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

Pharmacogenomics. 2009 Apr;10(4):531-40. doi: 10.2217/pgs.09.6.


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.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / genetics
  • AIDS-Related Opportunistic Infections / microbiology
  • Anti-Infective Agents / adverse effects*
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / therapeutic use
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / genetics
  • Female
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins / genetics
  • Haplotypes
  • Humans
  • Lymphotoxin-alpha / genetics
  • Male
  • Pneumocystis carinii / isolation & purification
  • Pneumonia, Pneumocystis / drug therapy*
  • Pneumonia, Pneumocystis / genetics
  • Pneumonia, Pneumocystis / microbiology
  • Polymorphism, Restriction Fragment Length*
  • Polymorphism, Single Nucleotide*
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacokinetics
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use
  • Tumor Necrosis Factor-alpha / genetics


  • Anti-Infective Agents
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Trimethoprim, Sulfamethoxazole Drug Combination