Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations.
Abacavir is an effective antiretroviral drug used to treat HIV-1 infection. Approximately 5% of patients treated with abacavir develop a hypersensitivity reaction that requires discontinuation of the drug. In an initial pharmacogenetic study conducted in a predominantly White male population, multiple markers in the human leukocyte antigen (HLA)-B chromosomal region were associated with hypersensitivity to abacavir. The HLA-B*5701 association has now been confirmed in White males in a subsequent, larger study (n=293, p=4.7 x 10(-18)) and is also observed in White females (n=56, p=6.8 x 10(-6)) and Hispanics (n=104, p=2.1 x 10(-4)). HLA-B*5701 was not associated with hypersensitivity in Blacks (n=78, p=0.27). HLA-B*5701 alone lacks sufficient predictive value to identify patients at risk for hypersensitivity to abacavir across diverse patient populations. Efforts are ongoing to identify markers with sufficient sensitivity and specificity to be clinically useful. Even after a marker set is identified, appropriate clinical identification and management of hypersensitivity to abacavir must remain the cornerstone of clinical practice.
Hughes
Arlene R
AR
GlaxoSmithKline, NC 27709, USA. arh48207@gsk.com
Mosteller
Michael
M
Bansal
Aruna T
AT
Davies
Kirstie
K
Haneline
Stephen A
SA
Lai
Eric H
EH
Nangle
Keith
K
Scott
Trevor
T
Spreen
William R
WR
Warren
Liling L
LL
Roses
Allen D
AD
D019380:Anti-HIV Agents / Q000009:adverse effects*; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People / Q000235:genetics; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D005819:Genetic Markers; D015235:HLA-B Antigens; D014409:Tumor Necrosis Factor-alpha; D000099227:Abacavir