Abacavir Prescription Research Articles

Prevalence of Abacavir Hypersensitivity Reaction and Cost-Effectiveness of HLA-B*5701 Screening: A Ten-Year Experience in The HRH Princess Maha Chakri Sirindhorn Medical Center

Background: Recently, the authors had reported a case with abacavir hypersensitivity reaction (ABC-HSR), the first diagnosed patient at the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC). There was no data regarding the incidence or prevalence of ABC-HSR previously reported in Thailand. Objective: To study the prevalence of ABC-HSR, the abacavir use pattern and the cost effectiveness for the routine human leukocyte antigen (HLA)-B*5701 screening before abacavir use by analyses of the MSMC data. Materials and Methods: All patients at the MSMC who were prescribed abacavir from October 1, 2010 to September 30, 2020 were retrospectively reviewed for ABC-HSR and the abacavir use pattern at the time when abacavir was started. The cost-effectiveness analysis was applied by analyzing the cost between the routine HLA-B*5701 screening before abacavir use and the HLA-B*5701 confirmation for ABC-HSR. The cost for the prevention of a case of ABC-HSR was defined. Results: There were total of 54 patients who were prescribed abacavir and only one ABC-HSR case diagnosed. The prevalence of ABC-HSR was 1.85%. The main reason for the abacavir prescription was a substitution for tenofovir (TDF) because of the TDF adverse effects (81.13%). The HLA-B*5701 screening before abacavir use was done in 26.42% at the MSMC. If all eligible patients were routinely screened for the HLA-B*5701 allele before abacavir use, the cost would be 54,000 Baht. The cost for the diagnosis and the management of the ABC- HSR case was 7,230 Baht. The cost for the prevention of a case of ABC-HSR was 46,770 Baht. Conclusion: The prevalence of ABC-HSR was low. The main reason for abacavir use was a substitution for TDF. The cost for the prevention for a case of ABC-HSR was 46,770 Baht which would be less if the cost for the HLA-B*5701 test was reduced. Keywords: Abacavir; Hypersensitivity reaction; Prevalence; HLA-B*5701

HLA-B*5701 Genotyping for Abacavir Prescription: Re-Examination of its Cost-Effectiveness in Singapore

HLA-B*5701 Genotyping for Abacavir Prescription: Re-Examination of its Cost-Effectiveness in Singapore

Drug Hypersensitivity.

Adverse drug reactions (ADRs) can be divided into pharmacological ADRs (type A) and hypersensitivity reactions (type B). Type B reactions can be further subdivided into immediate (<1 h, urticaria, anaphylaxis) and delayed reactions (>1 h, variable manifestation like exanthema, hepatitis, cytopenias). Prevention of hypersensitivity is often still a challenge. Selective literature search in Medline and Google Scholar as well as research in ADR databases like OpenVigil or SIDER. Laboratory tests ([specific] IgE, lymphocyte transformation test), histological examination, dermatological tests (prick tests, epicutaneous testing) and-under certain circumstances-provocation tests can be used for diagnostics. There are only a few pharmacogenetic biomarkers to predict hypersensitivity reactions. Currently, testing for defined HLA genes is mandatory before prescription of abacavir and before the use of carbamazepine in Han Chinese or Thai patients. Immediate discontinuation of the trigger is essential in all allergic hypersensitivity reactions. Immediate reactions are treated with antihistamines, glucocorticoids and occasionally with epinephrine. Delayed reactions are usually treated with glucocorticoids. Careful, structured diagnostics in case of suspected hypersensitivity together with adequate documentation (allergy passport) is necessary in order to avoid incidents in patients receiving subsequent treatment. Consistent use of existing resources (diagnostics and documentation) can help to avoid hypersensitivity reactions or to rapidly recognize and treat them, respectively.

Rapid and Reliable Genotyping ofHLA-B*57:01in Four Chinese Populations Using a Single-Tube Duplex Real-Time Polymerase Chain Reaction Assay

HLA-B*57:01 is strongly associated with severe adverse drug reaction induced by the anti-HIV drug abacavir (ABC) and antibiotic flucloxacillin. This study was dedicated to establishing a new method for HLA-B*57:01 genotyping and investigating the HLA-B*57:01 distribution pattern in four Chinese populations. A single-tube duplex real-time polymerase chain reaction (PCR) system was established by combining the amplification refractory mutation system and TaqMan probe. The reliability of this assay was validated by comparing the genotyping results with those by sequence-based typing. With this assay, the distribution of HLA-B*57:01 in 354 blood samples from four ethnic groups, namely, Han, Tibetan, Uighur, and Buyei, was determined. A 100% concordance was observed between the results of real-time PCR and sequence-based typing in 50 Uighur samples. As low as 0.016 ng DNA that carried HLA-B*57:01 could be detected with this assay. HLA-B*57:01 carriers identified in 100 Northern Han Chinese, 104 Buyeis, 100 Tibetans, and 50 Uighurs were 0, 1 (0.96%), 3 (3%), and 6 (12%), respectively. The carrier rate of HLA-B*57:01 in Uighur was significantly higher than those in Northern Han (p = .001) and Buyei (p = .005). The newly established real-time PCR assay provides a rapid and reliable tool for HLA-B*57:01 allele screening before the prescription of ABC and flucloxacillin in clinical practice.

Identification of seven novel HLA class I alleles in New Zealand.

Seven new HLA class I alleles have been identified in the New Zealand population in the process of routine HLA typing and they are described here. Unusual bead positivity in Luminex typing identified potential new alleles in a bone marrow registry donor (B*40:285) and two HIV patients prior to abacavir prescription (B*14:02:09, B*41:29). In addition, four new class I alleles were identified through class I sequencing-based typing (SBT) outside of exons 2 and 3. One mutation was identified in exon 4 (new allele C*12:125) and three have been found in exon 5, an exon rarely sequenced. Two stem cell transplant recipients (B*07:02:45, C*03:279) had novel mutations in exon 5 and one was found in exon 5 of a potentially matched unrelated donor from DKMS, previously thought to be B*40:02:01 (B*40:303).

Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore?

Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.

External quality assessment of patient HLA-B*57:01 testing prior to abacavir prescription.

Hypersensitivity reactions to the drug abacavir are strongly associated with possession of HLA-B*57:01. Hence, patients with HIV/AIDS who may be prescribed abacavir should be tested for this HLA allele and the drug withheld from those that possess B*57:01. The UK National External Quality Assessment Service for Histocompatibility and Immunogenetics has operated a scheme for B*57:01 testing since 2008 which, in 2013, involved 47 participants from 12 countries. A total of 24 B*57:01-positive, 2 B*57:03-positive and 22 B*57-negative blood samples (including 2 B*58 samples) were distributed to between 28 and 47 laboratories each year over 6 years. Participants, who were unaware of the samples' HLA types, tested and reported on their B*57/B*57:01 status. A total of 1868 reports were assessed over the 6 years. Of the 880 reports on B*57:01 samples, 93.4% were correctly assigned as B*57:01, 2.8% were assigned as groups of B*57 alleles including B*57:01, and 3.3% were reported as B*57 positive only. Over the 6 years, there were four (0.46%) false B*57:01 negative reports. All the B*57:03-positive and B*57-negative samples, involving 72 and 916 assignments, respectively, were essentially reported as B*57:01 negative. Thus, there were no false B57:01 positive assignments. The reporting of B*57:01 status over the last 3 years of the scheme was 99.8% sensitive and 100% specific. Over the last year, it was 100% sensitive and 100% specific.

Impact of the Data Collection on Adverse Events of Anti-HIV Drugs Cohort Study on Abacavir Prescription among Treatment-Naive, HIV-Infected Patients in Canada

To evaluate the trends in abacavir (ABC) prescription among antiretroviral (ARV) medication-naive individuals following the presentation of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) cohort study. We conducted a retrospective cohort study of ARV medication-naive individuals in the Canadian Observational Cohort (CANOC). Between January 1, 2000, and February 28, 2010, a total of 7280 ARV medication-naive patients were included in CANOC. We observed a significant change in the proportion of new ABC prescriptions immediately following the release of DAD (-11%; 95% confidence interval [CI]: -20% to -2.4%) and in the months following the presentation of these data (-0.66% per month; 95% CI: -1.2% to -0.073%). A post-DAD presentation decrease in the odds of being prescribed ABC versus tenofovir (TDF) was observed (adjusted odds ratio, 0.72 per year, 95% CI: 0.54-0.97). Presentation of the DAD was associated with a significant decrease in ABC use among ARV medication-naive, HIV-positive patients initiating therapy.

Comprehensive evaluation of twoHLA‐B17 monoclonal antibodies for flow cytometry‐basedHLA‐B57/B58 screening prior to abacavir prescription

Hypersensitivity reactions to the drug abacavir, used to treat HIV/AIDS patients, is associated with possession of HLA-B*57:01. We have carefully assessed two commercially available HLA-B57/B58 murine monoclonal antibodies [0196HA and BIH0243 (One Lambda Inc.)] in a simple flow cytometry-based assay. The evaluation involved tests on 228 reference and random samples covering 91% of all WHO recognized HLA-A, B and C specificities. These involved donors with six different HLA-B*57 alleles and included 19 examples of B*57:01. Both antibodies unambiguously detected B57, but there were small difference in their reactivity against B57-positive non-B*57:01 samples. Importantly, there was no reactivity against B57/B58-negative samples. The possible amino acid motifs involved in the reactivity of these antibodies with B57/B58 were delineated. Thus, HLA-B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by a DNA-based typing method to identify B*57:01.

A case of adverse drug reaction induced by dispensing error

ObjectiveTo report about a case of acute renal failure due to absence of communication between physician and patient. Case summaryA 78 year old man with human immunodeficiency virus (HIV) accessed our hospital and was brought to our attention in August 2011 for severe renal failure. Clinical history revealed that he had been taking highly active antiretroviral therapy with lamivudine/abacavir and fosamprenavir since 2006. In April 2011 due to an augmentation in creatinine plasma levels, a reduction in lamivudine dosage to 100 mg/day and the prescription of abacavir 300 mg/day became necessary.Unfortunately, the patient took both lamivudine and abacavir therefore the association of the two medications (lamivudine/abacavir) lead to asthenia and acute renal failure within a few days. ConclusionsThis case emphasizes the importance about how physicians must pay very careful attention during drug prescription, most particularly, as far as elderly patients are concerned. In fact, communication improvement between physicians and patients can prevent increase of adverse drug reactions related to drug dispensing, with consequential reduction of costs in the healthcare system.

A Case of Hypersensitivity Reaction Induced by Abacavir in an AIDS Patient

Abacavir is a nucleoside reverse transcriptase inhibitor that is commonly used in HIV-infected patients. A well-known and potentially life-threatening side effect of abacavir is allergic hypersensitivity reaction. A screening test for the HLA-B*5701 allele is currently used to predict the risk of hypersensitivity reaction to abacavir. This test, however, may be less useful in Korea, because of the low prevalence of HLA-B*5701. A 52-year-old male with HIV infection was referred to our hospital because of suspected side-effects of antiviral agents and lymph node enlargement of the neck. He suffered from a fever, generalized edema, skin rash of the whole body, and difficulty breathing after starting antiviral agents. Suspected as a hypersensitivity reaction resulting from drug side-effects, prescription of abacavir was stopped. The patient subsequently recovered. The presence of the HLA-B*5701 allele was confirmed by polymerase chain reaction-sequencing based typing (PCR-SBT). (Korean J Med 2012;83:136-140)

Hypersensitivity reactions to HIV therapy

Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions.

A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO).Methods A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009.Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro-specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens-Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%.Conclusions Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies.

Implementation of HLA-B*5701 genetic screening prior to abacavir prescription in Georgia

Implementation of HLA-B*5701 genetic screening prior to abacavir prescription in Georgia

The Convenience of Flow Cytometry for HLA-B*5701 Screening to Prevent Abacavir Hypersensitivity Reactions

The Convenience of Flow Cytometry for HLA-B*5701 Screening to Prevent Abacavir Hypersensitivity Reactions

Cost-effectiveness analysis of HLA-B*5701 screening in preventing abacavir hypersensitivity in Spain

Purpose of the study The nucleoside reverse transcriptase inhibitor abacavir is prescribed, in combination with other drugs, for the treatment of HIV-1. Roughly 4–8% of patients receiving abacavir experience a hypersensitivity reaction (HSR), which usually appears within 6 weeks of treatment initiation. Several studies have demonstrated the association between abacavir HSR and the human leukocyte antigen (HLA)-B*5701. Therefore, systematic HLA-B*5701 screening prior to abacavir prescription enables clinicians to establish individual HSR susceptibility, and consequently increase the safety profile of HIV treatment. The objective of this study was to analyse if systematic HLAB*5701 screening to prevent abacavir HSR is a cost-effective option in the Spanish National Health System (NHS).

Incidence et motifs des arrêts prématurés de l'abacavir au cours des deux premiers mois de traitement : résultats d'une enquête hospitalière chez 628 patients

ObjectiveThe aim of this study was to determine the incidence of abacavir discontinuation within the first two months of treatment and the link with a true hypersensitivity reaction (HSR). Patients and methodsA retrospective study was made between January 1998 and January 2006 on a cohort of HIV positive patients treated by abacavir delivered by the Bordeaux Saint-André University Hospital pharmacy. ResultsSix hundred (and) twenty-eight patients were included. The reasons for non-renewal of abacavir prescription within the first three months of treatment were investigated. Early discontinuation for adverse effects was reported in 32 patients (5.1%): proved diagnosis of HSR (N=10), uncertain diagnosis of HSR (N=8), and no HSR (N=14). The decision for discontinuation was taken by physician after consultation in 76% of cases.

A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome

Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies. Whole blood samples from 84 human immunodeficiency virus (HIV) patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45 lymphocyte population. All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity. In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in <10% of the screened population.