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

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

Status and phase: Unknown; Phase 4

Conditions: HIV-1-infection; Antiretroviral Therapy

Treatments: Drug: Continuation of boosted PI; Drug: B/F/TAF

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04311957

CO-US-380-5733

Details and patient eligibility

About

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.

Full 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.

Enrollment: 386 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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386 participants in 2 patient groups

Boosted PI Group

Active Comparator group

Description:

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).

Treatment:

Drug: Continuation of boosted PI

B/F/TAF Group

Experimental group

Description:

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

Treatment:

Drug: B/F/TAF