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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir- antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam
PLoS ONE, Volume 9, No. 1, Article e84866, Year 2014
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Description
Background: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. Methods: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. Results: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2-5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. Conclusions: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. Trial Registration: ClinicalTrials.gov NCT00651066. © 2014 Lan et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3898920/bin/pone.0084866.s001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3898920/bin/pone.0084866.s002.pdf
Authors & Co-Authors
Lan, Nguyen Thi Ngoc
Unknown Affiliation
Thu, Nguyen Thi Nguyet
Unknown Affiliation
Barrail-Tran, Aurélie
Unknown Affiliation
Duc, Nguyenhong
Unknown Affiliation
Lan, Nguyen Thi Ngoc
Unknown Affiliation
Laureillard, Didier
Unknown Affiliation
Lien, Truong Xuan
Unknown Affiliation
Borand, Laurence
Unknown Affiliation
Quillet, Catherine
Unknown Affiliation
Connolly, Catherine Anne
Unknown Affiliation
Lagarde, Dominique
Unknown Affiliation
Pym, Alexander S.
Unknown Affiliation
Lienhardt, Christian
Unknown Affiliation
Dung, Nguyen Huy
Unknown Affiliation
Taburet, Anne Marie
Unknown Affiliation
Harries, Anthony David
Unknown Affiliation
Statistics
Citations: 41
Authors: 16
Affiliations: 12
Identifiers
Doi:
10.1371/journal.pone.0084866
e-ISSN:
19326203
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Randomised Control Trial