1. Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349)
- Author
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Pettit, April C, Phillips, Patrick PJ, Kurbatova, Ekaterina, Vernon, Andrew, Nahid, Payam, Dawson, Rodney, Dooley, Kelly E, Sanne, Ian, Waja, Ziyaad, Mohapi, Lerato, Podany, Anthony T, Samaneka, Wadzanai, Savic, Rada M, Johnson, John L, Muzanyi, Grace, Lalloo, Umesh G, Bryant, Kia, Sizemore, Erin, Scott, Nigel, Dorman, Susan E, Chaisson, Richard E, Swindells, Susan, and team, for the Tuberculosis Trials Consortium Study 31 AIDS Clinical Trials Group A5349 study
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Lung ,Clinical Trials and Supportive Activities ,Tuberculosis ,Rare Diseases ,HIV/AIDS ,Clinical Research ,Vaccine Related ,Prevention ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Humans ,Rifampin ,Moxifloxacin ,Antitubercular Agents ,HIV ,Isoniazid ,Drug Therapy ,Combination ,Tuberculosis ,Pulmonary ,HIV Infections ,phase 3 clinical trial ,rifapentine ,moxifloxacin ,tuberculosis ,human immunodeficiency virus ,Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) A5349 study team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundTuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH).MethodsPWH and CD4+ counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz.ResultsA total of 2516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4+ count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was noninferior to control (absolute difference in unfavorable outcomes -7.4%; 95% confidence interval [CI] -20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5% [95% CI, -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%).ConclusionsIn people with HIV-associated DS-PTB with CD4+ counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the 6-month control regimen and was safe.Clinical trials registrationNCT02410772.
- Published
- 2023