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TNF, LTA, HSPA1L and HLA-DR gene polymorphisms in HIV-positive patients with hypersensitivity to cotrimoxazole.

Authors
Journal
Pharmacogenomics
1462-2416
Publisher
Future Medicine
Publication Date
Disciplines
  • Biology
  • Ecology
  • Geography

Abstract

AIMS: Sulfamethoxazole in combination with trimethoprim (cotrimoxazole) is used for prophylaxis and treatment of several opportunistic infections in HIV-infected patients. It is associated with a high incidence of hypersensitivity reactions, which is thought to have an immune basis. Genetic polymorphisms in MHC are known to predispose to hypersensitivity reactions to a structurally diverse group of drugs in HIV-positive patients. The aim of the study was to determine whether functional polymorphisms in TNF, LTA, HSPA1L and HLA-DRB1 genes influence the risk of cotrimoxazole hypersensitivity in HIV-infected patients. METHODS: We genotyped 136 HIV-positive patients with (n = 53) and without (n = 83) cotrimoxazole hypersensitivity using a combination of PCR-based techniques, including PCR-restriction fragment length polymorphisms, PCR-sequence specific oligonucleotides and real-time PCR. Genotypes and the haplotype frequencies were analyzed using the chi(2) test in the Haploview and CLUMP programs. Results: No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls. CONCLUSION: Our data show that MHC polymorphisms are not major predisposing factors for cotrimoxazole hypersensitivity, although we cannot exclude a minor contribution. An environmental factor (i.e., HIV infection) seems to predominate over any of the genetic factors so far investigated in increasing the risk of cotrimoxazole hypersensitivity.

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