Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis

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Introduction

Worldwide, tuberculosis is the most common opportunistic infection among people with HIV infection. In addition to its frequency, tuberculosis is also associated with substantial morbidity and mortality. Despite the complexities of treating two infections requiring multidrug therapy at the same time, antiretroviral therapy can be life-saving among patients with tuberculosis and advanced HIV disease. Observational studies in a variety of settings have shown that use of antiretroviral therapy during tuberculosis treatment results in marked decreases in the risk of death or other opportunistic infections among persons with tuberculosis and advanced HIV disease ^{1, 2}.

Concomitant use of treatment for tuberculosis and antiretroviral therapy is complicated by the adherence challenge of polypharmacy, overlapping side effect profiles of antituberculosis drugs and antiretroviral drugs, immune reconstitution inflammatory syndrome, and drug-drug interactions ³.The key interactions, and the focus of this document, are those between the rifamycin antibiotics and four classes of antiretroviral drugs: protease inhibitors, non-nucleoside reverse-transcriptase inhibitors [NNRTI], CCR5-receptor antagonists, and integrase inhibitors ³. Only two of the currently available antiretroviral drug classes, the nucleoside analogues (other than zidovudine ⁴) and enfuvirtide (a parenteral entry inhibitor) do not have significant interactions with the rifamycins.

The purpose of this summary is to provide the clinician with updated recommendations for managing the drug-drug interactions that occur when using antiretroviral therapy during tuberculosis treatment. Changes from previous versions of these guidelines include: an effort to obtain and summarize the clinical experience of using specific antiretroviral regimens during tuberculosis treatment (not just pharmacokinetic data), a table summarizing the clinical experience with key antiretroviral regimens and providing recommended regimens (Table 1), and sections on treatment for special populations (young children, pregnant women, patients with drug-resistant tuberculosis). We include drug-drug interaction data for antiretroviral drugs that have been approved or currently available through expanded access programs in the United States; these recommendations will be updated as additional antiretroviral drugs progress become available.