Dose Escalation Study to Determine the Pharmacokinetics of Atazanavir Administered With RIfampicin to HIV Positive Adults on sEcond-line ART Regimen With Suppressed HIV-1 Viral Load

• Status: Recruiting
• Trial end date: 2023-08-20

Summary

The standard treatment for TB consists of rifampicin (RIF) as part of the regimen. However, due to drug-drug interactions (DDI), the bioavailability of PIs is greatly reduced when co-administered with RIF necessitating use of higher doses of the PI to overcome this effect. However, the potential effect of this increased dose on the DDI with bPIs is uncertain. Though some data has been collected that shows safe use of higher doses of LPV to overcome the DDI with standard doses of RIF in HIV-infected individuals, no substantive data has been collected on ATV to correctly adjust its dose when co-administered with RIF-based TB treatment.

Physiologically-based pharmacokinetic (PBPK) modelling was developed to understand ATV and RIF DDIs, and identified potential dosing strategies to overcome this challenge in adults and special populations under workpackage 1 of the VirTUAL consortium. From this work, it is anticipated that the dose of ATV/r should be increased from 300/100 once daily to 300/100mg twice daily in order to overcome the interaction with rifampicin and attain therapeutic plasma concentrations.

This dose escalation trial aims to:

1. Evaluate the steady state plasma and intracellular PK of ATV/r, when administered in adjusted (PBPK model-predicted) doses concurrently with RIF

2. Evaluate the safety and tolerability / acceptability of the adjusted dose of ATV/r that provides the therapeutic concentration when co-administered with RIF.

3. Evaluate the concentration of dolutegravir (DTG) and RIF when co-administered and explore the potential DDI with ATV/r

• Phase: Phase 2/Phase 3

Details

• Lead Sponsor: University of Liverpool
• Collaborators: European and Developing Countries Clinical Trials Partnership (Funder); Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Joint Clinical Research Centre, Kampala, Uganda; University of Cape Town, Cape Town, South Africa; University of Turin, Turin, Italy
• Treatments: Atazanavir Sulfate; Rifampin