Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis

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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 Vitria MD, Department of HIV/AIDS, World Health Organization, Geneva, Switzerland