Abacavir is a nucleoside reverse transcriptase inhibitor used for combination antiretroviral therapy for treating human immunodeficiency virus (HIV) infection. An adverse effect from abacavir is a treatment-limiting hypersensitivity reaction, which can be severe and potentially life-threatening. Abacavir-induced hypersensitivity reaction has been associated with the presence of the major histocompatibility complex class I allele HLA-B*5701. A screening test for the HLA-B*5701 allele can assist clinicians to identify patients who are at risk of developing a hypersensitivity reaction to abacavir.
Abacavir hypersensitivity reaction affects 5 to 8% of patients and can be observed during the first 6 weeks of antiretroviral therapy  . Symptoms of an abacavir hypersensitivity reaction include skin rash, fever, malaise, gastrointestinal symptoms, and respiratory symptoms. Severe forms of the skin rash may result in Stevens-Johnson Syndrome, toxic epidermal necrolysis, or systemic lupus erythematosus  . If a patient experiences a hypersensitivity reaction, abacavir is discontinued and symptoms generally resolve within 72 hours  . Restarting abacavir is contraindicated as it can result in a potentially life-threatening reaction and even death  . The HLA-B*5701 screening test minimizes potential toxicities to abacavir by identifying patients who may be at risk of developing a hypersensitivity reaction.
Sequence-based genotyping and polymerase chain reaction (PCR) sequencing of specific oligonucleotide probes are the most widely used techniques. To test for the HLA-B*5701 allele, a blood or saliva specimen is collected. The genetic sequences coding for the HLA-B*5701 are probed and reported as positive if the allele is present, or negative if the allele is absent.
Public Health Importance
There are approximately 33 million people worldwide who are living with HIV/AIDS  ; among them are approximately 1.2 million Americans, with an estimated 56,300 newly diagnosed infections each year. The Centers for Disease Control and Prevention (CDC) estimates that 21% of HIV-positive people are unaware that they are infected  . Combination antiretroviral therapy is the most effective pharmacotherapy for HIV treatment  . Minimizing adverse effects of antiretroviral therapy is critical to controlling the infection and maintaining treatment adherence.
Published Reviews, Recommendations and Guidelines
Systematic evidence reviews
Recommendations by independent group
Guidelines by professional groups
Analytic Validity : Test accuracy and reliability in measuringthe HLA-B*5701 allele (analytic sensitivity and specificity).
Clinical Validity : Test accuracy and reliability in predicting abacavir hypersensitivity (predictive value).
Clinical Utility : Net benefit of test in improving health outcomes
We acknowledge Sara Bedrosian, BA, BFA and William D. Dotson, PhD from the CDC for reviewing this document and providing comments.
This project was funded in part by the CDC Cooperative Agreement #1U38GD000070, Pharmacogenomics Education Program (PharmGenEd™): Bridging the Gap between Science and Practice. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of CDC.
The authors have declared that no competing interests exist.
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