Abacavir hypersensitivity reaction
- Elizabeth J Phillips, MD, FRCPC, FRACP
Elizabeth J Phillips, MD, FRCPC, FRACP
- Professor of Medicine and Pharmacology
- Vanderbilt University Medical Center
- Simon A Mallal, MBBS, FRACP, FRCPA
Simon A Mallal, MBBS, FRACP, FRCPA
- Major E.B. Stahlman Professor of Infectious Diseases
- Director, Center for Translational Immunology and Infectious Diseases
- Director, Center for AIDS Research
- Director, Vanderbilt Technologies for Advanced Genomics
- Vanderbilt University School of Medicine
- Director, Institute for Immunology & I
Abacavir is a guanosine nucleoside analog with potent activity against HIV. However, in the premarketing phase of drug development, multiple reports emerged of a hypersensitivity syndrome associated with abacavir, which led to significant morbidity. Rare reports of mortality were associated with failure to recognize this clinical syndrome as drug hypersensitivity.
Research into this syndrome has demonstrated a host predisposition to this drug-associated hypersensitivity reaction, which is based on immunogenetics . Subsequent studies have demonstrated improved drug safety when abacavir use is restricted to patients without this genetic predisposition. This is the first time that an immunogenetic marker has been used in clinical practice to prevent a specific drug toxicity.
This topic will address the epidemiology, immunogenetics, clinical manifestations, clinical management, and screening recommendations for the abacavir hypersensitivity reaction (AHR). Indications for use of abacavir as part of combination antiretroviral therapy (ART) are discussed elsewhere. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
The term "human leukocyte antigen (HLA) system" is synonymous with the human major histocompatibility complex (MHC). These terms describe a group of genes on chromosome 6 that encode a variety of cell surface markers, antigen-presenting molecules, and other proteins involved in immune function. The HLA region is divided into three classes and there are three different class I antigens (HLA-A, -B, -C). (See "Human leukocyte antigens (HLA): A roadmap".)
The principal task of the immune system is to recognize and respond to potential pathogens without reacting to the normal components of the individual. Class I HLA molecules present peptide fragments of foreign antigens to CD8+ T cells, which generally have cytotoxic/suppressor function. (See "Major histocompatibility complex (MHC) structure and function".)
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- GENERAL BACKGROUND
- IMMUNOGENETIC BASIS FOR AHR
- EPIDEMIOLOGY OF AHR
- Clinical diagnosis of AHR
- Association of AHR and race
- EVIDENCE OF LINK BETWEEN HLA BACKGROUND AND AHR
- Carriage rates of HLA-B*57:01 and risk of AHR
- Testing performance among different racial populations
- CLINICAL SYNDROME
- AVAILABLE TESTING METHODS FOR AHR
- Sensitivity and specificity of HLA-B*57:01 screening
- Skin patch testing
- DIFFERENTIAL DIAGNOSIS
- CLINICAL MANAGEMENT
- EARLY STUDIES OF IMMUNOGENETIC SCREENING
- CLINICAL TRIALS OF HLA-B*57:01 SCREENING
- PREDICT-1 trial
- ARIES trial
- SCREENING PRIOR TO ABACAVIR EXPOSURE
- Whom to screen
- Role of skin patch testing
- MONITORING OF PATIENTS ON ABACAVIR
- LABORATORY TESTING AND QUALITY ASSURANCE
- FUTURE RESEARCH
- SUMMARY AND RECOMMENDATIONS