Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349)
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 76(2023), 3 vom: 08. Feb., Seite e580-e589 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pettit, April C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.02.2023 Date Revised 29.09.2023 published: Print ClinicalTrials.gov: NCT02410772 Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciac707 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349) |
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| 500 | |a Date Revised 29.09.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02410772 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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%) | ||
| 520 | |a 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 | ||
| 520 | |a CLINICAL TRIALS REGISTRATION: NCT02410772 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
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| 700 | 1 | |a Phillips, Patrick P J |e verfasserin |4 aut | |
| 700 | 1 | |a Kurbatova, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Vernon, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Nahid, Payam |e verfasserin |4 aut | |
| 700 | 1 | |a Dawson, Rodney |e verfasserin |4 aut | |
| 700 | 1 | |a Dooley, Kelly E |e verfasserin |4 aut | |
| 700 | 1 | |a Sanne, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Waja, Ziyaad |e verfasserin |4 aut | |
| 700 | 1 | |a Mohapi, Lerato |e verfasserin |4 aut | |
| 700 | 1 | |a Podany, Anthony T |e verfasserin |4 aut | |
| 700 | 1 | |a Samaneka, Wadzanai |e verfasserin |4 aut | |
| 700 | 1 | |a Savic, Rada M |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, John L |e verfasserin |4 aut | |
| 700 | 1 | |a Muzanyi, Grace |e verfasserin |4 aut | |
| 700 | 1 | |a Lalloo, Umesh G |e verfasserin |4 aut | |
| 700 | 1 | |a Bryant, Kia |e verfasserin |4 aut | |
| 700 | 1 | |a Sizemore, Erin |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Nigel |e verfasserin |4 aut | |
| 700 | 1 | |a Dorman, Susan E |e verfasserin |4 aut | |
| 700 | 1 | |a Chaisson, Richard E |e verfasserin |4 aut | |
| 700 | 1 | |a Swindells, Susan |e verfasserin |4 aut | |
| 700 | 0 | |a Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) A5349 study team |e verfasserin |4 aut | |
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