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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04311957
• Other study ID #: CO-US-380-5733
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 1, 2020
• Est. completion date: November 30, 2022

Study information

• Verified date: July 2020
• Source: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
• Contact: Patrice Severe, MD
• Phone: 718-962-4585
• Email: patsevere[@]gheskio.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 386
• Est. completion date: November 30, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antiretroviral Therapy
• HIV-1-infection

Intervention

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
• 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.

Locations

Country	Name	City	State
Haiti	GHESKIO	Port-au-Prince

Sponsors (5)

Lead Sponsor	Collaborator
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic	Analysis Group, Inc., Brigham and Women's Hospital, Harvard Medical School, Weill Medical College of Cornell University

Country where clinical trial is conducted

Haiti, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Tolerability as measured by discontinuing medication	Proportion of participants discontinuing therapy for drug-related adverse events	Entry to 48 weeks
Secondary	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
Secondary	Change in cholesterol	Median change in cholesterol	Entry to 48 weeks
Secondary	Change in weight	Median change in weight in kilograms	Entry to 48 weeks
Secondary	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
Secondary	Weight gain of 10% or greater	Proportion of participants with weight gain of at least 10% (in kilograms)	Entry to 48 weeks
Secondary	Change in waist circumference	Median change in waist circumference	Entry to 48 weeks
Secondary	Waist to hip ratio	Median change in waist to hip ratio	Entry to 48 weeks
Secondary	Adherence	Median adherence as measured by pharmacy refill records	Entry to 48 weeks