No implication of HIV coinfection on the plasma exposure to rifampicin, pyrazinamide, and ethambutol in tuberculosis patients

Author(s)

Nardotto, Glauco Henrique Balthazar ^[1] ; Bollela, Valdes Roberto ^[2] ; Rocha, Adriana ^[1] ; Della Pasqua, Oscar ^[3] ; Lanchote, Vera Lucia ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil

^[3] UCL, Sch Pharm, Clin Pharmacol & Therapeut Grp, London - England

• Document type: Journal article
• Source: CTS-CLINICAL AND TRANSLATIONAL SCIENCE; OCT 2021.
• Web of Science Citations: 0

Abstract

There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first-line anti-tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB-HIV- group; n = 15) and HIV positive (TB-HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB-HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB-HIV+ patients, dose-normalized plasma exposure area under the curve from zero to 24 h (nAUC(0-24); geometric mean and 95% confidence interval {[}CI]) values at steady-state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74-24.59), 238.21 (95% CI 191.09-296.95), and 18.33 (95% CI 14.56-23.09) mu g center dot h/ml, respectively. Similar plasma exposure was found in the TB-HIV- patients. The geometric mean and 90% CI of the ratios between TB-HIV- and TB-HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs. (AU)

• FAPESP's process: 18/05616-3 - Clinical pharmacokinetics in infectious diseases
• Grantee: Vera Lúcia Lanchote
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/05624-0 - Pharmacokinetic-pharmacodynamic models (PK-PD) in macrophages and tuberculosis patients with application in personalized dose of rifampicin, isoniazid, pyrazinamide and ethambutol
• Grantee: Glauco Henrique Balthazar Nardotto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral