Pettit A, et al. Abstract 130. Presented at: Conference on Retroviruses and Opportunistic Infections; March 6-10, 2021 (virtual meeting).
4-month TB regimen noninferior to 6-month regimen in people with HIV
A 4-month daily regimen of rifapentine and moxifloxacin was noninferior to the standard 6-month regimen for tuberculosis treatment among people with HIV enrolled in a phase 3 clinical trial, researchers reported at CROI.
“Current international guidelines recommend 6 months of treatment for drug-susceptible pulmonary TB with isoniazid, rifampicin, pyrazinamide and ethambutol,” April Pettit, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center, told Healio. “Shorter treatment regimens would facilitate improved treatment adherence and potentially reduce adverse drug-related events and treatment costs. Rifapentine (RPT) and moxifloxacin (MOX) have shown promise for TB treatment shortening in murine models.”
Through the TB Trials Consortium Study 31 an international, randomized, open-label, phase 3 noninferiority trial Pettit and colleagues compared patients receiving one of two 4-month RPT-based regimens or the 6-month control regimen. According to the study, one 4-month regimen replaced rifampin with RPT 1,200 mg (RPT regimen) and the other replaced both rifampin with RPT 1,200 mg and ethambutol with MOX 400 mg (RPT-MOX regimen). Additionally, participants with HIV on efavirenz (EFV)-based ART were enrolled in a staged fashion to allow studies of drug-drug interactions between RPT and EFV.
Pettit and colleagues enrolled 2,516 participants from 13 countries in sub-Saharan Africa and Asia, as well as from the Americas. Of these participants, 214 (8%) had HIV and all were on EFV-based ART at baseline or started within 8 weeks of enrollment.
The study demonstrated that the overall efficacy of RPT-MOX was noninferior to control after adjustment for HIV status and cavitation in the microbiologically eligible and assessable populations (absolute difference [AD] = 1%; 95% CI, –2.6% to 4.5% and AD = 2%; 95% CI, –1.1% to 5.1%, respectively), according to the researchers. Among participants with HIV, RPT-MOX was noninferior to control in the microbiologically eligible population (AD = –7.5%; 95% CI, –20.8% to 6.1%) and assessable population (AD = –6.6%; 95% CI, –18.3% to 5%), they found.
Additionally, the researchers said they identified a favorable outcome in the assessable analysis population with HIV infection in 91% of participants in the RPT-MOX arm, 74% in the RPT arm and 85% in the control arm. Additionally, fewer severe or serious adverse events were reported among patients receiving the experimental regimens than those in the control arm.
“The rifapentine-moxifloxacin regimen represents a major milestone in the pursuit of shorter TB treatment regimens for people with HIV,” Pettit said.