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Managing Drug Interactions in the
Treatment of HIV-Related
Tuberculosis
Rifabutin and Antiretroviral
Drugs
Rifabutin is as effective for tuberculosis treatment
as rifampin 38, 39, but has much less effect on drugs metabolized
through the CYP3A system 40 (Table 3). However, rifabutin is either
not available or is very expensive in countries with high rates of HIV-related
tuberculosis. Furthermore, some antiretroviral drugs have a substantial effect
on rifabutin concentrations, necessitating somewhat complex dosing guidelines
for rifabutin in the setting of antiretroviral therapy (see Table 3). In addition
to their complexity, there is another potential problem of using rifabutin for
tuberculosis treatment. If a patient whose rifabutin dose was decreased in
response to antiretroviral therapy then stops taking the interacting drug (e.g.,
ritonavir), the resulting rifabutin concentrations are likely to be sub-therapeutic.
These factors, in addition to the limited availability of the drug, limit the
use of rifabutin in the treatment of HIV-related tuberculosis.
Rifabutin and Protease
Inhibitors
Rifabutin has little, if any effect on the serum concentrations
of protease-inhibitors (other than unboosted saquinavir) 22. Cohort
studies have shown favorable virological and immunological outcomes of protease-inhibitor-based
antiretroviral therapy in the setting of rifabutin-based tuberculosis treatment
1, 41. Though no comparative studies have been done, the combination
of rifabutin (if available) with protease-inhibitor based antiretroviral therapy
is the preferred form of therapy for patients unable to take NNRTI-based antiretroviral
therapy (Table 1). As above, there are concerns about the safety of super-boosted
protease-inhibitors and the efficacy of nucleoside-only regimens in the setting
of rifampin-based tuberculosis treatment.
The protease-inhibitors, particularly if pharmacologically
boosted with ritonavir, markedly increase serum concentrations and toxicity
of rifabutin 42. Therefore, the dose of rifabutin should be decreased
when used with protease-inhibitors (Table 3). As above, the decreased dose
of rifabutin would be sub-therapeutic if the patient stopped taking the protease-inhibitor
without adjusting the rifabutin dose. Therefore, adherence to the protease-inhibitor
should be assessed with each dose of directly observed tuberculosis treatment;
one convenient way to do so is to give a supervised dose of protease-inhibitor
at the same time as the directly observed dose of tuberculosis treatment.
Last Reviewed: 05/18/2008 Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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