rifampin and Immune-System-Diseases

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

Topics: Antitubercular Agents; Ethambutol; Humans; Immune System Diseases; Isoniazid; Latent Tuberculosis; Liver; Liver Cirrhosis; Liver Diseases; Liver Failure; Liver Function Tests; Liver Transplantation; Prevalence; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant

Access to antiretroviral therapy is rapidly expanding in resource-limited settings, where tuberculosis is the most common opportunistic infection. Coadministration of antitubercular and antiretroviral agents is, therefore, occurring commonly, and it is associated with 3 major complications. First, induction of cytochrome P-450 enzymes and P-glycoprotein by rifampin results in reduced concentrations of nonnucleoside reverse-transcriptase inhibitors and, particularly, protease inhibitors. This potentially results in the loss of antiviral efficacy and the development of viral resistance. Replacing rifampin with rifabutin, which does not significantly affect the concentrations of antiretroviral agents, is advocated but is currently unaffordable in resource-limited settings. Second, overlapping toxicities of antitubercular and antiretroviral agents occur frequently, necessitating discontinuation of therapy and increasing the risk of nonadherence. Third, immunopathological reactions, termed "the immune reconstitution inflammatory syndrome," occur frequently when antiretroviral therapy is initiated in patients with tuberculosis. These complexities of coadministration of antitubercular and antiretroviral agents are reviewed, and research priorities are highlighted.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 Enzyme System; Developing Countries; Drug Interactions; Drug Resistance, Viral; Enzyme Induction; HIV; Humans; Immune System Diseases; Inflammation; Protease Inhibitors; Reverse Transcriptase Inhibitors; Rifampin; Rifamycins; Tuberculosis