In HIV Patients, Isoniazid-Rifapentine Combo Dramatically Cuts TB Prophylaxis Therapy

March 19, 2019

By Gene Emery

NEW YORK (Reuters Health) - Preventing tuberculosis with one month of daily treatment with an isoniazid-rifapentine combination is no less effective than nine months of daily isoniazid therapy in people with HIV, according to a new open-label trial published in Thursday's New England Journal of Medicine.

Of the 3,000 volunteers enrolled in the randomized study and followed for at least three years, 2% were diagnosed with tuberculosis or died from the disease regardless of which of the two regimens they followed. The risk of side effects was comparable in both groups.

More importantly, while 90% of the people getting isoniazid for nine months completed their treatment, the rate was 97% in the group getting two drugs for one month (P<0.001).

Both the treatments worked whether or not the patient had a latent TB infection.

"This is really good news," said coauthor Dr. Richard Chaisson, a professor of medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

In an accompanying editorial, Dr. Matthew Saunders and Dr. Carlton Evans of Imperial College London write, "These data show that tuberculosis can be effectively prevented with a 1-month regimen and add to the growing number of alternatives to traditional isoniazid monotherapy for preventing tuberculosis. These alternatives include isoniazid and rifapentine administered weekly for 3 months, 3 months of daily isoniazid and rifampin, and 4 months of daily rifampin monotherapy."

About 30 million people worldwide are infected with HIV and face a higher risk for tuberculosis. Fewer than a million people a year get preventive treatment. As a result, about 1,000 people with HIV die from TB each day.

Twenty-three percent of the patients in the new study - which included adults and children over 12 - had a positive test for latent tuberculosis. People with known or suspected active TB were excluded. The rifapentine dose was adjusted by weight.

Patients assigned to the one-month group were actually given eight weeks to take all their pills and people assigned to nine-months of treatment were given 54 weeks so they could resume their therapy if side effects became too severe.

Shorter treatments should improve compliance rates and the new results reinforce that idea. While only 1% of patients in the one-month group discontinued therapy because of toxic effects, the rate was 2% in the nine-month group.

The rates of side effects grade 3, 4 or 5 were 3% in both groups. Neutropenia ranked grade 3 or higher was seen in 2% of the one-month group and 1% of the nine-month group.

One problem with this shorter treatment is the cost of rifapentine, especially when TB is a bigger problem in poorer countries.

"Given the abundant evidence for the efficacy of rifapentine-containing regimens, advocacy to reduce the cost of this medicine should be supported and scaled up to improve access for patients who are most likely to benefit," Drs. Saunders and Evans say in their editorial.

However, it's not clear if the one-month regimen will be as effective in people without HIV. As much as one-quarter to one-third of the world's population harbor an asymptomatic latent TB infection.

"It's something that hopefully will be useful for anyone at risk for developing TB, but it really needs to be studied in other populations," Dr. Chaisson told Reuters Health by phone.

"We had the experience a number of years ago of having a treatment we studied first in people with HIV that got the treatment down to 2 months," he said. "And then when we started using it in people without HIV, it proved to be highly toxic for reasons that nobody could really understand. We're hoping in the future to get a study of HIV-negative people at high risk, and to look at children and pregnant women."

The study, conducted at 45 sites in 10 countries, was known as BRIEF TB/A5279.

SOURCE: https://bit.ly/2HmGOtC

N Engl J Med 2019.

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