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    Jan 17, 2021
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    Effect of high-dose rifampicin on efavirenz pharmacokinetics: drug-drug interaction randomized trial

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    Authors
    Atwine, D
    Baudin, E
    Gelé, T
    Muyindike, W
    Mworozi, K
    Kyohairwe, R
    Kananura, K
    Orikiriza, P
    Nyehangane, D
    Nanjebe, DKT
    Furlan, V
    Verstuyft, C
    Barrail-Tran, A
    Taburet, A
    Bonnet, M
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    Issue Date
    2020-01-30
    Submitted date
    2020-07-05
    
    Metadata
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    Journal
    The Journal of Antimicrobial Chemotherapy
    Abstract
    Background: High-dose rifampicin is considered to shorten anti-TB treatment duration but its effect on antiretroviral metabolism is unknown. Objectives: To assess the effect of doubling the rifampicin dose (to 20 mg/kg/day, R20) on efavirenz pharmacokinetics (PK) in HIV/TB coinfected patients. Methods: Open-label Phase 2 drug-drug interaction randomized trial. Pulmonary TB, ART-naive adults were randomized to R20 and either efavirenz 600 mg (EFV600) or 800 mg (EFV800), or rifampicin 10 mg/kg/day (R10) and EFV600 with a 1:1:1 ratio. Patients were first started on TB treatment and 2-4 weeks later started on ART. They were switched to R10 and EFV600 after 8 weeks. Full PK sampling was done 4 weeks (on rifampicin) and 24 weeks (off rifampicin) after ART initiation. Transaminases, plasma HIV-1 RNA and sputum cultures were monitored. The efavirenz geometric mean ratio (GMR) of AUC at 4 and 24 weeks after ART initiation within the same patient was calculated in each arm and its 90% CI was compared with a preset range (0.70-1.43). Results: Of 98 enrolled patients (32 in the R20EFV600 arm, 33 in the R20EFV800 arm and 33 in the R10EFV600 arm), 87 had full PK sampling. For the R20EFV600, R20EFV800 and R10EFV600 arms, GMRs of efavirenz AUC were 0.87 (90% CI: 0.75-1.00), 1.12 (90% CI: 0.96-1.30) and 0.96 (90% CI: 0.84-1.10). Twelve weeks after ART initiation, 78.6%, 77.4% and 72.4% of patients had HIV-1 RNA below 100 copies/mL and 85.7%, 86.7% and 80.0% had Week 8 culture conversion, respectively. Two patients per arm experienced a severe increase in transaminases. Conclusions: Doubling the rifampicin dose had a small effect on efavirenz concentrations and was well tolerated.
    Publisher
    Oxford University Press
    URI
    http://hdl.handle.net/10144/619677
    DOI
    10.1093/jac/dkz557
    PubMed ID
    31999314
    Type
    Article
    Language
    en
    Description
    We regret that this article is behind a paywall.
    EISSN
    1460-2091
    ae974a485f413a2113503eed53cd6c53
    10.1093/jac/dkz557
    Scopus Count
    Collections
    Pharmacy

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