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dc.contributor.authorAtwine, D
dc.contributor.authorBaudin, E
dc.contributor.authorGelé, T
dc.contributor.authorMuyindike, W
dc.contributor.authorMworozi, K
dc.contributor.authorKyohairwe, R
dc.contributor.authorKananura, K
dc.contributor.authorOrikiriza, P
dc.contributor.authorNyehangane, D
dc.contributor.authorNanjebe, DKT
dc.contributor.authorFurlan, V
dc.contributor.authorVerstuyft, C
dc.contributor.authorBarrail-Tran, A
dc.contributor.authorTaburet, A
dc.contributor.authorBonnet, M
dc.date.accessioned2020-07-11T23:04:54Z
dc.date.available2020-07-11T23:04:54Z
dc.date.issued2020-01-30
dc.date.submitted2020-07-05
dc.identifier.pmid31999314
dc.identifier.doi10.1093/jac/dkz557
dc.identifier.urihttp://hdl.handle.net/10144/619677
dc.descriptionWe regret that this article is behind a paywall.en_US
dc.description.abstractBackground: 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.en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.titleEffect of high-dose rifampicin on efavirenz pharmacokinetics: drug-drug interaction randomized trialen_US
dc.typeArticle
dc.identifier.eissn1460-2091
dc.identifier.journalThe Journal of Antimicrobial Chemotherapyen_US
dc.source.journaltitleThe Journal of antimicrobial chemotherapy
dc.source.volume75
dc.source.issue5
dc.source.beginpage1250
dc.source.endpage1258
dc.source.countryEngland


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