Context: Persons at risk of human immunodeficiency virus 1 (HIV-1) infection, have been classified incorrectly as HIV infected because of Western blot results, but the frequency of false-positive Western blot results is unknown.
Objectives: To determine the frequency of false-positive HIV-1 Western blot results in US blood donors and to make projections to other screened populations. Secondarily, to validate an algorithm for evaluating possible false-positive cases.
Design: A retrospective cohort study of HIV-1 enzyme immunoassay (EIA) and Western blot results from large blood donor screening programs in which donors with suspected false-positive Western blot results underwent HIV-1 RNA polymerase chain reaction (PCR) testing and follow-up HIV-1 serology.
Setting: Five US blood centers participating in the Retrovirus Epidemiology Donor Study.
Participants: More than 5 million allogeneic and autologous blood donors who successfully donated blood at 1 of the 5 participating centers from 1991 through 1995.
Main outcome measures: Rate of false positivity by Western blot and true HIV-1 infection status as determined by HIV-1 RNA PCR and by serologic follow-up of blood donors more than 5 weeks after donation.
Results: Of 421 donors who were positive for HIV-1 by Western blot, 39 (9.3%) met the criteria of possible false positivity because they lacked reactivity to p31. Of these, 20 (51.3%) were proven by PCR not to be infected with HIV-1. The false-positive prevalence was 4.8% of Western blot-positive donors and 0.0004% (1 in 251000) of all donors (95% confidence interval, 1 in 173000 to 1 in 379000 donors).
Conclusions: A false diagnosis of HIV-1 infection can result from the combination of EIA and Western blot testing in blood donor and other HIV-1 screening programs. Individuals with a positive Western blot result lacking the p31 band should be counseled that, although they may be HIV infected, there is uncertainty about this conclusion. These individuals should be further evaluated by RNA PCR testing (if feasible) and HIV serologic analysis on a follow-up sample.