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

A Randomized Non-Inferiority Trial to Compare the Efficacy of Switching From Protease-Inhibitor Based Second-Line Therapy to Bictegravir-Tenofovir Alafenamide-Emtricitabine in Virologically Suppressed Adults in Haiti

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.

Study Overview

• Status: Unknown
• Conditions: Antiretroviral Therapy; HIV-1-infection
• Intervention / Treatment: Drug: Continuation of boosted PI; Drug: B/F/TAF

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.

• Study Type: Interventional
• Enrollment (Anticipated): 386
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Patrice Severe, MD; Phone Number: 718-962-4585; Email: patsevere@gheskio.org
• Study Contact Backup: Name: Serena Koenig, MD; Phone Number: 617-413-4090; Email: skoenig@bwh.harvard.edu

Study Locations

• Haiti
  • Port-au-Prince, Haiti
    • GHESKIO
    • Principal Investigator: Patrice Severe, MD
    • Contact: Patrice Severe, MD; Phone Number: 3448-5963; Email: patsevere@gheskio.org
    • Contact: Samuel Pierre, MD; Phone Number: 3740-7711; Email: spierre@gheskio.org
    • Sub-Investigator: Samuel Pierre, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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).	Drug: 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
Experimental: B/F/TAF Group; Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic failure - 50 Copies/mL cut-off	Proportion of participants with HIV-1 RNA at least 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm	Week 48
Virologic failure - 1000 Copies/mL cut-off	Proportion of participants with HIV-1 RNA at least 1000 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm	Week 48
Tolerability as measured by discontinuing medication	Proportion of participants discontinuing therapy for drug-related adverse events	Entry to 48 weeks
Adverse events	Proportion of participants with 1 or more NIH Division of AIDS Grade 3 or 4 adverse events (at least 1 grade increase from baseline)	Entry to 48 weeks
Change in cholesterol	Median change in cholesterol	Entry to 48 weeks
Change in weight	Median change in weight in kilograms	Entry to 48 weeks
Change in body mass index	Median change in body mass index (weight in kilograms divided by the square of height in meters)	Entry to 48 weeks
Weight gain of 10% or greater	Proportion of participants with weight gain of at least 10% (in kilograms)	Entry to 48 weeks
Change in waist circumference	Median change in waist circumference	Entry to 48 weeks
Waist to hip ratio	Median change in waist to hip ratio	Entry to 48 weeks
Adherence	Median adherence as measured by pharmacy refill records	Entry to 48 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): May 31, 2022
• Study Completion (Anticipated): November 30, 2022

Study Registration Dates

• First Submitted: March 15, 2020
• First Submitted That Met QC Criteria: March 15, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Protease inhibitor; Second-line therapy; Integrase strand transfer inhibitor
• Other Study ID Numbers: CO-US-380-5733

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes