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

Phase 4

• Conditions: HIV-1-infection; Antiretroviral Therapy
• Interventions: Drug: Continuation of boosted PI; Drug: B/F/TAF

• Registration Number: NCT04311957
• Lead Sponsor: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic

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.

Study Timeline

• Study First Submitted: 2020-03-15
• Study First Submitted QC: 2020-03-15
• Study First Posted: 2020-03-17
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-30
• Last Update Posted: 2020-08-03
• Study Start: 2020-09-01
• Primary Completion: 2022-05-31
• Study Completion: 2022-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 386

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Boosted PI Group	Continuation of boosted PI	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).
B/F/TAF Group	B/F/TAF	Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.

Primary Outcome Measures

Name	Time	Method
Virologic failure - 200 Copies/mL cut-off	Week 48	Proportion of participants with HIV-1 RNA at least 200 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm

Secondary Outcome Measures

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

Trial Locations

Locations (1)

GHESKIO; 🇭🇹 Port-au-Prince, Haiti