Among Australians treated for advanced HIV disease, a suboptimal virological response was associated with allele 2 at interleukin 1 alpha (IL1A)−889 and IL1A+4845. This is confirmed and investigated using patients from AIDS Clinical Trials Group study 384 (n = 532). Among non-African–American patients with CD4 T-cell count of ≤100 cells/μl at baseline, IL1A+4845*TT was associated with poor virological outcome (P = 0.03). Differences were smaller with higher baseline CD4 T-cell counts. IL1A−889 and IL1A+4845 were not in linkage disequilibrium in African–American patients, and IL1A+4845*T did not affect outcome.