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Objective: To evaluate whether HLA-B35 influences progression to AIDS in HIV-seropositive subjects with haemophilia.Design: Retrospective (before 1985) and prospective (after 1985) follow-up of a group of French haemophiliacs.Methods: We studied 144 seropositive patients with moderate or severe haemophilia A or B or von Willebrand's disease. Enzyme-linked immunosorbent assay was used to screen patient sera for total HIV antigen and core p24 antigen antibodies. All patients were typed for HLA A, B and C antigens in the same laboratory. Time of seroconversion was estimated to be the mid-point between the last seronegative test and the first seropositive test. AIDS-free survival curves were constructed using the Kaplan—Meier estimate and differences in survival analysed using the Mantel—Cox test. The Cox proportional hazards model was used to adjust for confounding variables.Results: Median follow-up after seroconversion was 8.7 years (range, 3.5–10.7 years). By the end of the study, six HLA-B35-positive patients and 12 HLA-B35-negative patients had progressed to AIDS. Individuals with HLA-B35 showed a significantly faster rate of progression to AIDS over the follow-up period than HLA-B35-negative individuals (hazard ratio, 2.72; P = 0.037). After adjusting for type and severity of haemophilia, CD4 cell count at first seropositive test, age at seroconversion, and zidovudine treatment before AIDS, the hazard ratio was 2.74 (P = 0.045).Conclusion: HLA-B35 is a risk factor for more rapid progression to AIDS in subjects with haemophilia.