Clinical trial NCT04311957: Continuation of Protease-Inhibitor Based Second-Line Therapy vs. Switch to B/F/TAF in Virologically Suppressed Adults
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV-1-infection
Antiretroviral Therapy
Keywords: HIV
Second-line therapy
Integrase strand transfer inhibitor
Protease inhibitor
Lead sponsor: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Harvard Medical School (HMS and HSDM)
name: Analysis Group, Inc.
name: Weill Medical College of Cornell University
First posted: 2020-03-17
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to the B/F/TAF or continuation bPI group in a 1:1 ratio.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Virologic failure - 200 Copies/mL cut-off
timeFrame: Week 48
Secondary outcomes:
measure: Virologic failure - 50 Copies/mL cut-off
timeFrame: Week 48
measure: Virologic failure - 1000 Copies/mL cut-off
timeFrame: Week 48
measure: Tolerability as measured by discontinuing medication
timeFrame: Entry to 48 weeks
measure: Adverse events
timeFrame: Entry to 48 weeks
measure: Change in cholesterol
timeFrame: Entry to 48 weeks
measure: Change in weight
timeFrame: Entry to 48 weeks
measure: Change in body mass index
timeFrame: Entry to 48 weeks
measure: Weight gain of 10% or greater
timeFrame: Entry to 48 weeks
measure: Change in waist circumference
timeFrame: Entry to 48 weeks
measure: Waist to hip ratio
timeFrame: Entry to 48 weeks
measure: Adherence
timeFrame: Entry to 48 weeks
Other outcomes:
Locations:
city: Port-au-Prince
country: Haiti
facility: GHESKIO
Study officials:
affiliation: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
name: Patrice Severe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital/Harvard Medical School
name: Serena Koenig, MD
role: PRINCIPAL_INVESTIGATOR
References: