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Immunogenicity of trimethoprim‐sulfamethoxazole in SIV‐infected rhesus macaques
Author(s) -
Wong Yat Yee,
Watson Kal,
Trepanier Lauren
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb631
Subject(s) - simian immunodeficiency virus , trimethoprim , peripheral blood mononuclear cell , antibody , immunology , virology , pharmacology , medicine , biology , in vitro , virus , microbiology and biotechnology , antibiotics , biochemistry
HIV infected patients have a high risk of hypersensitivity (HS) reactions to trimethoprim/sulfamethoxazole (TMP/SMX). To understand this, simian immunodeficiency virus (SIV)‐infected rhesus macaques were used to explore possible metabolic and immunologic risk factors. SIVmac239‐infected male macaques and non‐infected controls were administrated TMP/SMX (120 mg/kg/day) for 14 days. Prior to dosing, plasma was assayed for antioxidants and cytokines, needle liver biopsies were collected for expression arrays, and PBMC were isolated for in vitro toxicity assays. After treatment, urine was collected for SMX metabolites, plasma was analyzed for anti‐drug antibodies, PBMC were tested for drug specific T cells, and lymph node and plasma were assayed for drug adducts. 7 SIV‐infected and 4 control animals have been treated to date. Baseline plasma ascorbate and red cell glutathione were not significantly different between groups. SMX hydroxylamine was significantly more toxic towards PBMC from SIV‐infected animals (37%) compared to controls (2%; P = 0.04). One SIV‐infected monkey developed an erythematous rash on day 7, and was positive for anti‐SMX antibodies; 3 additional monkeys showed T cells reactive to SMX‐nitroso or TMP. These preliminary data suggest that TMP/SMX is immunogenic in macaques as in humans, and that signs consistent with sulfonamide HS may be possible in this model. Funded by R01 GM100784.