A5290 "A Randomized, Phase 2b Study of a Double-Dose Lopinavir/Ritonavir-Based Antiretroviral Regimen with Rifampin-Based Tuberculosis Treatment versus a Standard-Dose Lopinavir/Ritonavir-Based Antiretroviral Regimen with Rifabutin-Based Tuberculosis Treatment with or without Raltegravir in HIV-1-Infected Persons Requiring Treatment for Active TB and HIV"
Study Objectives:
Laymans Summary:
Abstract of Study:
DESIGN A5290 is a prospective, randomized (1:1:1), open-label, phase 2b study comparing three lopinavir/ritonavir (LPV/r)-based antiretroviral (ARV) regimens among participants in high tuberculosis (TB) endemic resource-constrained settings undergoing treatment for confirmed or probable TB and requiring protease inhibitor (PI)-based antiretroviral therapy (ART). A two accrual period design will be used, including a full pharmacokinetic (PK) and safety evaluation to be conducted when 54-60 participants enrolled during the accrual period 1 have completed 28 days of ARV treatment and day 12 ± 2 (after initiation of ART) drug levels are available (an early interim PK and safety evaluation will also be completed when 10-12 participants per arm have completed 28 days of ARV treatment and day 12 ± 2 drug levels are available).
DURATION Each participant will be followed until week 72.
SAMPLE SIZE 471 participants.
POPULATION HIV-infected persons (male or female) at least 18 years of age with documented HIV infection, a clinical diagnosis of probable or confirmed active TB (including extrapulmonary TB) with susceptibility to rifampin (RIF), and who require a PI-based ARV regimen.
REGIMENS Study-provided drugs include lopinavir/ritonavir (LPV/r), ritonavir (RTV), raltegravir (RAL), and rifabutin (RBT).
Anti-TB therapy: Isoniazid (INH) 300 mg daily, RBT 300 mg daily, then 150 mg daily upon initiation of ART, ethambutol (EMB) (weight-based dose) daily, pyrazinamide (PZA) (weight-based dose) daily, and pyridoxine 25 mg daily. EMB and PZA will be discontinued after 8 weeks of treatment (after completion of the intensive TB treatment phase); INH, RBT 150 mg daily (or the adjusted dose determined by PK testing), and pyridoxine will continue through week 24 for a minimum total duration of 24 weeks, and may continue beyond 24 weeks to a maximum of 48 weeks at the discretion of the primary clinician; the protocol core team must be notified (actg.corea5290@fstrf.org) if TB treatment is continued beyond 24 weeks.
After completion of TB treatment, LPV/r + two NRTIs will be continued with LPV/r at standard dosing (400mg/100mg BID) through week 72.
Arm B
ART: LPV 800 mg/RTV 200 mg BID + two NRTIs.
Anti-TB therapy: INH 300 mg daily, rifampin (RIF) (weight-based dose) daily, EMB (weight-based dose) daily, PZA (weight-based dose) daily, and pyridoxine 25 mg daily. EMB and PZA will be discontinued after 8 weeks of treatment (after completion of the intensive TB treatment phase); INH, RIF, and pyridoxine will continue through week 24 for a minimum total duration of 24 weeks, and may be continued beyond 24 weeks to a maximum of 48 weeks at the discretion of the primary clinician; the protocol core team must be notified (actg.corea5290@fstrf.org) if TB treatment is continued beyond 24 weeks.
After completion of TB treatment, LPV/r + two NRTIs will be continued with LPV/r at standard dosing (400mg/100mg BID) through week 72.
Anti-TB therapy: INH 300 mg daily, RBT 300 mg daily, then 150 mg daily upon initiation of ART, EMB (weight-based dose) daily, PZA (weight-based dose) daily, and pyridoxine 25 mg daily. EMB and PZA will be discontinued after 8 weeks of treatment (after completion of the intensive TB treatment phase); INH, RBT 150 mg daily (or the adjusted dose determined by PK), and pyridoxine will be continued through week 24 for a minimum total duration of 24 weeks, and may be continued beyond 24 weeks to a maximum of 48 weeks at the discretion of the primary clinician; the protocol core team must be notified (actg.corea5290@fstrf.org) if TB treatment is continued beyond 24 weeks.
After completion of TB treatment, LPV/r + two NRTIs + RAL will be continued with LPV/r at standard dosing (400mg/100mg) through week 72.
If LPV/r is prematurely discontinued at any time during TB treatment for Arms A and C, the team must be notified, and the RBT dose should be increased to 300 mg daily pending further instructions from the team.
