While multidrug-resistant TB attracts much international attention, most new infections are drug-susceptible but still pose a therapeutic headache. Standard treatment regimens require daily treatment for six months, leading to high levels of non-compliance, driving the development of drug resistance. Shorter and more convenient treatments are urgently needed.
With few new TB drugs available, there is a drive to make best possible use of existing chemotherapeutics. Dr Jindani and colleagues have evaluated regimens including high doses of rifampicin and its chemical relatives, in trials run under the INTERTB umbrella.
The landmark phase III RIFAQUIN trial found that shortened treatment regimens incorporating high dose rifapentine were not as effective as standard treatments. However, a weekly dose of rifapentine was as effective as daily treatment during the last four months of therapy – offering the possibility of significantly simplified treatment regimens.
The more recent phase II RIFATOX study showed that higher doses of rifampicin did not increase the risk of liver damage. This finding, plus encouraging results in novel animal models , led to the launch of the £2.2m MRC-funded phase III RIFASHORT trial, evaluating shorter (four-month) regimens using high-dose rifampicin in Botswana, Uganda, Peru and potentially other sites in Central America and Asia.
Jindani A et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371(17):1599–608.
Jindani A et al. A randomised phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis. Int J Tuberc Lung Dis. 2016;20(6):832–8.