Rifampin acceptable in some TB/HIV instances

Skeptical clinicians say rifabutin is fine, thanks

When rifampin recently was restored to the armamentarium of clinicians treating TB patients on protease inhibitors for their HIV, the occasion didn’t exactly excite the world of HIV therapy.1 It did, however, serve to remind everyone of just how complicated the jobs of infectious disease specialists have become.

In the past, rifampin, a pillar of TB treatment today, had not been recommended in instances in which patients were concurrently taking other drugs — in particular, protease inhibitors — that interact with it. Physicians contacted about the government update giving them permission to use rifampin, at least in certain situations, say they’re not planning to make any sudden moves, new guidelines or not.

"With all the new antiviral agents, things have gotten really complicated," says Elena Hollender, MD, director of clinical services at the A.G. Holley Hospital in Lantana, FL. "We spend most of our time walking on tiptoes as it is already. I think in this case, most of us would say, Tread cautiously.’"

The update, published in the Centers for Disease Control and Prevention’s March 10 Morbidity and Mortality Weekly Report, tells clinicians they now can use rifampin in the following three situations:

• in patients whose antiretroviral regimen includes efavirenz, a non-nucleoside reverse transcriptase inhibitor, and two nucleoside reverse transcriptase inhibitors (NRTIs);

• in patients whose antiretroviral regimes include the protease inhibitor ritonavir and one or more NRTIs;

• in patients whose antiretroviral regimen includes the combination of the two protease inhibitors ritonavir and saquinavir in either the hard-gel or soft-gel formulation.

The update also strongly recommends the following:

• reducing the dose of rifabutin to 150 mg two or three times per week when it’s given to patients taking ritonavir, with or without saquinovir in either the hard or soft formulation;

• increasing the dose of rifabutin to either 450 mg or 600 mg daily, or 600 mg two or three times a week, when rifabutin is used concurrently with efavirenz.

Although it’s always good to have another option, Hollender says she’s grown comfortable working with rifabutin and plans to stick with it. "It’s nice to have another choice," she says. "And there may well be a place for rifampin in certain situations. But personally, I would like to see more data about dosage adjustments."

True, rifabutin costs about $4 more per dose than rifampin, but conventional wisdom dictates that not having to worry about side effects more than makes up for the extra cost. Arguments for trying rifampin probably would be more compelling if rifabutin were causing problems, but it isn’t, says Hollender. "There’s no problem with tolerability, and from what we know about the mechanism of the drug, it should have about the same efficacy."

Rick O’Brien, MD, chief of the Research and Evaluation Branch of the Centers for Disease Control and Prevention’s Division of TB Elimination, agrees. "I don’t treat HIV patients in my practice, but I can tell you that rifabutin is a good drug," he says. "It’s generally well-tolerated; in fact, it may be a bit better tolerated than rifampin. Plus, we’ve got good data on its efficacy. It’s actually got a slightly longer half-life than rifampin."

Anyone who wants to give rifampin a try in one of the new combinations listed in the update, Hollender says, should monitor blood levels of the drugs as a safety net. "We already have patients on whom we do this, both for their TB drugs and their protease inhibitors. With the advent of people perhaps turning to ritonavir or saquinovir, there may be another role for drug monitoring."


1. Centers for Disease Control and Prevention. Notice to readers: Updates guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR 2000; 49:185-189.