Severe Systemic Hypersensitivity Reaction Research Articles

Anaphylaxis biomarkers: present and future.

Anaphylaxis is a severe, rapidly developing, and life-threatening systemic hypersensitivity reaction. The diagnosis of anaphylaxis is primarily clinical. Numerous studies on the mechanisms and the biomarkers of the disease are initiated every year. The biomarkers of anaphylaxis may become an important tool for the diagnosis, prevention, repeated risk assessment, severity stratification, and new therapeutic strategies for treatment of the disease. Various immune and non-immune mediators produced and released by effector cell populations are currently considered as biomarkers of anaphylaxis. Here, we review the current data on potential biomarkers of anaphylaxis and the possibilities and perspectives for their use in future clinical practice.

Death Due to Furosemide Anaphylaxis and The Importance of Serum Tryptase Level in Diagnosing Anaphylaxis: A Case Report

Anaphylaxis is a severe systemic hypersensitivity reaction with a sudden onset and may result in death. In this study, we report the case of a 71-year-old female patient who died within seconds after the administration of intravenous furosemide in emergency service; she had high serum tryptase levels at postmortem examination and nonspecific findings at autopsy, and death due to anaphylaxis was reported. With this study, we wanted to point to the rare and potentially fatal drug anaphylaxis, such as furosemide anaphylaxis. Also, our results indicate the importance of serum tryptase levels in the diagnosis of death due to anaphylaxis.

Management of Suspected Life-Threatening Perioperative Anaphylaxis and Risk Factors for Near-Fatal and Fatal Outcomes: A Retrospective Study in China.

Perioperative anaphylaxis (POA) is an acute severe systemic hypersensitivity reaction characterized by life-threatening respiratory and circulatory collapse. In our previous study, we reported the epidemiology of suspected POA in China. In the present study, we aimed to elucidate the management and outcomes of these cases and further verify the risk factors for near-fatal and fatal outcomes. This was a retrospective study of 447 cases of suspected life-threatening POA encountered at 112 tertiary hospitals in mainland China between September 2018 and August 2019. Patient characteristics, symptoms, duration of hypotension, treatments, and clinical outcomes were documented. Bivariate logistic regression was used to identify risk factors for near-fatal and fatal outcomes. Most cases of suspected POA (89.9%) were recognized and treated within 5 min. Epinephrine was administered as the initial treatment in 232 (51.9%) cases. Corticosteroids (26.6%), other vasoactive drugs (18.3%), and bronchodilators (1.6%) were also administered as the initial treatment instead of epinephrine. The initial dosage of epinephrine (median, 35 µg) was insufficient according to the anaphylaxis guidelines. On multivariable analysis, age ≥65 years (odds ratio [OR] 7.48; 95% confidence interval [CI]: 1.33-41.87, P=0.022), ASA physical status IV (OR 17.68; 95% CI: 4.53-68.94; P<0.001), and hypotension duration ≥15 min (OR 3.63; 95% CI: 1.11-11.87; P=0.033) were risk factors for fatal and near-fatal outcomes. Most cases in this study were managed in a timely manner, but the epinephrine application should be optimized according to the guidelines. Age ≥65 years, ASA physical status IV, and long-term hypotension were risk factors for near-fatal and fatal outcomes.

Current situation of anaphylaxis in Japan: Data from the anaphylaxis registry of training and teaching facilities certified by the Japanese Society of Allergology – secondary publication

BackgroundAnaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. MethodsBetween February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. ResultsThis study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. ConclusionsThe present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.

IDIOPATHIC ANAPHYLAXIS: A DIAGNOSTIC CHALLENGE

<h3>Introduction</h3> Anaphylaxis is the most severe systemic hypersensitivity reaction which is potentially fatal. Its true prevalence is underestimated due to the variabilty of clinical presentation and different definitions in various guidelines. Details of the episode and risk factors are often not available from medical record. Serum Tryptase is rarely ordered at the time of initial presentation. <h3>Case Description</h3> 43 year-old female healthcare worker presented with genralized hives with pruritus, palpiations and racing heart, dizziness, shortness of breath on her way home from work in the evening. She had two episodes of diarrhea and somehow managed to climb 20 steps to her apartment where she collapsed soon after. She self-medicated with Benadryl and did not seek medical help. she had two further episodes 6 weeks and 3 months later. There was no hsitory food ingestion in the past 8 hours. She did not drink alcohol or use NSAIDS. No history of Insect sting. She had no history of atopy, food or drug allergy. None of these episodes were related to menstruation. She was on Amlodipine for Hypertension but no other medication and was otherwise in good health. Baseline Tryptase, 24 hour urinary 5-HIAA, N-methylhistamine, Metanephrines were normal. <h3>Discussion</h3> Idiopathic Anaphylaxis was diagnosed, and self-injectable Epinephrine was prescribed. Patient was educated about the serious nature of her condition, the use of Epinephrine and advised to seek medical help in an emergency. A note was givento patient to present ER Physician, to get Tryptase levels should another episode occur.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

What’s Eating You? Mosquitoes (Culicidae)

Mosquito bites cause a variety of reactions ranging from pruritic papules to severe systemic hypersensitivity reactions. The salivary glands of mosquitoes have been found to contain more than 70 different allergens. Herein, we describe the pathophysiology and clinical appearance of mosquito bite reactions as well as proper management of this condition.

Predictors of serious outcomes among patients with anaphylaxis seen in the Philippine national tertiary hospital.

BackgroundAnaphylaxis is a severe and life-threatening systemic hypersensitivity reaction. The incidence of anaphylaxis has increased significantly in recent years.ObjectiveTo identify predictors of serious outcomes among patients with anaphylaxis seen in the national tertiary hospital of the Philippines from 2015 to 2019.MethodsData was collected retrospectively through search of the medical records section and census reports on all patients diagnosed with anaphylaxis seen at the national tertiary hospital from 2015 to 2019. The patients’ clinical profile, management, and outcome were extracted. Multiple logistic regression analysis was used to determine the association of clinical characteristics and physicians’ management with the development of serious outcomes. Variable selection procedure through backward elimination method was used to determine significant predictors of serious outcomes of anaphylaxis. Data analysis was done using Stata 14 software.ResultsThere were 300 patients with anaphylaxis seen at the Philippine national tertiary hospital from 2015 to 2019. Of the 300 patients, 179 were female (57.9%). The median age of the patients was 26 years old, with an interquartile range of 33 years. Only 75 patients (25%) had a past history of allergic disease. Majority of the patients (70%) had comorbidities. Drugs were the most common trigger of anaphylaxis (81.3%). Antibiotics were the most common type of drugs implicated (27%). Serious outcomes were noted in a total of 31 patients (10.3%). The significant predictors of serious outcomes in anaphylaxis are age (p = 0.034) and cofactors including use of beta-blockers and presence of acute infection (p < 0.001).ConclusionIn the Philippine national tertiary hospital, the incidence of anaphylaxis increased by 240% in the past decade. Predictors of serious outcome in anaphylaxis include increased age and presence of cofactors such as beta-blocker use and presence of acute infection.

Anaphylaxis.

Anaphylaxis is the most severe systemic hypersensitivity reaction, and it can be life-threatening or even fatal. It involves the activation of multiple immune and non immune pathways beyond IgE, thus exhibiting different phenotypes. New symptoms of hypersensitivity caused by chemotherapy drugs, monoclonal antibodies, and biological agents have been suggested to be recognized as anaphylaxis phenotypes. No biomarker has been described that allows an unequivocal diagnosis of anaphylaxis. Moreover, more biomarkers for specific endotypes are needed to stratify severity, to predict risk, and to optimaze tretament choice in the individual patient. Food, drugs and stinging insects represent the most commly identified triggers. Idiopathic anaphylaxis is a diagnosis of exclusion and it can hide a clonal mast cell disorder. Individual risk factors and co-factors may influence the severity of anaphylaxis or its onset, and they should be identified to implement the appropriate measures to prevent recurrence. Prompt recognition and treatment are critical in anaphylaxis, adrenaline being the first-line saving therapy. Individualized anaphylaxis action plan should include avoidance measures, prescription of an adrenaline autoinjector, education, optimal management of relevant comorbidities, venom specific immunotherapy, food oral immunotherapy, and drug desensitization, when appropriate. However, the quality of acute and long-term anaphylaxis management is variable influencing the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but they often prove challenging to implement in routine clinical care.

The role of IgE specific for galactose-\u03b1-1,3-galactose in predicting cetuximab induced hypersensitivity reaction: a systematic review and a diagnostic meta-analysis

Recombinant monoclonal antibodies are used for treating various diseases, from asthma, rheumatoid arthritis, and inflammatory bowel disease to cancer. Although monoclonal antibodies are known to have fewer toxic reactions compared with the conventional cytotoxic antineoplastic drugs, the cases of severe systemic hypersensitivity reaction (HSR) should be acknowledged. Our aim was to assess the diagnostic accuracy of the anti-IgE for galactose-α-1,3-galactose in patients with HSRs to cetuximab. We searched in PubMed, Cochrane Library, Scopus, and World of Science databases to July 1st, 2020. We included a total of 6 studies, with 1074 patients. Meta-analysis was performed using bivariate analysis and the random-effect model. The pooled sensitivity was 73% (95% CI 62–81%) and the pooled specificity was 88% (95% CI 79–94%). We had not found significant heterogeneity and, despite some discrepancies in the nature of data available in the analysed studies, we draw the conclusion that the presence of cetuximab specific IgE (anti cetuximab antibody) and/or galactose-α-1,3-galactose shows moderate to high sensitivity and specificity of developing an HSR. More studies are needed to establish a protocol necessary for the proper prediction and avoidance of HSR related to cetuximab.

Surprises of food anaphylaxis: a clinical case

Anaphylaxis is a severe systemic hypersensitivity reaction that is characterized by rapid onset and life-threatening respiratory and blood circulation problems. We present to your attention a clinical case of the polyvalent allergy development in a three-year-old child with repeated episodes of food anaphylaxis. The child was born and he constantly lives in central Russia, but has a profile of sensitization unusual for a Ural resident. The clinical case is described in detail in order to demonstrate the stages of a child’s life, on which sensitization was likely to be first formed, and later the manifestation of clinical symptoms arose. Determination of the sensitization profile by means of the component allergy diagnostics methods (ISAC, ImmunoCAP) showed that the boy is sensitized to a large number of food allergens, including milk and egg proteins; storage proteins for peanuts, soy, hazelnuts and sesame; proteins related to the nsLTP-proteins. The obtained results made it possible to recognize and differentiate true IgE-mediated sensitization, to propose the optimal therapeutic tactics and to select an elimination diet. Application of molecular allergy diagnostic methods is useful in clinical practice in case of patients with multivalent sensitization and a history of severe allergic reactions.

936. Body Fat Redistribution/Accumulation, Pancreatic Disorders, Musculoskeletal Disorders, IRIS, Severe Systemic Rash and Hypersensitivity Reactions Following Initiation of Commonly Prescribed Antiretrovirals

BackgroundDolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), and darunavir (DRV) are commonly used for the treatment of HIV. We assessed the frequency of 6 select disorders after prescription of DTG-, EVG-, RAL-, or DRV-based regimens.MethodsHIV-positive patients in the OPERA® Observational Database initiating DTG-, EVG-, RAL-, or DRV-containing regimens were included. Disorders of interest were body fat redistribution/accumulation, pancreatic disorders, and musculoskeletal disorders, as defined in Figures 2–3, as well as immune reconstitution inflammatory syndrome (IRIS), severe systemic rash and hypersensitivity reaction (HSR). Baseline patient characteristics and disorder history were described. The proportion of patients with disorders of interest during follow-up were compared between core agents for each disorder. All events occurring during follow-up were considered prevalent, while incident disorders excluded patients with any history of disorder. To account for multiple comparisons, the Sidak Correction was applied (adjusted α level: 0.017).ResultsOut of 22,674 patients, 7,860 (35%) initiated DTG, 9,738 (43%) EVG, 1,600 (7%) RAL, and 3,477 (15%) DRV. Baseline demographic and clinical characteristics varied by core agent initiated (Figure 1). Compared with DTG, history of body fat redistribution/accumulation was less frequent in patients initiating EVG, and more frequent in patients initiating RAL (Figure 2). EVG users also had a lower prevalence during follow-up than DTG users (Figure 3). However, there was no difference in new onset of body fat redistribution/accumulation between groups (Figure 3). No difference in prevalent or incident pancreatic or musculoskeletal disorders was detected between core agents (Figure 3). IRIS, severe systemic rash, and HSR occurred in no more than 2 patients per core agent group, with no difference detected between groups.ConclusionIncident body fat redistribution/accumulation, pancreatic disorders, musculoskeletal disorders, IRIS, severe systemic rash, and HSR were rare in this large cohort of patients initiating DTG, EVG, RAL, or DRV. Despite some channeling of patients with a disorder history towards DTG and RAL use, the likelihood of new events did not differ by core agent. Disclosures L. Brunet, Epividian, Inc.: Employee, Salary. ViiV Healthcare: ViiV Healthcare has contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck: Merck has contracted research with my employer, Epividian, Inc., Employer received funding for other research. J. Fusco, Epividian, Inc.: Employee, Salary. ViiV Healthcare: Viiv Healthcare contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck & Co.: Merck contracted research with my employer, Epividian, Inc., Employer received funding for research. V. Vannappagari, ViiV HealthCare: Employee, GlaxoSmithKline Company Stock and Salary. L. Ragone, ViiV Healthcare: Employee and Shareholder, restricted shares and Salary. G. Fusco, Epividian, Inc.: Employee, Salary. ViiV Healthcare: Viiv Healthcare contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck & Co.: Merck contracted research with my employer, Epividian, Inc., Employer received funding for research.

Anaphylaxis and anaesthesia

No abstract available.

Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disorder of abnormal mast cells in at least 1 extracutaneous organ/tissue. Anaphylaxis is an acute, severe systemic hypersensitivity reaction, and a strong association between SM and anaphylaxis has been shown. However, not all patients with SM experience anaphylaxis. Presently, there are no predictive markers to discriminate patients with SM at high risk of anaphylaxis from those at low risk. This study sought to determine risk factors for the occurrence of anaphylaxis in patients with SM. A cross-sectional study was conducted in 122 consecutive adult patients with SM admitted to the Mastocytosis Center at Karolinska University Hospital. All patients underwent medical evaluation, including bone marrow biopsy and a thorough allergy workup. To determine risk factors, study subjects were categorized into 2 groups according to the presence (n= 55) or absence (n= 67) of anaphylaxis and compared for their demographic, clinical, and biochemical characteristics. Patients with SM with anaphylaxis had less frequent presence of mastocytosis in the skin (P < .001), more atopic predisposition (P= .021), higher total IgE levels (P < .001), and lower baseline tryptase levels (27 ng/mL vs 42 ng/mL; P= .024) compared with patients with SM without anaphylaxis. Patients with SM with anaphylaxis display unique clinical and laboratory features. Hence, a risk analysis tool that is capable of discriminating patients with SM at high risk of anaphylaxis from those at low risk with 86% sensitivity was developed by using the variables male sex, absence of mastocytosis in the skin, presence of atopy, IgE levels of 15 kU/L or more, and baseline tryptase levels of less than 40 ng/mL.

A Pilot Study of Intralymphatic Immunotherapy for House Dust Mite, Cat, and Dog Allergies.

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.

The role of viral infection in the development of severe drug eruptions

The role of viral infections in the development of drug allergy has recently received increasing attention. Evidence is accumulating that immune responses to drugs can be profoundly influenced by herpesvirus infection that occurs before, concurrent with, or subsequent to drug administration. The current advances in our understanding of the role of viral infections in drug eruptions have been sparked by recent studies on human herpesvirus 6 (HHV-6) reactivation in severe systemic hypersensitivity reactions to drugs, eventually referred to as drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia with systemic symptoms (DRESS). It becomes clear that HHV-6 is not the only herpes virus reactivated during the course of DiHS and other herpes viruses are also reactivated in sequence as shown in graft-versus-host disease (GVHD), which can explain frequent deterioration or several flare-ups of clinical symptoms occurring after withdrawal of the causative drug in DiHS. Here we describe how sequential reactivations of herpesviruses occur during the course of DiHS and discuss how the reactivation events could influence the initiation and maintenance of drug-specific immune responses, resulting in severe immunopathology.

Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe systemic hypersensitivity reaction caused by specific drugs, in which herpesvirus reactivations and organ dysfunction occur during the course of the disease. Although recent reports have documented the development of autoimmune disease after complete resolution of DIHS/DRESS, relatively little is known about long-term outcomes after complete resolution of the disease. The aim of this study was to retrospectively analyze complications and sequelae in the early and late phases of DIHS/DRESS according to treatment. In all, 34 patients were classified into 2 groups: 14 patients with oral corticosteroid treatment; and 20 with noncorticosteroid treatment. The disease time course was divided into 2 periods: the first 6 months after onset of the drug reaction (early phase); and the period thereafter (late phase). Investigations to detect the presence of viral/bacterial infectious diseases, organ dysfunction, and autoantibodies were performed in both early and late phases. Herpesvirus infections and pneumonia were detected in 6 and 2 patients, respectively, in the corticosteroid treatment group in the early phase. In the noncorticosteroid treatment group, 2 patients developed autoimmune diseases, namely lupus erythematosus and autoimmune thyroiditis. Autoantibodies were detected in 44.4% of patients examined in the late phase of the disease. This study only evaluated a small number of autoantibodies. The need for anti-inflammatory effects from systemic corticosteroids should be balanced with the risk of infectious diseases and the benefits of preventing the appearance of later autoimmune conditions in patients with DIHS/DRESS.

A Randomised Controlled Trial of Two Infusion Rates to Decrease Reactions to Antivenom

BackgroundSnake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions.Methods and FindingsThis was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell’s viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20–25 min) versus 120 min (IQR:75–120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:−10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94).ConclusionsA slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms.Trial Registration www.slctr.lk SLCTR/2007/005

Anaphylactoid reaction after injection of ketorolac in a loading dose for patient-controlled analgesia -A case report-

Anaphylaxis is a severe and life-threatening systemic hypersensitivity reaction. Ketorolac is a popular drug used for patient-controlled analgesia. Although anaphylactic reaction to ketorolac has not been frequently reported, it can develop by way of several mechanisms. A 41-year-old male patient was scheduled for laparoscopic correction of a perforated gastric ulcer. Emergency surgery was performed under general anesthesia with no complications. Near the end of anesthesia administration, ketorolac in a loading dose was administered intravenously in order to launch patient-controlled analgesia. Following injection, urticaria-like skin lesions, including rashes and wheels appeared systemically; tachycardia and breathing difficulty with oxygen desaturation also developed. Through additional inquiry into the patient's drug history, past experience with ibuprofen allergy was identified. Antihistamine, steroid, and aminophylline were administered, and continuous positive airway pressure by full facial mask was applied to relieve bronchospastic symptoms. The patient recovered without further complications.

The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV

To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States. Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction among patients taking abacavir testing HLA-B*5701 positive and negative were from the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial study. The monthly costs of abacavir-based and tenofovir-based regimens were $1135 and $1139, respectively; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis. Simulated cohort of patients initiating HIV therapy. The interventions are first-line abacavir, lamivudine, and efavirenz without pretreatment HLA-B*5701 testing; the same regimen with HLA-B*5701 testing; and first-line tenofovir, emtricitabine, and efavirenz. Quality-adjusted life years and lifetime medical costs discounted at 3% per annum, cost-effectiveness ratios ($/QALY). Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted quality-adjusted life years, and $472,200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at an incremental cost of $110, resulting in a cost-effectiveness ratio of $36,700/QALY compared with no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving quality-adjusted life expectancy. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701. Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment.