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

NCT ID: NCT04311957

Last Updated: 2020-08-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 386 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2022-11-30

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.

Detailed Description

The second generation integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) and bictegravir (BIC) are widely prescribed for the treatment of HIV, due to their favorable tolerability and toxicity profile, durable efficacy, and high barrier to resistance. However, there are limited data to guide the management of patients who are already virally suppressed on a second-line bPI regimen.

Though bPIs have a high barrier to resistance and durable virologic efficacy, they have several important drug-drug interactions, are associated with unfavorable long-term metabolic effects, and may be poorly tolerated. For these reasons, a second-generation INSTI would be preferable to a boosted PI regimen, as long INSTIs are demonstrated to have non-inferior efficacy for patients who are already suppressed on a second-line bPI regimen.

In the proposed study, the efficacy of continuing the bPI regimen will be compared to switching to B/F/TAF.

Conditions

HIV-1-infection; Antiretroviral Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Boosted PI Group

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).

Group Type: ACTIVE_COMPARATOR

Continuation of boosted PI

Intervention Type: 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

B/F/TAF Group

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

Group Type: EXPERIMENTAL

B/F/TAF

Intervention Type: DRUG

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

Interventions

Continuation of boosted PI

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

Intervention Type: DRUG

B/F/TAF

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: collaborator

Analysis Group, Inc.

INDUSTRY

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrice Severe, MD

Role: PRINCIPAL_INVESTIGATOR

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

Serena Koenig, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital/Harvard Medical School

Locations

GHESKIO

Port-au-Prince, , Haiti

Countries

Haiti

Central Contacts

Patrice Severe, MD

Role: CONTACT

patsevere@gheskio.org

718-962-4585

Serena Koenig, MD

Role: CONTACT

skoenig@bwh.harvard.edu

617-413-4090

Facility Contacts

Patrice Severe, MD

Role: primary

patsevere@gheskio.org

3448-5963

Samuel Pierre, MD

Role: backup

spierre@gheskio.org

3740-7711

References

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.

Reference Type: DERIVED

PMID: 40883049 (View on PubMed)

Other Identifiers

CO-US-380-5733

Identifier Type: -

Identifier Source: org_study_id