HLA-B*5701 screening for hypersensitivity to abacavir.
BACKGROUND
Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir.


METHODS
This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701-positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir.


RESULTS
The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001).


CONCLUSIONS
HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)
Mallal
Simon
S
Royal Perth Hospital and Murdoch University, Perth, Australia. s.mallal@murdoch.edu.au
Phillips
Elizabeth
E
Carosi
Giampiero
G
Molina
Jean-Michel
JM
Workman
Cassy
C
Tomazic
Janez
J
Jägel-Guedes
Eva
E
Rugina
Sorin
S
Kozyrev
Oleg
O
Cid
Juan Flores
JF
Hay
Phillip
P
Nolan
David
D
Hughes
Sara
S
Hughes
Arlene
A
Ryan
Susanna
S
Fitch
Nicholas
N
Thorborn
Daren
D
Benbow
Alastair
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000099227:Abacavir
D015224:Dideoxynucleosides; D005819:Genetic Markers; D015235:HLA-B Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen