OriginalCost-effectiveness analysis of HLA-B*5701 typing in the prevention of hypersensitivity to abacavir in HIV+ patients in SpainAnálisis coste-efectividad del tipaje HLA-B*5701 en la prevención de la hipersensibilidad al tratamiento con abacavir en pacientes VIH+ en España
Introduction
Human immunodeficiency virus type 1 (HIV-1) infection has become one of the world's greatest public health problems. However, the use of highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality associated with HIV infection.1 HAART typically includes a regimen combining nucleoside reverse transcriptase inhibitors (NRTIs) with protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).2 Abacavir is a NRTI that has shown efficacy, few drug interactions, and a favorable long-term toxicity profile.3, 4 The most important adverse effect of abacavir that limits its use in therapy is that approximately 4% to 8%5, 6, 7 of patients treated with abacavir present hypersensitivity to the drug, with an idiosyncratic systemic reaction including fever, rash, fatigue, and gastrointestinal and respiratory symptoms.6 This hypersensitivity reaction (HSR) usually appears within 6 weeks of starting treatment,6 its severity varies, and in 0.03% of patients it leads to death.6 Therefore, abacavir is contraindicated in patients who develop a HSR. Although the precise mechanisms that produce the HSR are unknown, it has been suggested that genetic, immunological, and metabolic factors are involved.8, 9 Various studies have shown a direct association between human leukocyte antigen (HLA)-B*5701 and HSR to abacavir, as patients who present the HLA-B*5701 allele have a 100-fold greater risk of experiencing HSR when exposed to abacavir.8, 10, 11, 12, 13, 14 Systematic HLA-B*5701 typing before prescribing abacavir would therefore enable clinicians to determine susceptibility to HSR, thus increasing safety in the management of HIV+ patients.
HIV is the world's main infectious cause of death and produces a substantial economic burden for society;15 thus, economic evaluations are useful to make appropriate treatment decisions based on clinical and financial grounds. Several studies have evaluated the cost-effectiveness of different HAART regimens previously.16, 17, 18 Because abacavir is one of the NRTI included in HAART regimens recommended by Spanish HIV+ treatment guidelines, the present work aims to analyze whether systematic HLA-B*5701 testing to prevent HSR in patients who are candidates for abacavir treatment is a cost-effective option for the Spanish National Health System (NHS).
Section snippets
Type of analysis
A cost-effectiveness analysis was performed to compare the healthcare costs associated with performing the HLA-B*5701 test or not in HIV+ patients before they receive antiretroviral combinations containing abacavir, with the clinical benefit in terms of HSR avoided with the test. The study was based on an analytical decision-making model in which the results were expressed in relation to the incremental cost-effectiveness ratio of screening, as cost per HSR avoided.
Pharmacoeconomic model
A simulated cohort of HIV+
Results
In the pharmacoeconomic analysis, the total direct healthcare costs included pharmacological costs, the cost of the test, and the cost of HSR management. The pharmacological costs varied according to the drug combination chosen, based on whether the patient had undergone the HLA-B*5701 test and whether the test result was positive or negative. The base case used the median cost of the test (€55) reported in a Spanish study.20 The total cost of managing each diagnosed HSR was estimated at €395,
Discussion
Several HAART regimens that do not contain abacavir are currently available on the market. Therefore, studies that provide data on the cost-effectiveness of systematic typing of the HLA-B*5701 allele to inform treatment decision-making processes are important. Systematic HLA-B*5701 typing is fundamental for preventing HSR to abacavir which, although uncommon (4% – 8%) can be serious.5, 6, 7 Genetic screening is particularly appropriate because of its negative predictive value (nearly 100%), which
Conclusion
This study shows that generalized use of HLA-B*5701 testing before administering abacavir in HIV+ patients could represent an economic saving or a limited additional cost for the Spanish NHS, which could be compensated by its benefits in terms of a lower incidence of HSR. The cost of the test varies considerably in Spain, and this factor determines whether systematic typing of the HLA-B*5701 allele is cost-effective.
Conflict of interests
Laura García-Bujalance and Isabel Pérez-Escolano work for GlaxoSmithKline, the company sponsoring this study; Óscar de la Calle, José A. Iribarren and Antonio Rivero participated in the preparation of the study as clinical experts; Diana Nieves and Max Brosa received a grant from GlaxoSmithKline to conduct the research.
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Cited by (29)
Economic analysis of pharmacogenetics testing for human leukocyte antigen-based adverse drug reactions
2023, Economic Evaluation in Genomic and Precision MedicinePharmacogenomic considerations in the treatment of HIV infection
2018, Pharmacogenomics: Challenges and Opportunities in Therapeutic ImplementationNew genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity
2015, Journal of Allergy and Clinical ImmunologyCitation Excerpt :The association between the HLA class I allele HLA-B*57:01 and abacavir hypersensitivity was first reported from Australia25 and North America26 and subsequently by a study from the United Kingdom.27 Genetic testing has been demonstrated to be cost-effective, first in the United Kingdom27 and subsequently in other countries.28-30 Furthermore, preprescription testing for HLA-B*57:01 reduced the frequency of hypersensitivity in Australia,31 the United Kingdom,32 and France,33 showing that genetic testing can have a powerful influence in reducing the burden associated with serious ADRs.
Drug Allergy. Generic Protocol
2014, Middleton's Allergy: Principles and Practice: Eighth EditionSevere abacavir hypersensitivity reaction in a patient with human immunodeficiency virus infection: a case report
2022, Journal of Medical Case ReportsCost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review
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