ContextEvaluating trends in blood donor infectious disease rates is essential for monitoring blood supply safety and donor screening effectiveness. ObjectiveTo determine changes over time in blood donor population infection rates of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV).Design Cross-sectional survey data from the National Heart, Lung, and Blood Institutesponsored Retrovirus Epidemiology Donor Study. Setting Five blood centers in different regions of the United StatesParticipants A total of 1.9 million volunteer blood donors with 1 or more nonautologous donations from January 1991 to December 1996. Main Outcome MeasuresChanges in rates of HIV, HTLV, HCV, and HBV infections were evaluated by comparing yearly prevalence estimates (per 100 000 donations) for first-time allogeneic donors and period-specific incidence rates (IRs) (per 100000 person-years) for repeat allogeneic donors between 1991 and 1996 (for HCV, from about March 1992 to June 1996). ResultsPrevalence of HIV decreased in first-time donors from 0.030% to 0.015% (P=.006) and HCV prevalence decreased from 0.63% to 0.40% (PϽ.001).Trends were not statistically significant for the proportion of first-time donors with hepatitis B surface antigen (HBsAg) or HTLV.For repeat donors, IRs did not change significantly, indicating a stable but low level of seroconversion.The overall IRs (95% confidence intervals) per 100 000 person-years were 2.92 (2.26-3.70)for HIV, 1.59 (1.12-2.19)for HTLV, 3.25 (2.36-4.36)for HCV, and an estimated 10. 43 (7.99-13.37)for HBV (based on an HBsAg rate of 2.66 [2.04-3.41]with presumed false-positive results considered negative).The HBV IR estimate with presumed false-positive results considered positive (for comparability to previous analyses) was 17.83 (14.60-21.56). ConclusionThe decrease in HIV and HCV prevalence rates, combined with the previously documented lower rates of infection in first-time donors compared with the general population, suggests the continued benefit of behavioral risk factor screening.