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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV-1-infection, Antiretroviral Therapy

Intervention / Treatment
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* Drug: Continuation of boosted PI
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to the B/F/TAF or continuation bPI group in a 1:1 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Boosted PI Group<br>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<br>* 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<br>|
| Experimental: B/F/TAF Group<br>Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily. | Drug: B/F/TAF<br>* Single-tablet, fixed dose combination of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Second-line therapy, Integrase strand transfer inhibitor, Protease inhibitor