Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis
Multidrug resistant tuberculosis (tuberculosis resistant to rifampin and isoniazid) is a growing public health threat and may be particularly lethal among patients infected with HIV.2 Although knowledge of the metabolic pathways of some second-line drugs (e.g. ethionamide, cycloserine, para-amino salicylate) is incomplete because many of these drugs were developed and licensed decades ago, it is believed (based on knowledge of chemical structure, metabolic pathways, and/or metabolism of related agents) that most of these drugs do not have significant drug-drug interactions with antiretrovirals. The second-line aminoglycoside antituberculosis drugs (capreomycin, kanamycin, and amikacin) are primarily renally excreted as unchanged compounds and are unlikely to have metabolic drug interactions with antiretrovirals. Fluoroquinolones (like ofloxacin, moxifloxacin, or levofloxacin) are also unlikely to have significant drug interactions with antiretrovirals. Since patients with multidrug-resistant tuberculosis do not receive rifampin, the risk of clinically-significant drug interactions is markedly reduced. However, overlapping toxicities such as nephrotoxicity, QT prolongation on the electrocardiogram, psychiatric side effects, and gastrointestinal intolerance may limit options for co-treatment of HIV and multidrug-resistant tuberculosis.