HLA-B*57:01-guided abacavir prescribing is the clearest preventive paradigm from HLA associations

Human leukocyte antigen (HLA) polymorphisms are central to anti-infective pharmacogenetics and to inter-individual variability in infection outcomes and vaccine responses, but clinical relevance depends on whether an association changes treatment or prevention decisions. This narrative review is organized around two complementary pillars: first, severe, typically T cell–mediated adverse drug reactions to anti-infective agents, where HLA can support prevention when genetic effect, phenotype precision, and therapeutic alternatives converge; and second, selected, replicated HLA-region associations with infection outcomes or vaccine immunogenicity, where biological effects may be robust yet individual-level clinical translation is often limited. Within the adverse drug reaction pillar, the clearest preventive paradigm remains HLA-B*57:01-guided abacavir prescribing, with additional high-signal examples including dapsone hypersensitivity and flucloxacillin-induced liver injury that illustrate how large effect sizes do not always justify routine screening. Within the infection and vaccine pillar, HIV, HCV, and hepatitis B vaccine response provide the strongest evidence that HLA shapes clinically relevant host-response heterogeneity. Across both domains, the key pharmacological distinction is between mechanistically persuasive associations and those that are sufficiently robust, transportable, and decision-relevant to change practice.