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

<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls.<h4>Conclusion</h4>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.