Conference Coverage

Are higher rifampin doses for pulmonary TB more effective?


Key clinical point: Higher rifampin doses than customarily used offer better control of TB with safety, investigators say.

Major finding: In a per-protocol analysis, reduction in TB colony-forming units was significantly faster with 15- or 20-mg/kg rifampin dose vs. the standard 10-mg/kg dose.

Data source: Randomized, controlled trial in 180 Peruvian patients with pulmonary tuberculosis.

Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases. Dr. Velásquez and Dr. Benson reported no relevant conflicts of interest.

Source: Velásquez GE et al. CROI 2018, Abstract 39LB.



– Current daily doses of rifampin for treating pulmonary tuberculosis may be too low and could be safely increased, results of a randomized phase 2 study suggest.

“Back in the 1970s, rifampin was an expensive drug, and attempts to shorten TB therapy using higher but intermittent doses of rifampin were unsuccessful at that time because of increased toxicity. That line of inquiry was essentially dormant for 40 years,” said Gustavo Velásquez, MD, from Brigham & Women’s Hospital in Boston.

Dr. Gustavo Velásquez of Brigham & Women's Hospital, Boston Neil Osterweil/MDedge News

Dr. Gustavo Velásquez

More recent controlled trials have evaluated higher daily doses of rifampin, but none thus far have looked at concentration-dependent drug activity in Latin American patients or at efficacy as a function of the parameter that is thought to best predict rifampin activity, which is the ratio of the area under the curve to the maximum inhibitory concentration (AUC/MIC) of rifampin, he said at the Conference on Retroviruses and Opportunistic Infections.

To get a better idea of optimal rifampin dosing for the treatment of pulmonary TB, Dr. Velásquez and his colleagues conducted the HIRIF (High-Dose Rifampin in Patients With TB) trial. The phase 2 study was designed to evaluate the pharmacokinetics, efficacy, and safety of higher daily rifampin doses for pulmonary TB.

They looked at the three parameters across three treatments arms: 10 mg/kg rifampin (the current standard of care), 15 mg/kg, or 20 mg/kg.

Patients in Peru were screened, enrolled, and randomized in cohorts of 60 patients each to one of the three specified dose levels, which they received either as additional rifampin tablets or placebo for the first 8 weeks of treatment, after which all patients were continued on rifampin 10 mg/kg to complete a 6-month regimen. All patients were followed for an additional 6 months to for assessment of TB recurrence.

Rifampin total doses ranged from as low as 300 mg for patients in the 30 kg-37 kg weight range, to as high as 1,500 mg for those weighing more than 70 kg.


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