Clinical area · HLA

In some drug reactions, dose adjustment does not help.

HLA genes can lead the immune system to treat a drug as a threat. The result can be severe skin reactions such as Stevens-Johnson syndrome and TEN. This risk can be seen before the drug is started.

Prepared by the BIODECODE science team · Last updated: October 2026 · Based on CPIC, DPWG, FDA and peer-reviewed publications

In brief

  • HLA genes are the immune system's "identity check". Certain HLA variants make specific drugs look like a threat to the immune system.
  • These reactions are not dose-related; even a low dose can trigger them. The answer is therefore not dose adjustment, but never starting the drug in a person at risk.
  • The test is done once and stays valid for life. Its clinical value is established for abacavir, carbamazepine, oxcarbazepine, phenytoin, allopurinol and dapsone.

Key concepts

What is HLA?

Molecules on the surface of cells that show the immune system "what is inside this cell". They are also the genes examined for tissue matching in organ transplantation.

Risk allele

A specific form of a gene that markedly increases the risk of a severe reaction to a particular drug. HLA-B*57:01, for example, is the risk allele for abacavir.

SJS and TEN

Stevens-Johnson syndrome and toxic epidermal necrolysis: life-threatening reactions in which the skin and mucous membranes peel extensively and intensive care may be needed. TEN is the more extensive and severe form.

Hypersensitivity syndrome

An immune reaction with fever, rash, gastrointestinal and respiratory symptoms that can worsen if the drug is not stopped. With abacavir it typically appears in the first weeks of treatment.

How does the reaction develop?

  1. The drug binds to the HLA molecule

    In a person carrying the risk allele, the drug, or small protein fragments presented with it, fits into the structure of the HLA molecule.

  2. The immune system mistakes it for a foreign body

    T cells recognise this newly shaped HLA complex as a dangerous intruder and raise the alarm.

  3. The body attacks its own tissue

    The immune response targets the skin, mucous membranes and internal organs. The reaction usually appears in the first weeks of treatment.

What does the result mean?

Test resultMeaningGeneral guideline recommendation
Risk allele positiveThe risk of a severe reaction to the related drug is markedly increased.If the drug is about to be started, it is not recommended; a suitable alternative is chosen.
Risk allele negativeRisk linked to this allele is largely excluded.The drug can be used; routine clinical monitoring continues.

For some drugs such as carbamazepine, a medicine used without problems for months may not always need to be stopped. That decision belongs to the physician.

Who is it relevant for?

  • Patients about to start abacavir for HIV
  • Patients about to start carbamazepine, oxcarbazepine or phenytoin for epilepsy, trigeminal neuralgia or bipolar disorder
  • Patients about to start allopurinol for gout or high uric acid
  • Patients for whom dapsone is planned
  • People who have had a severe skin reaction to a drug in the past

Your physician decides whether the test is right for you.

Evidence

  • ~30%

    Reported mortality in TEN

    Systematic review: Mahar et al., Burns 2014
  • 2.7% → 0%

    Immunologically confirmed abacavir hypersensitivity after HLA-B*57:01 screening; negative predictive value 100%

    PREDICT-1 · Mallal et al., NEJM 2008
  • ~10 → 0

    Expected SJS/TEN cases among 4,877 patients screened for HLA-B*15:02

    Chen et al., NEJM 2011
  • 26% / 3.8%

    Probability of carbamazepine hypersensitivity in Northern Europeans with and without HLA-A*31:01

    McCormack et al., NEJM 2011

Related genes and drugs

GeneRoleRelated drugsSource
HLA-B*57:01A form of HLA-B, one of the immune system's identity-check genesAbacavirCPIC A
HLA-B*15:02The form of HLA-B linked to aromatic antiepilepticsCarbamazepine, oxcarbazepine, phenytoinCPIC A
HLA-A*31:01The form of HLA-A linked to carbamazepineCarbamazepineCPIC A
HLA-B*58:01The form of HLA-B linked to allopurinolAllopurinolCPIC A
HLA-B*13:01The form of HLA-B linked to dapsoneDapsoneDPWG / literature

What you will see in the BIODECODE report

  • 11 loci

    HLA-A, B, C, DPA1, DPB1, DQA1, DQB1, DRB1 and DRB3/4/5 are sequenced in one panel.

  • Direct typing

    Class I risk alleles are not inferred from proxy SNPs; they are typed from sequencing reads.

  • Multiple solutions

    The result rests on a comparison of several typing solutions.

  • Drug mapping

    Every risk allele is shown in the report together with its related drugs.

Sample report (PDF)

Good to know

  • Not every hypersensitivity reaction is HLA-related. A negative result does not replace clinical monitoring.
  • The test only informs about the risk alleles examined; it cannot predict a reaction arising from an unknown mechanism.
  • Risk-allele frequencies vary by ancestry. Individual testing is therefore recommended over ancestry-based guessing.

Frequently asked questions

Is HLA testing done only once?

Yes. HLA genotype does not change over a lifetime; the result remains valid for medicines prescribed in the future.

Is testing only needed for people of Asian ancestry?

Risk-allele frequencies vary by ancestry and some guidelines limit testing to certain ancestries. Yet studies have shown, for example, that a share of HLA-B*15:02 carriers are not of Asian ancestry. In genetically diverse populations, ancestry-based guessing is unreliable.

Does a negative result mean no reaction will ever occur?

No. A negative result largely excludes risk linked to that HLA allele, but not every hypersensitivity reaction is HLA-related. Clinical monitoring is always needed.

I have used this drug before without problems. Do I still need the test?

Risk is assessed differently for a drug used without problems for a long time. Your result may still be valuable for other drugs prescribed in the future. The decision is your physician's.

References

  1. Mallal S et al. HLA-B*5701 screening for hypersensitivity to abacavir (PREDICT-1). N Engl J Med. 2008.
  2. Chen P et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011.
  3. McCormack M et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011.
  4. Zhang FR et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013.
  5. Mahar PD et al. Mortality in toxic epidermal necrolysis: a systematic review. Burns. 2014.
  6. CPIC guidelines: HLA-B and abacavir; HLA-B, HLA-A and carbamazepine/oxcarbazepine; HLA-B and allopurinol.

This page is for information only; diagnosis and treatment decisions belong to your physician. Never stop or change a medicine on your own.

All clinical areas