HLA-B*5701 clinical testing: early experience in the United States

Abstract

HLA-B*5701 testing to provide risk stratification for abacavir hypersensitivity has the potential to reduce incidence of hypersensitivity reactions in susceptible individuals. Early experience with clinical HLA-B*5701 testing of the first 100 specimens, from a large clinical reference laboratory in the United States, is presented. Patient samples were tested using a two-step approach. The first step allowed rapid identification of most HLA-B*5701-negative samples in a high throughput mode. The second step involved resolution of putative positives by DNA sequencing to identify B*5701 specifically as well as other B57 subtypes. Test reporting included a phone call from a genetic counselor to obtain the ethnic background and indication for testing and to provide a patient-specific interpretation. The patients population was comprised of Caucasians, 84%; Hispanics, 13%; and African Americans, 3%. Among the 100 samples tested, 92% were HLA-B*5701-negative and 8% were positive for the HLA-B*5701 allele. All HLA-B*5701 allele positives were identified in Caucasian patients. Where the indication for testing was obtainable (57 patients), pre-abacavir therapy screening was the indication 67% of the time. Clarification of previous suspected history of hypersensitivity was the indication 33% of the time. Among samples tested to help clarify a previous history of hypersensitivity, 16/19 or 84% did not carry the HLA-B*5701 allele whereas 3/19 (16%) were carriers of the HLA-B*5701 allele. Early utilization of HLA-B*5701 testing in community practice was not always consistent with the clinical indications for testing. Post-test communication assisted in providing physician education and interpretation of patient-specific results.

Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility

“…LabCorp, a major centralized clinical laboratory in the United States with extensive expertise in HLA genotyping, developed an HLA-B*5701 assay in response to a request from HIV health-care providers. 25 While prospective HLA-B*5701 screening significantly reduced the rate of ABC HSR in these three published reports, these studies raised some important concerns for GSK, assuming the link between HLA-B*5701 and ABC HSR to be true. First, two subjects in the Western Australian cohort who were HLA-B*5701 positive experienced ABC HSR because the subjects' HLA-B genotype results were not reviewed prior to initiation of ABC.…”

Professional Perspectives About Pharmacogenetic Testing and Managing Ancillary Findings

“…Geneticists can play a key role in the development of such education efforts, and our small cohort of geneticists agreed that this was an appropriate role for their profession. Strengthening partnerships with local genetic specialists as well as with testing laboratories may not only help facilitate uptake of new PGx tests (Faruki et al, 2007) but also provide guidance regarding the management of potential ancillary information.…”

Clinical Delivery of Pharmacogenetic Testing Services: A Proposed Partnership Between Genetic Counselors and Pharmacists

“…This type of counseling may be described as “one size fits all” and can be beneficial when dealing with a high volume of patients across all medical specialties and even direct-to-consumer [23]. This type of service is exemplified by one U.S. laboratory’s experience in the introduction of the PGx test HLA-B*5701 for the HIV drug abacavir [30]. When the test result was sent back to the ordering physician, a genetic counselor would place a follow-up call to provide a “patient-specific interpretation,” considering the patient’s ethnicity and discussing treatment management plans [30].…”