The trial's principal investigator
The new drug combination, known as PaMZ, was found to be effective in killing 99% of patients' tuberculosis bacteria within two weeks and raised the possibility that there may be a way to stem the growing tide of drug-resistant TB.
The results were presented on Monday at the International Aids Conference in Washington DC and have been published in the respected Lancet medical journal.
But the trial's principal investigator, Stellenbosch University's Dr Andreas Diacon, said he was cautiously optimistic about the results.
"We only tested the drug for two weeks and that is not really long enough for any TB treatment to work," he said.
The trial involved 85 patients, 10 of whom were placed on the standard drug regimen for TB. The other 75 patients received different combinations of TB drugs. Fifteen of them were on the PaMZ combination, which includes the novel TB drug candidate PA-824, moxyfloxacin – an established antibiotic not usually used in first-liner TB treatment – and the existing TB drug pyrazinamide.
'Very promising'
Diacon said that while the result was "very promising" it still had to be verified through long trials. This would enable the researchers to find out whether the drug is effective over the long term and rule out the possibility that patients might have a relapse.
A follow-up trial, involving 230 patients who will take the drug for a period of eight weeks, is already underway. If it is successful, the drug will move into a longer, third phase trial involving thousands of participants on three continents.
Diacon said the new approach of testing new drugs in combination with others – rather than in isolation – could make it possible produce a new drug regimen within a few years.
"From a doctor's perspective, that's amazing progress. Before, I was anticipating it could take decades for a new TB drug regimen but now it looks like it will take years," he said.
Developing countries in particular are desperately in need of new treatments for TB. Multidrug-resistant TB – TB that is resistant to the two most effective TB drugs, isoniazid and rifampicin – is on the rise. In 2010, there were 7 386 recorded cases in South Africa.
Cost-effective
MDR TB is difficult to treat, requiring patients to use second or third-line drugs and to stay on treatment for 18 to 24 months. This drives the cost of treatment up from a few hundred rand a year to thousands.
But if the PaMZ combination proves successful, it could allow doctors to treat patients with ordinary and drug-resistant TB using the same treatment regime and over the same, relatively short time period of just six months. This could increase patients' adherence to their treatment regime and at the same time lower the cost of treating TB patients.
"If this regimen works, it would be quite a cheap one," said Diacon.
Christo van Niekerk, senior director of clinical development in the Pretoria office of the non-profit TB Alliance, said early projections on the cost of such a combination drug were promising.
"It could be 90% cheaper than existing MDR treatments," he said. "For South Africa, with our burden of multidrug resistant TB patients, it will have substantial and significant implications."
Dr Rod Dawson, head of the Centre for TB Research Innovation at the UCT Lung Institute, said the other advantage of the drug was that it did not appear to interfere with the antiretrovirals used to treat HIV. The standard TB treatment regime includes the drug rifampicin, which interacts poorly with ARVs and reduces their efficiency.
One-size fits all
Because of this, doctors have to put HIV positive patients who have TB on specialised combinations of drugs. This is particularly pertinent in South Africa, where the rate of HIV and TB co-infection is high.
"With that comes added complications and cost," said Dawson. "What we really want is a one-size fits all combination, so you can add TB treatment without it having an impact on your viral suppression."
Already, questions have been raised about the possibility that TB-causing bacteria will develop resistance to even new drugs once they come to market.
But Dawson said the medical profession was become more sensitized to questions of resistance.
"We don't now we won't develop resistance from these drugs but what we do know is the lessons of the past," he said.
"We have to have careful stewardship for how these drugs are combined, how patients take the drugs and how we manage the national programs for prescribing the drugs."