Abstract
Background
Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 non-inferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had non-inferior 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 pre-specified subgroup of people with 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 post-randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% non-inferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV-status. PWH were e nrolled in a staged fashion, to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz.
Results
2,516 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 non-inferior to control (absolute difference in unfavorable outcomes -7.4% [95% CI –20.8% to +6.0%]); the rifapentine regimen was not non-inferior 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 non-inferior to the 6-month control regimen and was safe.
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