Patients with HIV who do not carry the HLA-B*5701 allele are at very low risk for a hypersensitivity reaction to the antiviral drug abacavir, researchers reported.
For that reason, a pharmacogenetic test—screening for the HLA-B*5701 variant—now can be used to prevent a specific toxic effect of a drug, according to Dr. Simon Mallal of Royal Perth (Australia) Hospital and his associates.
The investigators conducted the Prospective Randomised Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) in 1,956 adults with HIV who were treated at 265 medical centers in 19 countries. A total of 847 patients who served as the control group began usual treatment with abacavir without HLA-B*5701 screening. Participants' mean age was 42 years, with a range of 18–76 years.
Another 803 patients first underwent HLA-B*5701 screening, and those who were found to carry the variant were excluded from abacavir therapy. Their mean age was 42 years, with a range of 18–77 years. The remaining HLA-B*5701-negative patients received abacavir. Both groups were observed over 6 weeks for hypersensitivity reactions.
No hypersensitivity reactions developed in patients who were not carriers of HLA-B*5701. In the control group, approximately half of the patients later found to be HLA-B*5701 carriers had a hypersensitivity reaction to the drug.
The HLA-B*5701 allele had a negative predictive value of 100% and a positive predictive value of 48%, Dr. Mallal and his associates said (N. Engl. J. Med. 2008;358:568–79).
“HLA-B*5701 carriage clearly demarcated a high-risk group of patients, accounting for approximately 6% of the population, from the remaining 94% who were at low risk for a hypersensitivity reaction to abacavir,” they said.
The study was supported by GlaxoSmithKline, and several of the investigators disclosed relationships with the company. Dr. Mallal disclosed that he is the sole shareholder for a company that has a patent pending for HLA-B*5701 testing.