Study raises hope for new drugs for resistant tuberculosis

A new combination of three drugs killed 99 percent of patients' tuberculosis bacteria in two weeks, raising hope for a new weapon against increasingly resistant forms of TB.

The midstage study, presented on Monday at the International AIDS Conference in Washington, needs to be confirmed in larger and longer trials. Scientists say the drug cocktail could speed treatment and help reduce the emergence of resistant forms of tuberculosis.

"TB is the largest killer of AIDS patients, and so in order to contain the AIDS epidemic, we have to contain TB to a much greater extent," said Dr. Mel Spiegelman, chief executive officer of the TB Alliance, a non-profit research group that conducted the study, which was published in the Lancet.

The combination of drugs includes one existing TB drug, pyrazinamide, a repurposed antibiotic from Bayer AG called moxifloxcin that is now used off-label for patients with drug-resistant TB, and a new drug called PA-824 being developed by the New York-based TB Alliance.

What the combination lacks are any drugs in the class called rifamycins, which pose the greatest threat of side effects for patients who also are being treated for infections with HIV, the human immunodeficiency virus that causes AIDs.

"The results of this clinical trial give us the first indication that a new TB drug regimen - a combination of drugs - could be more effective than any of the existing TB drug regimens," Spiegelman said.

He said the combination is especially promising because it could be used to treat patients with both treatment-sensitive TB and TB strains that are resistant to two or more of the common drugs, known as multiple-drug resistant TB.

The findings come as the TB bacterium Mycobacterium tuberculosis is rapidly developing resistance to the world's most effective tools.

Standard treatments falter

Standard treatment for TB usually includes a mix of four drugs over a period of six months and multi-drug resistant TB can take 18 to 24 months to treat.

Since most of the disease is cleared in the first few months, people often do not finish their full regimen of TB drugs, which can lead to drug resistance, making TB more dangerous and more difficult to treat.

According to the World Health Organization, in some parts of the world, one in four people with TB has a form of the disease that can no longer be treated with standard drug cocktails.

Even more deadly forms of TB are emerging. Dr. Zarir Udwadia of the National Hospital in Mumbai, India, has identified more than a dozen cases of TB that cannot be killed by any existing form of treatment.

TB kills an estimated 1.4 million people each year, and some 9 million people are newly infected.

In the midstage study conducted at two sites in South Africa, researchers tested the drug combination on 85 patients with TB. After two weeks, they found the new treatment combination was 99 percent effective at killing off TB bacteria in these patients.

A follow-up study of the treatment testing the drug combination over a two-month period already has begun and should be completed next year, Spiegelman said. Once that study is done, the group hopes to start large-stage clinical trials.

"The results look strongly promising from this early trial," Dr. Mario Raviglione, director of the World Health Organization's Stop TB Partnership, said in a statement.

"If further trials hold up, we may have a major solution for drug-sensitive TB and drug-resistant TB."

The study was funded by the Bill & Melinda Gates Foundation, the U.S. Agency for International Development and the British and Irish governments.

Besides the promise of a new treatment for TB, the design of the trial, which tested several combinations of drugs at once to find the most effective treatment, may help advance the study of other TB treatments, Raviglione said.