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. 2020 Jun 26;20(1):449.
doi: 10.1186/s12879-020-05169-2.

Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients

Seni Kouanda  1 , Henri Gautier Ouedraogo  2 , Kadari Cisse  2 , Tegwinde Rebeca Compaoré  2 , Giorgia Sulis  3   4 , Serge Diagbouga  2 , Alberto Roggi  5 , Grissoum Tarnagda  2 , Paola Villani  6 , Lassana Sangare  7 , Jacques Simporé  8 , Mario Regazzi  6 , Alberto Matteelli  5
Affiliations

Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients

Seni Kouanda et al. BMC Infect Dis. .

Abstract

Background: This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection.

Methods: This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay.

Results: The Cmax and AUC0-12h medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC0-12h = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC0-12h = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC0-12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit (< 300 ng/mL) in the 150 mg RBT arm, while the Cmax was above this threshold for all patients in the 300 mg RBT arm. Additionally, at 48 h after drug ingestion, all patients had a mycobacterial minimum inhibitory concentration (MIC) above the limit (> 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm.

Conclusion: This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria.

Trial registration: PACTR201310000629390, 28th October 2013.

Keywords: Burkina Faso; HIV/tuberculosis co-infection; Lopinavir; Pharmacokinetic; Rifabutin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient Flow Chart for the study
Fig. 2
Fig. 2
Median plasma RBT and d-RBT concentrations at specified times after the administration of RBT (150 mg or 300 mg EOD) combined with lopinavir/ritonavir (200 mg/50 mg)
See this image and copyright information in PMC

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