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


CONCLUSIONS
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.
Department of Pharmacology & Therapeutics, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, Merseyside, L69 3GE, UK.
Ana
A
Alfirevic
F Javier
FJ
Vilar
Mohammed
M
Alsbou
Ansar
A
Jawaid
Wendy
W
Thomson
William E R
WE
Ollier
Clive E
CE
Bowman
Olivier
O
Delrieu
B Kevin
BK
Park
Munir
M
Pirmohamed
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000235:genetics; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D045363:Pneumocystis carinii / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000890:Anti-Infective Agents; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D015662:Trimethoprim, Sulfamethoxazole Drug Combination