A blood banking colleague in the Northeastern USA wants to know what is the current required lookback procedure for when a donor tests 'confirmed positive' for HIV-1 p24 antigen. In a recent FDA inspection of her donor center it was noted that a lookback procedure had not been performed for previous donations of a donor who had an isolated positive test result (in April '02) for HIV-1 p24 antigen. The donor was negative for HIV 1/2 antibody as well as for HIV NAT. The closest previous donation had been three years prior, at which time all disease markers were negative. The inquiring blood banker reports that the only document they could find that addresses lookback for a HIV-1 p24 antigen positive blood donation is an 8/8/95 CBER "Recommendations for Donor Screening with a Licensed Test for HIV-1 Antigen". This document appears to require a blood center to go back three months prior to a repeatably reactive donation to "notify consignees of the results of a positive test on the donor's current sample". Is this interpretation correct, or do other rules/regulations need to be considered?

The following responses were received.

1. An internationally acknowledged expert in blood donor testing for HIV infection reports that a negative HIV RNA by current NAT assays is unequivocal evidence that antibody-negative HIV p24 antigen reactivity in a donor, "confirmed by neutralization", represents a false-positive result. Such false-positive neutralization results have been seen prior to and during routine donor screening, and are much more common than true HIV p24 antigen positive/antibody negative units. According to the expert, FDA clearly agrees with this conclusion given their allowance of discontinuing HIV p24 antigen screening if licensed NAT for HIV is in place.

ADDENDUM Aug. 16

2. A second expert agrees with the opinion expressed by the first expert in reply #1 above. According to the second expert, since the implementation of p24 Ag screening (March, 1996), her organization has observed false-positive "confirmed by neutralization" samples that are HIV antibody negative and HIV RNA negative. All such samples have been tested for HIV RNA by PCR and most recently since the implementation of TMA screening, by both PCR and TMA, and have been found negative; this is supplemented by the fact that if the initial neutralization test is repeated, the confirmed positive result cannot be reproduced; in addition, these donors demonstrate no evidence of HIV infection by follow up sampling (negative by HIV antibody, antigen and RNA).

Please submit comments to the e-Network Forum.

Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator