Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection
Autor: | Prudence Ive, Courtney V. Fletcher, Xingye Wu, Michelle A. Kendall, Constance A. Benson, Sandra W. Cardoso, Anthony T. Podany, Umesh G. Lalloo |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Microbiology (medical) Adult Male medicine.medical_specialty Rifabutin Anti-HIV Agents 030106 microbiology Cmax Lopinavir/ritonavir HIV Infections Gastroenterology Lopinavir 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Tuberculosis 030212 general & internal medicine Ritonavir business.industry Coinfection HIV HIV Protease Inhibitors Raltegravir Major Articles and Commentaries Infectious Diseases Pharmacodynamics Drug Therapy Combination Female Rifampin business medicine.drug |
Zdroj: | Clin Infect Dis |
ISSN: | 1537-6591 |
Popis: | Background Protease inhibitor-based antiretroviral therapy may be used in resource-limited settings in persons with human immunodeficiency virus and tuberculosis (HIV-TB). Data on safety, pharmacokinetics/pharmacodynamics (PK/PD), and HIV-TB outcomes for lopinavir/ritonavir (LPV/r) used with rifampin (RIF) or rifabutin (RBT) are limited. Methods We randomized adults with HIV-TB from July 2013 to February 2016 to arm A, LPV/r 400 mg/100 mg twice daily + RBT 150 mg/day; arm B, LPV/r 800 mg/200 mg twice daily + RIF 600 mg/day; or arm C, LPV/r 400 mg/100 mg twice daily + raltegravir (RAL) 400 mg twice daily + RBT 150 mg/day. All received two nucleoside reverse transcriptase inhibitors and other TB drugs. PK visits occurred on day 12 ± 2. Within-arm HIV-TB outcomes were summarized using proportions and 95% CIs; PK were compared using Wilcoxon tests. Results Among 71 participants, 52% were women; 72% Black; 46% Hispanic; median age, 37 years; median CD4+ count, 130 cells/mm3; median HIV-1 RNA, 4.6 log10 copies/mL; 46% had confirmed TB. LPV concentrations were similar across arms. Pooled LPV AUC12 (157 203 hours × ng/mL) and Ctrough (9876 ng/mL) were similar to historical controls; RBT AUC24 (7374 hours × ng/mL) and Ctrough (208 ng/mL) were higher, although 3 participants in arm C had RBT Cmax Conclusions Double-dose LPV/r+RIF and LPV/r+RBT 150mg/day had acceptable safety, PK and TB outcomes; HIV suppression was suboptimal but unrelated to PK. Faster RBT clearance and low Cmax in 3 participants on RBT+RAL requires further study. |
Databáze: | OpenAIRE |
Externí odkaz: |