A colleague in Massachusetts reports that her institution is considering changing their current HIV deferral policy of permanently deferring anti-HIV-1 EIA reactive, but Western blot negative donors, to a policy that allows for donor re-entry. The proposed reentry protocol is identical to the one shown in figure 2 on page 17 of the FDA Memo of April 23, 1992 entitled 'Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood Products' (PDF).

She is curious to learn if other donor centers are re-entering donors who are HIV EIA reactive, Western Blot negative, and if so, what reentry protocol do they use. In addition, she wonders how many donor centers just permanently defer these donors, and not bother with a reentry protocol.

The following comments have been received.

ADDENDA Jan. 23, 2004

1. Ronald E. Domen, MD at Milton S. Hershey Medical Center, Penn State University College of Medicine offers the following comments: "We have used the FDA's re-entry algorithm and are unaware that any other approach would be acceptable to the FDA. We are having a problem finding a testing lab that will perform the necessary whole viral lysate HIV testing for re-entry. We also have identified a few donors who have 'uninterpretable' Western blot tests because of possible 'interfering substances.' We have been unable to get guidance on how to re-enter these donors. Also, now that NAT is also routine, there is no guidance on how NAT should be used or interpreted in the re-entry protocol. Until these questions get resolved we have a number of donors who cannot donate, and we may be forced to discontinue any re-entry and permanently defer all donors who have an initially reactive HIV EIA. The FDA's 1992 recommendations are outdated and in dire need of being revised in light of today's testing."

ADDENDA Jan. 30, 2004

2. A colleague in California reports that his blood center is able to successfully complete HIV re-entries routinely by precisely following the cited FDA guidance. In their experience, an estimated 25% of donors fail reentry. The Californian cautions that following the FDA guidance strictly as written is an absolute requirement, though, and the reentry algorithm is complicated (and perhaps confusing) enough that many may choose to not risk the possibility of making a mistake trying to follow it. The concern, of course, is that a blood donation by a donor who has been re-entered incorrectly would be an FDA reportable "error" and would result in a formal recall of units shipped for transfusion; the Californian reports knowing that this HAS happened. He adds: "So ... true, it’s simpler not to do it. But if it is actually permitted that you can do something (relatively effortless) to possibly save an otherwise (permanently) lost donor, some would (and do) do it. Like Dr. Domen, we too look forward to the expected new FDA guidance for HIV (and HCV) reentry now that HIV/HCV NAT is licensed. And we've also experienced some difficulty maintaining access to a whole viral lysate based anti-HIV-1 EIA (required for reentry according to the current guidance). We recently had to discover a new reference laboratory that offered this testing (LABCORP, San Diego, CA), since our previous source (BIO-RAD, Redmond, WA) discontinued it."

ADDENDA July 11, 2007

3. A transfusion medicine physician reports that his Southern California Community Blood Bank has never had an SOP for re-entry of donors who were reactive in a screening test for HIV antibodies, but were unconfirmed by Western blotting or IFA. He wants to institute a re-entry protocol because they defer about one or two donors a month due to unconfirmed reactive HIV antibody screening. His understanding is that as per the April 23, 1992 FDA Revised Recommendations (summarized in figure 2, page 17) if a donor is:

1. RR by EIA but negative by licensed IFA, or Western Blot (and NAT of course) you wait 6 months and then ...
2. Do the following:
   1. Repeat the EIA by the same method (or a licensed substitute as per page 13 if the original test is not available anymore),
   2. a "whole viral lysate" HIV EIA
   3. Licensed HIV-1 Western blot or IFA
   4. HIV-2 EIA

Although the above protocol seems 'simple enough', he is unsure where to acquire a "whole viral lysate" HIV-1 EIA. He wonders if the FDA has updated this process beyond their draft guidance from July 2005 which is for "comment purposes only". He hopes to see any comments other colleagues might share, especially if they have an active re-entry program. He also would like to know if anyone has re-entered a donor with a false positive HIV-1 P24 antigen test because this issue is not addressed in the 1992 recommendation.

ADDENDA July 27, 2007

4. According to the Director of Special Donor and Community Health Services at a blood center in New York, the response form Southern California regarding reentry of HIV RR/WB or IFA negative donors (posting #3 on July 11, 2007) defines the problem exactly. The New Yorker points out that there is no HIV whole viral lysate tests currently available and that reentry of donors with the aforementioned test results was extremely labor intensive, even when whole viral lysate tests were available. She notes that FDA has had a draft guidance for 3 years that could simplify the process and also permit re-entering p24 false positive donors. She wishes that the agency would finalize the guidance so that we could all move forward with reentry.

ADDENDA Aug. 7, 2007

5. According to a blood banker in Colorado, (in contrast to comments by the Director of Special Donor and Community Health Services at a blood center in New York - see posting of July 27, 2007), there is an FDA licensed whole viral lysate test available, "Human Immunodeficiency Virus Type 1 (Whole Viral Lysate and E. coli Recombinant Antigen) Genetic Systems (tm) rLAV EIA". Manufacturer: Bio-Rad Laboratories Blood Virus Division Redmond, WA (see FDA/CBER Product Approval Information - Licensing Action).

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