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New Drug Regimen Speeds TB Treatment

Three-drug combo more effective than standard therapy

An experimental cocktail of three drugs can dramatically shorten the time it takes to treat patients infected with tuberculosis (TB) strains that are hard to cure with conventional antibiotics, according to new research presented July 21 at the 20th International AIDS Conference in Melbourne, Australia.

Dubbed the PaMZ regimen, the drug combo killed more TB bacteria than standard therapy and at a faster rate in a phase IIb trial, investigators said.

If funding is found, PaMZ will move to phase III tests by the end of the year.

Physicians are concerned about the emergence of TB that fails to respond to frontline antibiotics. These resistant strains are especially dangerous for people co-infected with the human immunodeficiency virus (HIV), which attacks CD4 immune cells, leaving the body exposed to opportunistic microbes.

The PaMZ regimen consists of two candidate drugs that are not yet approved for the treatment of TB — Pa-824 and moxifloxacin — in combination with an existing treatment, pyrazinamide. The therapy, which is administered as tablets, was formulated specifically for patients believed to have TB strains that can be targeted by these drugs.

The new study involved testing PaMZ against standard drugs — isoniazid, rifampicin, pyrazinamide, and ethambutol — in 207 volunteers in South Africa, a fifth of whom were co-infected with HIV. Of these, 181 were sensitive to the PaMZ drugs, whereas 26 were multidrug-resistant (MDR).

In the study, 71% percent of subjects treated with PaMZ were cleared of TB bacteria in their sputum within 2 months compared with 38% of those receiving standard therapy.

The MDR subjects all received PaMZ and were treated within 4 to 6 months compared with 2 years for standard treatment. This should translate into cost savings of more than 90% in some countries as MDR therapy is complex and labor-intensive, the investigators said.

In addition, PaMZ did not interfere with antiretrovial treatments commonly used to suppress HIV infection.

At least a third of the approximately 35 million people with HIV infection worldwide also have TB in its latent form, meaning that they have the Mycobacterium TB germ that causes the disease but do not have symptoms of illness, according to the World Health Organization (WHO).

People co-infected with both TB and HIV are nearly 30 times more likely to develop active TB than are those without HIV. In 2012, approximately 320,000 people died of HIV-associated TB, the WHO said.

Source: Medical Xpress; July 21, 2014.

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