montelukast and HIV-Infections

To report the case of an HIV patient who developed neuropsychiatric disturbances when montelukast was added to her therapy containing efavirenz.. A 41-year-old woman with HIV infection had been on treatment with efavirenz, emtricitabine, and tenofovir disoproxil fumarate since 2007 with good tolerance. In November 2011, montelukast was started for asthma and shortly thereafter neuropsychiatric symptoms appeared, consisting of disturbed sleep, vivid dreams, irritability, confusion, and concentration difficulties. In January 2012, 2 months after the introduction of montelukast, she continued to report unbearable symptoms without any improvement; so, montelukast was withdrawn and the psychiatric symptoms completely disappeared.. The combination of efavirenz and montelukast has not previously been associated with any pharmacokinetic interactions or worsening of neuropsychiatric symptoms. This case report indicates the possibility of adverse effects developing when the 2 drugs are used together. These symptoms might either be related to a drug-drug interaction or increased by the similar side effect profiles of the 2 drugs. The higher score on the Karch-Lasagna scale suggests that an adverse effect is the more likely explanation. We cannot, however, rule out a drug interaction, given that efavirenz inhibits the CYP 2C9, 2C19, and 3A4 isoenzymes and CYP 3A4, 2C9, and 2C8 are involved in the metabolism of montelukast.. Considering that efavirenz is frequently used in antiretroviral therapy and that neuropsychiatric symptoms can limit its use, clinicians should consider the possibility of worsening of these symptoms, such as mood disorders and abnormal dreams, when montelukast is introduced.

Topics: Acetates; Adult; Alkynes; Anti-Asthmatic Agents; Anti-HIV Agents; Asthma; Benzoxazines; Cyclopropanes; Drug Interactions; Female; HIV Infections; Humans; Neurotoxicity Syndromes; Quinolines; Sulfides

Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

Topics: Acetates; Anti-Retroviral Agents; Antineoplastic Agents; Biopsy; CD4 Lymphocyte Count; Cyclopropanes; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Jaundice, Obstructive; Leukotriene Antagonists; Liver; Liver Function Tests; Male; Middle Aged; Quinolines; Sarcoma, Kaposi; Skin Neoplasms; Sulfides; Treatment Outcome; Viral Load

The ATP binding cassette (ABC)-transporters are energy dependent efflux pumps which regulate the pharmacokinetics of both anti-cancer chemotherapeutic agents, e.g. taxol, and of human immunodeficiency virus-1 (HIV-1) protease inhibitors (HPIs), e.g. saquinavir. Increased expression of several ABC-transporters, especially P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), are observed in multidrug resistant (MDR) tumor cells and on HIV-1 infected lymphocytes. In addition, due to their apical expression on vascular endothelial barriers, both P-gp and MRP2 are of crucial importance towards dictating drug access into sequestered tissues. However, although a number of P-gp inhibitors are currently in clinical trials, possible inhibitors of MRP2 are not being thoroughly investigated. The experimental leukotriene receptor antagonist (LTRA), MK-571 is known to be a potent inhibitor of MRP transporters. Using the MRP2 over-expressing Madin-Darby canine kidney cell line, MDCKII-MRP2, we evaluated whether the clinically approved LTRAs, e.g. montelukast (Singulair) and zafirlukast (Accolate), can similarly suppress MRP2-mediated efflux. We compared the efficacy of increasing concentrations (20-100 microM) of MK-571, montelukast, and zafirlukast, in suppressing the efflux of calcein-AM, a fluorescent MRP substrate, and the radiolabeled [(3)H-] drugs, taxol and saquinavir. Montelukast was the most potent inhibitor (p<0.01) of MRP2-mediated efflux of all three substrates. Montelukast also increased (p<0.01) the duration of intracellular retention of both taxol and saquinavir. More than 50% of the drugs were retained in cells even after 90 min post removal of montelukast from the medium. Our findings implicate that montelukast, a relatively safe anti-asthmatic agent, may be used as an adjunct therapy to suppress the efflux of taxol and saquinavir from MRP2 overexpressing cells.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Antineoplastic Agents, Phytogenic; Biological Transport; Cell Line; Chemotherapy, Adjuvant; Cyclopropanes; Dogs; Drug Resistance, Neoplasm; Drug Resistance, Viral; Fluoresceins; HIV Infections; HIV Protease Inhibitors; Indoles; Leukotriene Antagonists; Multidrug Resistance-Associated Proteins; Neoplasms; Paclitaxel; Phenylcarbamates; Propionates; Quinolines; Saquinavir; Sulfides; Sulfonamides; Time Factors; Tosyl Compounds

Topics: Acetates; Antiretroviral Therapy, Highly Active; Cyclopropanes; HIV Infections; Humans; Immune System Diseases; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Syndrome

The pathogenesis of immune reconstitution disease (IRD) is not well understood and it can be difficult to manage. Leukotrienes exert proinflammatory effects, have an important role in the innate immune response, and are relatively deficient in HIV infection. Montelukast is a leukotriene receptor antagonist (LTRA) currently licensed for the treatment of asthma. We report a series of three patients with severe HIV associated IRD (cases 1 and 2 associated with starting HAART and unresponsive to steroids), who obtained clinically dramatic responses to treatment with montelukast. The first case is of IRD to secondary syphilis and the second and third to tuberculosis. Cases 1 and 3 both relapsed after a temporary break from montelukast and resolved on restarting. Montelukast should be considered in HIV associated IRD as an alternative to steroids and where these are not effective. Leukotriene overactivity may be implicated in IRD.

Topics: Acetates; Adjuvants, Immunologic; Cyclopropanes; Female; HIV Infections; Humans; Immune System Diseases; Male; Quinolines; Sulfides