New TB drug combination raises hopes

HIV patients have to take several drugs every day to keep the deadly virus HIV at bay. If they get co-infected with TB - which happens quite often - they need to swallow even more pills.

Problems arise if TB and HIV drugs start to interact with each other. "One drug can cause other drugs to be present in greater or lesser amounts," Mel Spigelman, president and CEO of TB Alliance, told DW.

The New York-based Global Alliance for TB Drug Development is a non-profit organization dedicated to the development of new tuberculosis medicines.

According to Spigelman, "especially the drug rifampicin, which is part of the standard treatment against TB, causes a large number of these interactions with many of the antiretroviral drugs against HIV."

A new drug combination created by TB Alliance could tackle this problem. "Right now we have not found any interactions that would limit our ability to use the drugs together," Spigelman said.

Shorten TB therapy

According to the World Health Organization WHO, more than eight million people fall ill with TB every year and over a million of them die. "HIV and TB form a lethal combination, each speeding the other's progress," WHO states on its website. "TB is a leading killer of people living with HIV, causing one fifth of all deaths."

The TB drug combination called PaMZ has just completed phase II of its clinical trial. In the trial researchers compared the new drug combination to the standard treatment. One fifth of the test persons were infected with HIV.

"The results show PaMZ killed more TB bacteria in patients than standard therapy and did so at a faster rate," the researchers announced in Melbourne. They predicted that their medication could shorten TB therapy to four months - and also cut the costs to a fraction of the present ones.

At the moment, TB treatment takes at least half a year. In the case of multi-drug-resistant tuberculosis, it can take up to two years, during which a patient undergoes extensive chemotherapy, including injections, which can have many side effects.

Even some forms of resistant strains are killed

"PaMZ is basically three separate antibiotics which we had combined, starting years ago, in the test tube and then in animals," Spigelman says.

One of the substances, pyrazinamide, is part of the current TB standard treatment, while the other two, PA-824 and moxifloxacin, are new drug candidates. The three antibiotics can be combined in one pill.

Researchers say the new drug combination will not only kill drug-sensitive but also some of the multi-drug-resistant TB bacteria. By definition multi-drug-resistant tuberculosis does not respond to at least isoniazid and rifampicin, the two most powerful anti-TB drugs.

About 450,000 people worldwide develop this form of TB, and Spigelman believes a third of these patients could be treated with the new drug. "However, some drug-resistant TB is also resistant to either pyrazinamide or moxifloxacin, two of the drugs that we do use," he says, adding that for these patients, one would need even newer drugs, which TB alliance hopes to bring on the market in the future.

Money urgently needed

The third and last phase of the clinical drug trial, which could start by the end of this year, will span some 50 study sites across Africa, Asia, Eastern Europe, and Latin America.

"But that is not completely certain because we are still in the process of raising the money to support the trial," Spigelman says. The Bill and Melinda Gates Foundation has already announced "significant funding," TB alliance said on its website, but that is not enough to finance a very expensive phase III trial. "From an ethical point of view, we cannot start a clinical trial until we have guarantees that we will have the resources to finish it," Spigelman says.

Hence, in April Bill Gates called on other organizations to support the trial financially. "The results from early phase research suggest that this new drug regimen could provide the breakthrough we need to accelerate progress against this deadly and dangerous disease," Gates said.