + 2 NRTIs

Boosted PI Group

B/F/TAF DRUG

Single-tablet, fixed dose combination of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.

B/F/TAF Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ability and willingness to give informed consent.
• Age ≥18 years
• History of meeting WHO criteria for immunologic or virologic failure after receipt of a first-line treatment regimen for ≥6 months
• Currently receiving a second-line ART regimen including either ATVr or LPVr + 2 NRTIs for ≥6 months
• At least one HIV-1 RNA \<200 copies/mL within 12 months prior to enrollment, and no HIV-1 RNA of at least 200 copies/mL during this period.
• Plasma HIV-1 RNA \<200 copies/mL at Screening Visit.
• eGFR ≥ 50 mL/min according to the MDRD study equation for creatinine clearance
• Hepatic transaminases (AST and ALT) \</=5X upper limit of normal (ULN)
• No active TB
• Women of childbearing age must agree to take reliable contraception

You may not qualify if:

• Active World Health Organization Stage 3 or 4 condition
• Treatment with an INSTI in the past
• Gap in care of at least one month in the prior six months
• Current alcohol or substance use judged by investigator to potentially interfere with participant study compliance
• History of poor adherence, that in the opinion of the investigator, would potentially interfere with study compliance
• Pregnant or breastfeeding at screening visit
• Planning to transfer care

Sponsors & Collaborators

• Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic: lead
• Brigham and Women's Hospital: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Analysis Group, Inc.: collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

GHESKIO

Port-au-Prince, Haiti

Location

Related Publications (1)

• Severe P, Pierre S, Homeus F, Marc JB, Trevisi L, Aristhomene ML, Bernadin GR, Lavoile K, Rivera V, Duchatellier CF, Joseph MJ, Wu J, Rouzier V, Preval F, Jean E, Bernadin J, Zion A, Pierre Louis Forestal G, Avila-Rios S, Garcia Morales C, Zhang A, Israelski D, Apollon A, Dumont E, Fox E, Cremieux PY, Pape JW, Collins SE, Liautaud B, Sax PE, Koenig SP. Bictegravir, emtricitabine, and tenofovir alafenamide versus ritonavir-boosted protease inhibitor-based antiretroviral therapy in people with HIV and viral suppression on second-line therapy in Haiti: an open-label, randomised, non-inferiority trial. Lancet HIV. 2025 Sep;12(9):e616-e626. doi: 10.1016/S2352-3018(25)00130-4.

  PMID: 40883049 DERIVED

Study Officials

• Patrice Severe, MD

  Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic

  PRINCIPAL INVESTIGATOR

• Serena Koenig, MD

  Brigham and Women's Hospital/Harvard Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrice Severe, MD

CONTACT

718-962-4585; patsevere@gheskio.org

Serena Koenig, MD

CONTACT

617-413-4090; skoenig@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to the B/F/TAF or continuation bPI group in a 1:1 ratio.

Study Record Dates

• First Submitted: March 15, 2020
• First Posted: March 17, 2020
• Study Start: September 1, 2020
• Primary Completion: May 31, 2022
• Study Completion: November 30, 2022
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

HA (1)