Pharmacokinetic Study of Two Different Rifabutin Doses Co-administered with Lopinavir/ritonavir in African HIV and Tuberculosis Co-infected Adult Patients

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2020 Jun 28

PMID 32590942

Citations 2

Authors

Seni Kouanda

Henri Gautier Ouedraogo

Kadari Cisse

Tegwinde Rebeca Compaore

Giorgia Sulis

Serge Diagbouga

Alberto Roggi

Grissoum Tarnagda

Paola Villani

Lassana Sangare

Jacques Simpore

Mario Regazzi

Alberto Matteelli

Affiliations

Soon will be listed here.

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 AUC medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC (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.

Citing Articles

Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection.

Kendall M, Lalloo U, Fletcher C, Wu X, Podany A, Cardoso S Clin Infect Dis. 2021; 73(4):706-715.

PMID: 34398956 PMC: 8366816. DOI: 10.1093/cid/ciab097.

Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials.

Shu Y, Deng Z, Wang H, Chen Y, Yuan L, Deng Y AIDS Res Ther. 2021; 18(1):25.

PMID: 33933131 PMC: 8088572. DOI: 10.1186/s12981-021-00348-w.

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