KHOPOTSO: At present, many TB patients do not complete their treatment because it makes them feel sick and they need to take it for six long months. But the huge problems of drug-resistant TB and the tendency for TB and HIV to go together means there is an      

urgent need for better and more effective medicines. This is according to a paper released this week, ahead of the world’€™s largest meeting on lung diseases, the World Conference on Lung Health to be held in Cape Town, from this weekend. The paper calls for a rapid and multi-candidate clinical trials network to test new agents aimed at treating Multi-Drug Resistant Tuberculosis. Speaking via telephone, Harvard Medical School’€™s Dr Nicole Mitnick, and the lead author of the paper, explains the need for a range of trials running simultaneously.      

Dr CAROLE MITNICK: One is the growing magnitude of the problem’€¦ There’€™s also been growing evidence that these MDR strains are actually, probably equally likely to cause disease as the drug-susceptible strains, and that even just a few patients with a very infectious strain of MDR TB can have an enormous impact on the epidemiology of MDR TB, meaning that they can transmit to lots and lots of people before they either get effective treatment or more likely die.                    

KHOPOTSO: Each year, over 400 000 new cases of MDR TB are reported world-wide. The worst form of drug-resistant TB, known as Extensively Drug Resistant (XDR) TB has been identified in 37 countries. The overlap with HIV is profound, with patients dying quickly, and often without access to appropriate treatment. However, TB drugs were developed over four decades ago, and since then interest in developing new TB drugs has been virtually nil. This has left the world with very limited treatment options for MDR TB.

Dr CAROLE MITNICK: It has largely been ignored, with the exception of in extremely wealthy settings. This is really due to a perceived lack of importance of Multi-Drug Resistant Tuberculosis. And this perceived lack of importance has led to almost complete paralysis on the part of the TB research community (and) drug development firms in developing new drugs that could be used for MDR-TB and also in trying to improve regimens’€¦

KHOPOTSO: But why has this apathy in drug development for MDR TB set in?

Dr CAROLE MITNICK: The perception has been that the treatment for MDR TB is too hard and too toxic. Therefore, the alternative in resource-poor settings has been to just isolate people, hope that they don’€™t transmit to anyone else, and let them die. It’€™s been considered too expensive in these settings. Drug-Resistant TB was thought to be less transmissible than drug-susceptible TB. Therefore, it wasn’€™t likely to be a huge epidemiologic concern.

KHOPOTSO: In the paper, titled ‘€œBuilding Clinical Trials Capacity for Tuberculosis Drugs in High-Burden Countries’€, Mitnick and colleagues remind us that that isn’€™t the case.          

Dr CAROLE MITNICK: The problem is so enormous and the urgency so great that there really can be no additional delay in developing new regimens for drug-resistant disease.

KHOPOTSO: To speed up results from clinical trials, the paper calls for enrolment of fewer participants than is usually the norm. French humanitarian agency Doctors Without Borders, MSF, supports the proposal for multi-candidate TB drug trials. Dr Tido von Schon-Angerer, is the Executive Director.

Dr TIDO VON SCHON-ANGERER: What is exciting about this strategy to test new drugs in MDR (TB) is really two-fold. One, it’€™s really a way to accelerate development. We need fewer patients to show that the drugs can work. Secondly, it will allow some improvement of this desperate situation that we have for MDR (TB) treatment. At the moment the goal of drug developers in TB, and they are not many ‘€“ the activities are very limited ‘€“ is to have a completely new treatment for TB, that is, you could treat with (it), and it’€™s shorter, and it’€™s better, and you can also give it to drug-resistant TB patients as well. That is a very important and good goal, but it’€™s going to take us one or two decades to get there. What is important today is that we have the MDR (TB) situation worsening everyday and we need to make sure that any of the new drugs that come through the pipeline, we move them through as quickly as possible, and doing tests in MDR (TB) patients is one way of doing this.