| Author | Kendall, Michelle A. | |
| Author | Lalloo, Umesh | |
| Author | Fletcher, Courtney V. | |
| Author | Wu, Xingye | |
| Author | Podany, Anthony T. | |
| Author | Cardoso, Sandra W. | |
| Author | Ive, Prudence | |
| Author | Benson, Constance A. | |
| Access date | 2022-07-29T16:49:42Z | |
| Available date | 2022-07-29T16:49:42Z | |
| Document date | 2021 | |
| Citation | KENDALL, Michelle A. et al. Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection. Clinical infectious diseases, v. 73, n. 4, p. 706-715, 2021 | pt_BR |
| ISSN | 1058-4838 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/54079 | |
| Language | eng | pt_BR |
| Publisher | Oxford | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection | pt_BR |
| Type | Article | |
| DOI | 10.1093/cid/ciab097 | |
| Abstract | 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 <250 ng/mL. Proportions with week 48 HIV-1 RNA <400 copies/mL were 58%, 67%, and 61%, respectively, in arms A, B, and C.
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. | pt_BR |
| Affilliation | Harvard T.H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA. | pt_BR |
| Affilliation | Enhancing Care Foundation. Durban International Clinical Research Site. Durban, South Africa. | pt_BR |
| Affilliation | University of Nebraska Medical Center. UNMC Center for Drug Discovery. Omaha, Nebraska, USA. | pt_BR |
| Affilliation | Harvard T.H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA. | pt_BR |
| Affilliation | University of Nebraska Medical Center. UNMC Center for Drug Discovery. Omaha, Nebraska, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | University of the Witwatersrand. Faculty of Health Sciences. School of Clinical Medicine. Department of Internal Medicine. Clinical HIV Research Unit. Johannesburg, South Africa. | pt_BR |
| Affilliation | University of California. Antiviral Research Center. San Diego, California, USA. | pt_BR |
| Subject | HIV | pt_BR |
| Subject | Lopinavir | pt_BR |
| Subject | Rifabutin | pt_BR |
| Subject | Rifampin | pt_BR |
| Subject | Tuberculosis | pt_BR |
