Vaccine-induced antibodies to envelope proteins frequently cause HIV seroconversion in uninfected recipients of HIV vaccine candidates and may thus have an impact on the vaccinee's ability to donate blood or acquire a life insurance policy.To determine the occurrence of positive test results when commonly used HIV immunoassays are used to screen sera of HIV-uninfected volunteers who received an adjuvanted HIV-1 vaccine candidate containing HIV-1 antigens p24, reverse transcriptase, Nef and p17.Sera of 50 subjects who received this polyprotein vaccine in a single center in Belgium were tested with 6 HIV screening assays and 1 confirmation test. All samples were drawn one year after the administration of the first of two vaccine doses given with one month interval.Forty-five (90%) sera showed a positive test result in at least one of the 7 HIV tests used. The positivity rates were 88% in the Elecsys HIV Combi assay, 74% in the ADVIA Centaur EHIV and 48% in the PRISM HIV O Plus assay.Interpretation of HIV test results is becoming increasingly complex with the growing number of volunteers participating in prophylactic HIV vaccine trials worldwide and the rising number of viral antigens included in these vaccine candidates. The results of this study in recipients of a highly immunogenic adjuvanted polyprotein HIV vaccine candidate devoid of envelope proteins, illustrate the increasing need for approaches that can discriminate HIV infection-induced antibodies from those elicited by a vaccine.