title: Monitoring adverse drug reactions to sulfonamide antibiotics in human immunodeficiency virus-infected individuals.
abstract: Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.
authors.affiliation: Department of Pharmacology, University of Toronto, Canada. manuela@sten.sunnybrook.utoronto.ca
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.forename: Izabella M
authors.initials: IM
authors.lastname: Malkiewicz
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Phillips
authors.forename: Anita R
authors.initials: AR
authors.lastname: Rachlis
authors.forename: Debra
authors.initials: D
authors.lastname: Ong
authors.forename: Elaine
authors.initials: E
authors.lastname: Yeung
authors.forename: Neil H
authors.initials: NH
authors.lastname: Shear
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D004342:Drug Hypersensitivity; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D007202:Indicators and Reagents; D013449:Sulfonamides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination