Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349). (30th August 2022)

• Record Type: Journal Article
• Authors: Pettit, April C; Phillips, Patrick P J; 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
• Is Part Of: Clinical infectious diseases. Volume 76:Number 3(2023)
• Page Start: e580
• Page End: e589
• Publication Date: 2022-08-30
• Subjects: phase 3 clinical trial -- rifapentine -- moxifloxacin -- tuberculosis -- human immunodeficiency virus; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciac707
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Tuberculosis (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). Methods: PWH 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. Results: A 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%). Conclusions: In 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 Registration: NCT02410772. Abstract : In a prespecified subgroup analysis including TBTC S31/ACTG 5349 participants with HIV-associated drug-susceptible pulmonary tuberculosis on efavirenz-based therapy, the 4-month regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol was safe and had noninferior efficacy compared to the 6-month control.