On Mar. 4, 1985, the Red Cross Blood Services began testing all newly donated blood with the first HIV detection test immediately after its U.S. Food and Drug Administration (FDA) approval one day earlier.

Many improvements in testing have occurred, including the detection of a second HIV agent (HIV-2 in 1992). The test used for blood donor screening is the GS (Genetic Systems’ distributed by Ortho) HIV-1/HIV-2 PLUS O EIA for the simultaneous qualitative detection of anti-HIV 1 (groups M and O) and/or HIV-2 in human serum or plasma. A duplex NAT was introduced for HIV/HCV RNA detection in September 1999 and updated to include the detection of HBV DNA in June 2009 (see above) and HIV-2 RNA detection in July 2020.

Donors who test antibody reactive are further evaluated by additional tests to confirm the presence of HIV antibodies and to differentiate HIV-1 from HIV-2 antibodies. Such tests have included an HIV western blot, an HIV-2 enzyme-linked immunoassay (EIA), and an HIV-1 and HIV-2 rapid test for viral differentiation (all FDA licensed), but now with the elimination of the western blot and HIV-2 EIA, only the rapid test (Genetic Systems’ GEENIUS) is used. Donors who test anti-HIV-1/HIV-2 and HIV NAT reactive are not further tested.

Currently only the rapid test is performed on HIV-1/HIV-2 antibody-reactive donations that test NAT negative to confirm antibody reactivity and differentiate HIV-1 from HIV-2 antibodies. Donors testing falsely positive by either antibody or HIV NAT may be reentered. The last published per-unit risk of HIV infection through blood transfusion (chance of releasing an infectious blood component) including data through 2019 is less than 1 per 2 million units screened but continues to decrease. NAT closes the window period between infection and antibody detection for those infected with HIV by about 2 weeks. This leaves an approximate period of 7 to 10 days when an infected donor may not be detected by blood donation screening.

Since the first implementation of HIV NAT in 1999, only 5 transfusion-transmitted HIV infections have been documented (from 6 infected donors). The frequency of detecting HIV-1 in a blood donor is about 1 per 33,000 donations screened. However, detecting HIV-2 in a blood donor is extremely rare at 1 per 57 million donations, with only 5 such infected donors ever identified since HIV-2 screening began in 1992.