Conference on Retroviruses and Opportunistic Infections (CROI)

Conference on Retroviruses and Opportunistic Infections (CROI)

February 25, 2015
2 min read

High-dose rifampin reduced time to TB culture conversion

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SEATTLE — A treatment regimen including a high dose of rifampin could reduce treatment duration for patients with tuberculosis, according to data presented at CROI 2015.

Martin J. Boeree, MD, PhD, of Radboud University Medical Center in Nijmegan, Netherlands, and colleagues conducted a multi-arm, multi-stage (MAMS) study examining the length and efficacy of various TB treatments in 365 adult TB patients from South Africa and Tanzania, of which 7% were co-infected with HIV.

“Shorter regimens are urgently needed for the treatment of TB,” the researchers wrote. “Adaptive designs such as MAMS are feasible for multi-center TB clinical trials and could speed regimen development.”

The patients were randomly assigned 1:1:1:1:2 to one of five experimental treatment arms: 12 weeks of SQ109 with standard dose rifampin, isoniazid and pyrazinamide; 12 weeks of SQ109 and 20mg/kg rifampin with pyrazinamide and isoniazid; 12 weeks of moxifloxacin and 20mg/kg rifampin with pyrazinamide and isoniazid; 12 weeks of 35mg/kg rifampin with ethambutol, pyrazinamide and isoniazid; and a control arm consisting of 8 weeks of rifampin, isoniazid, pyrazinamide and ethambutol. These treatments were then followed by 26 weeks of standard rifampin and isoniazid.

Martin J. Boeree

After the interim analysis, recruitment to both arms including SQ109 was halted. There was no reduction in time to culture conversion. The high-dose rifampin arm saw the greatest reduction in time to culture conversion, with a covariate-adjusted HR of 1.75 (95% CI, 1.21-2.55) compared to control over 12 weeks. When compared to previous TB trials, the covariate-adjusted HR over 8 weeks was 1.99 (95% CI, 1.21-3.29). A modest reduction was observed in the 20mg/kg rifampin arm, resulting in a 12 week HR of 1.42 (95% CI, 0.98-2.05) and an 8 week HR of 1.69 (95% CI, 1.02-2.80), when compared to previous TB trials.

“Thirty-five mg/kg of rifampin resulted in an increased likelihood of, and shorter time to, culture conversion on liquid media,” Boeree said during an oral presentation. “All arms appear to be safe and well-tolerated, and we can say our multi-arm, multi-stage design was successfully implemented in multicenter TB trial in Africa.” – by Dave Muoio


Boeree, et al. Abstract # 95LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.

Disclosure: The researchers report no relevant financial disclosures.