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Managing Drug Interactions in the
Treatment of HIV-Related
Tuberculosis
Limitations of these
Guidelines
The limitations of the information available for writing
these guidelines should be appreciated. First, drug-drug interaction studies are often
done among healthy volunteers. While such studies reliably predict the nature
of a drug-drug interaction (e.g., that rifampin decreases the serum concentrations
of efavirenz), they seldom provide the optimal management of that interaction
among patients with HIV-related tuberculosis (in cases of extreme interactions,
such as that between rifampin and unboosted protease-inhibitors, the data from
healthy volunteers can be definitive). In this update of the guidelines we
emphasize studies done among patients with HIV-related tuberculosis, particularly
those that evaluate treatment outcomes of the two diseases. However, such studies
often had small sample sizes, limiting the generalizability of their findings.
Second, rates of drug metabolism often differ markedly between individuals,
and part of that variance may be due to genetic polymorphisms in drug-metabolizing
enzymes. Therefore, drug interactions and their relevance may not be the same
in different populations. Third, in the attempt to provide the most up-to-date
information we include studies that have been presented at international conferences,
but that have not yet completed the peer review process and been published.
Fourth, it is very difficult to predict the outcome of complex drug interactions,
such as those that might occur when three drugs with CYP3A activity are used
together (e.g., rifabutin, atazanavir and efavirenz). Therapeutic drug monitoring,
if available, may be helpful in such situations. Finally, in the Special Populations
section, we highlighted the lack of pharmacokinetic data on two key populations
of patients with HIV-related tuberculosis – pregnant women and children. We
provide recommendations for these key populations, but these are based primarily
on expert opinion because of the lack of pharmacokinetic data.
Writing group
These guidelines were written by William Burman MD (Denver Public Health) and
then reviewed and revised with comments from:
Elaine Abrams, MD, Harlem Hospital and the Columbia University School of Public
Health, New York City, NY, USA
Debra Benator,MD, Washington DC Veterans Administration Medical Center, Washington,
DC, USA
David Burger, PharmD, PhD, Radboud University Medical Center Nijmegen, Nijmegen,
the Netherlands
Mark Cotton, MD PhD, Stellenbosch University, Tygerberg, South Africa
Diane Havlir, MD, University of California – San Francisco, San Francisco CA,
USA
Gary Maartens, MD, University of Cape Town, Cape Town, South Africa
Jose Miro MD, Hospital Clinic Universitari, Barcelona, Spain
Charles Peloquin, PharmD, National Jewish Medical
and Research Center, Denver, CO, USA
Fabio Scano, Stop TB Partnership, World Health Organization, Geneva,
Switzerland
Timothy Sterling MD, Vanderbilt University, Nashville, TN, USA
Andrew Vernon, MD, Centers for Disease Control and Prevention, Atlanta, GA,
USA
Marco Vitória MD, Department
of HIV/AIDS, World Health Organization, Geneva, Switzerland
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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