The clearest result in all of pharmacogenomics: test before the first dose, do not prescribe if positive, and a reaction that used to be feared largely stopped happening. It is also the same allele that makes some people control HIV unusually well.
Abacavir is an antiretroviral used to treat HIV. In a small minority of people it causes a hypersensitivity reaction — fever, rash, gut and breathing symptoms — that worsens with each dose and can be fatal on re-exposure.
That reaction is almost entirely confined to people carrying one HLA allele.
Pharmacogenomics is usually a story of modest effects and hedged guidance. This one is not. The association between HLA-B*57:01 and abacavir hypersensitivity is strong enough, and specific enough, that pre-treatment screening became standard practice — and the reaction it prevents became rare.
CPIC published guidance on HLA-B genotype and abacavir in 2012 and reviewed it again in 2014, concluding that nothing in the intervening literature would change the recommendation. A guideline that survives its own review unchanged is unusual, and it is a reasonable measure of how settled this is.
rs2395029 sits in the HLA region and tags HLA-B*57:01. Our catalogue records it under a completely different trait: HIV-1 control.
That is not a filing error. The same allele is one of the strongest known genetic factors in people who control HIV without treatment — so-called elite controllers. HLA-B*57:01 presents viral peptides to the immune system unusually effectively.
So one allele, in one gene, in the context of one virus: it makes the immune response to HIV better, and the reaction to a drug used against HIV worse. Both effects come from the same property — how forcefully this molecule presents a peptide to T cells. It presents a viral peptide well, and it presents an abacavir-modified peptide as though that were foreign too.
It is the cleanest illustration on this site that a variant is not good or bad. It does something, and what that is worth depends on the situation.
HLA-B*57:01 is typed in a clinical laboratory before the first dose. It is a yes-or-no result, ordered by the prescriber, and it changes a decision: if positive, abacavir is not used and another drug is chosen.
This is not a test to run on a raw data file. A SNP used as a proxy for an HLA allele tags it well in some populations and poorly in others, and here the cost of being wrong runs in both directions — a false negative exposes somebody to a dangerous reaction, and a false positive removes a useful drug from their options for no reason.
See drug-induced SJS/TEN for the same logic applied to allopurinol and carbamazepine, and CCR5-delta32 for a different piece of HIV genetics entirely.
Guideline. CPIC Guidelines for HLA-B Genotype and Abacavir Dosing were originally published in April 2012; the 2014 update reviewed subsequent literature and concluded that none of the evidence would change the therapeutic recommendations, so the original publication remains clinically current. Supplementary material and electronic health record implementation resources were updated.
Position listed here. rs2395029, in the MHC, used as a tag for HLA-B*57:01. It is recorded in our catalogue under HIV-1 control, which is the trait the source study reported. Tagging accuracy is population-dependent and this page does not treat the SNP as equivalent to an allele call.
Mechanism. Abacavir binds non-covalently within the peptide-binding groove of HLA-B*57:01, altering the repertoire of self-peptides presented and producing a T-cell response against what is effectively an altered self. The same allele's presentation properties underlie its well-documented association with spontaneous control of HIV-1 viraemia — the two phenotypes share a mechanism rather than merely a locus.
Clinical use. Pre-treatment HLA-B*57:01 screening is standard of care where abacavir is prescribed. A positive result contraindicates abacavir. Testing is performed by clinical HLA typing, not inferred from array genotypes.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Abacavir Hypersensitivity (HLA-B*57:01) comes down to these specific, well-studied positions — not a diagnosis.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| HLA-B | Abacavir | HLA-B*57:01 carriage is strongly associated with abacavir hypersensitivity, a reaction that can be fatal on re-exposure. CPIC issued guidance in 2012 and confirmed in its 2014 update that the recommendation was unchanged: screen before the first dose and do not prescribe abacavir to a carrier. This is a pre-prescription safety test performed by clinical HLA typing, and it is the example most often given of pharmacogenomics changing practice — the reaction became uncommon where screening was adopted. (CPIC Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update (Clin Pharmacol Ther 2014, PMID 24561393).) |
Because both come from the same property. HLA-B*57:01 presents peptides to T cells unusually forcefully. Presenting a viral peptide well is why carriers are over-represented among people who control HIV without treatment; presenting an abacavir-altered self-peptide as though it were foreign is why they react to the drug. The allele is not good or bad — it does something, and what that is worth depends on the situation.
No, and here the cost of being wrong runs both ways. A SNP used as a proxy for an HLA allele tags it well in some populations and poorly in others. A false negative would expose somebody to a dangerous reaction; a false positive would remove a useful drug from their options for no reason. It is typed in a clinical laboratory before the first dose.
Because it actually changed practice. The association is strong and specific, the test is a yes or no, and a positive result changes the prescription. The guideline was reviewed two years after publication and left unchanged, which is a fair measure of how settled it is.
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