Twice-weekly RIF/PZA may get nod as six months of INH gets more respect
Writing group labors over final details of CDC/ATS preventive therapy
As TB experts continued sorting out the details of what will become the new guidelines for preventive therapy, two new additions to the still-evolving document had emerged. First, twice-weekly rifampin/pyrazinamide (RIF/PZA), not listed as an option in earlier drafts, got to come in from the cold; second, six months of isoniazid (INH), formerly relegated to a footnote, made it back on the table of numbered options.
If those changes stick, it would mean the list of choices for treatment of latent TB would include all of the following: nine months of INH, either daily or twice-weekly; six months of INH, either daily or twice-weekly; two months of daily RIF/PZA; two months of twice-weekly RIF/PZA; and, in certain situations, four months of rifampin (RIF).
The "writing group" charged with working out the details is composed of TB experts from the Atlanta-based Centers for Disease Control and Prevention (CDC) and from the American Thoracic Society. The document is due out in about six months.
Many TB controllers said they were pleased with the changes. "Wow! That really makes my day," says David Ashkin, MD, medical adviser to Florida’s TB control program. Ashkin will use the twice-weekly short-course regimen in controlled clinical trials in the state. "It makes total sense, but it needs more study, which is exactly what we’re doing. I’m glad they approved it."
Probably no one has lobbied harder for twice-weekly RIF/PZA than Richard Chaisson, MD, assistant professor of medicine at Johns Hopkins University in Baltimore. "I assumed they’d endorse this regimen to begin with, and I was shocked when they didn’t," he says.
There are two reasons Chaisson says he’d like to get his hands on the regimen. First, it’s by far the most feasible way to get preventive therapy into a population of injecting drug users (IDUs) in Baltimore; in the community setting, direct observation of IDUs would be hard to pull off more than twice a week, he says.
And among the prison population — the second group targeted as a top priority for preventive therapy — more than twice-weekly would be virtually impossible, he adds. "Prisoners are an important population," he says. "But at the detention center here in Baltimore and in the state prison system as well, providing anything on a daily basis is very, very difficult, which is why I’ve lobbied so hard for this."
In Massachusetts, where TB controllers have targeted the foreign-born (not IDUs or prisoners) for preventive therapy, it’s a different story. Given PZA’s reputation for unpleasant side effects and the longstanding reluctance of most foreign-born communities to buy into the notion of any kind of preventive therapy, Nardell thinks four months of RIF is the logical first choice.
"From the standpoint of compliance, we haven’t had any more success with RIF/PZA than with six months of INH," says Nardell. "People here simply don’t seem to be tolerating it very well. Four months of rifampin, on the other hand, seems acceptable on every count, so why make us go through the back door to get to it? Why save it for special occasions?"
Complexity issues still troubling to some
Foreign-trained physicians and their foreign-born patients have a tough time accepting American beliefs about skin testing, the BCG vaccine, and regular isoniazid prophylaxis. Does throwing in a long list of new options, some complicated by potential side effects, sound like a good idea? Nardell thinks not.
As long as he has access to twice-weekly RIF/PZA, Chaisson says he has no reservations at all about four months of RIF. "Of course, there’s only that one study of the Chinese silicotics," he says. "But to me, four months of rifampin is a perfectly fine regimen." For that matter, he adds, why not just three, which was the duration of the Hong Kong trial?
The decision to put the four months of RIF into a special-occasions straitjacket because it lacks sufficient data credentials is especially needling to Nardell. "When you confine your choices exclusively to this evidence-based’ medicine, you can tie yourself in knots," he says. Better to let a little common sense prevail, he adds.
Chaisson says he’s sympathetic, seeing as how twice-weekly RIF/PZA was probably snubbed the first time out because it had never gone head-to-head in a clinical trial against the daily form of the regimen.
Insiders at the CDC allow that if Chaisson had made it to the first working group, twice-weekly RIF/PZA probably would have been on the list from the start. As fate would have it, Chaisson was stuck in Baltimore, laboring over a grant application involving a trial of — you guessed it — twice-weekly RIF/PZA. He got the grant.
As for six months of INH (both twice-weekly and daily variations look set to get the nod), that shift is one most clinicians seem to endorse without reservations.
"There’s been a lot of debate over this," says Chaisson. "Health departments say, Gee, six months is already too much work; no way we can do nine.’" Others argue that from the standpoint of an individual patient, it’s clear nine months is better.
Both sides are correct, Chaisson points out; but what the data show, he adds, is that what’s best for one patient doesn’t work as well in an entire program. It follows that the best choice is to provide lots of choices, so programs and individual physicians can make their own decisions, he adds.
The thought of so many choices still gives Nardell the fidgets. "First they tell us treatment of latent TB should go out of the public health clinic and into the community," he grumbles. "Then they give us not one option, but three or four. In the community setting, that’s too complicated — more complicated drugs to learn about and more drugs, period."
Chaisson disagrees. "I worry when I hear people say make it real simple,’" he says. "You do that, and you lose options."
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