Analysis of FDA Guidance Document on Management of Donors at Increased Risk for HIV-1 Group O Infection

"Guidance for Industry: Recommendations for Management of Donors at Increased Risk for Human Immunodeficiency Virus Type 1 (HIV-1) Group O Infection,” which was published by the Food and Drug Administration Aug. 31, provides recommendations for blood and plasma establishments that includes an extended list of African countries where HIV-1 group O is endemic; the method for reporting to FDA that donor questioning has been replaced by a donor screening test with the appropriate “Intended Use” claim in the package insert; and a method for re-entry of donors deferred on the basis of a positive response to HIV-1 group O risk questions.

Intended for immediate implementation, this guidance supersedes the Dec. 11, 1996 memorandum “Interim Recommendations for Deferral of Donors at Increased Risk for HIV-1 Group O Infection,” which contained interim measures — donor screening questions — to reduce the risk of HIV-1 group O transmission by blood and blood products pending licensure of test kits capable of detecting HIV-1 group O virus antibodies. FDA previously issued a guidance document for immediate implementation – December 2007 – to replace the 1996 interim measures but withdrew the guidance a few days later.

The first donor screening test that is specifically labeled in the “Intended Use” section of the package insert as sensitive for detection of HIV-1 group O antibodies was licensed by FDA in 2003. A listing of FDA-licensed donor screening test kits can be viewed on the FDA Web site. It should be noted that as of this writing only one donor screening test for HIV-1 group O antibodies with the relevant claim has been licensed. Other assays for HIV-1 group O detection are under development and, if approved by FDA, may be used when available for screening donors as described in their package inserts.

Revised Questions to Identify Donors at Increased Risk of HIV-1 Group O Infections

The guidance document provides a revised list of countries that should be included in the donor history screening process for identifying donors at increased risk for HIV-1 group O infection. This list includes five new countries where the virus is endemic — Benin, Kenya, Senegal, Togo and Zambia. (Benin and Kenya were not identified in the guidance that was released and then withdrawn in December 2007.) In addition, FDA clarified that the Democratic Republic of the Congo — formerly Zaire — is not considered part of the Congo and has not identified any cases of HIV-1 group O infections thus far; therefore, it is not a cause for deferral. A map of Africa identifying the endemic countries, as well as a table comparing the current listing of the countries to those identified in the 1996 guidance, are included.

The time period to be covered by the questions – “since 1977” – remains unchanged. If a potential donor responds affirmatively to any of the questions, an indefinite deferral is recommended. See below for recommendations on re-entry.

  1. Were you born in or have you lived in any of the following countries since 1977: Cameroon, Benin, Central African Republic, Chad, Congo, Equatorial Guinea, Kenya, Gabon, Niger, Nigeria, Senegal, Togo, or Zambia? If so, when?
  2. If you have traveled to any of those countries since 1977, did you receive a blood transfusion or any medical treatment with a product made from blood? If so, when?
  3. Have you had sexual contact with anyone who was born in or lived in these countries since 1977? If so, when?

FDA added a note to clarify that establishments that have implemented the AABB full-length donor history questionnaire, or DHQ, and accompanying materials should question donors concerning possible exposure to HIV-1 group O virus using the capture question approach developed for this protocol. The AABB Donor History Task Force submitted updated blood donor history questionnaire materials to FDA in May 2008 following issuance of the 2007 guidance document that was withdrawn. The updated materials include all five nations that have been added to the list of endemic countries. FDA has not released a guidance document recognizing the updated materials and they have not been posted on the AABB Web site. In the interim, establishments can update standard operating procedures and flowcharts corresponding to the relevant questions (46 and 47) to reflect the addition of the five countries.

The HPC-DHQ developed by the DHQ Cellular Therapies Task Force to screen allogeneic hematopoietic progenitor cell donors for communicable disease risk factors does not go through a review process with FDA and has been updated to include the additional countries of risk that were identified in the guidance document.

Discontinuation of the Questions that Address HIV-1 Group O Risk

Screening questions to identify donors at increased risk for HIV-1 group O infection may be discontinued if the establishment has implemented a licensed anti-HIV-1/2 test for donor screening that is specifically labeled in the “Intended Use” section of the package insert as sensitive for detection of HIV-1 group O antibodies. At the time of this guidance document release, only the Genetic Systems HIV-1/HIV-2 plus O EIA test is licensed with the appropriate labeling claim. Other approved HIV tests for donor screening, including nucleic acid tests on the FDA Web page (see above), do not currently have the appropriate labeling claim.

Establishments that are required to submit annual reports to FDA — those with biologics licenses — should report the discontinuation of questions due to implementation of the appropriate donor screening test as a minor change (21 CFR 601.12(d)).

Re-entry of Donors Deferred on the Basis of an Affirmative Response to HIV-1 Group O Risk Questions

The recommendations on re-entry of donors deferred due to affirmative responses to the donor history questions are the most significant difference between this guidance document and the one that was released and withdrawn in December 2007. The current recommendations allow for re-entry based on EIA testing performed on a donation versus the 2007 recommendation that the testing be performed on a follow-up sample and that an individual donation NAT test also be performed, even though NAT tests available for donor screening do not have appropriate labeling claims, i.e., sensitive for detection of HIV-1 group O. What is not included in the current guidance document recommendations is a pathway to the re-entry of donors who test repeatedly reactive on the approved HIV-1 group O screening test.

The new guidance states: A donor who was deferred because of a previous or current affirmative response to one or more of the questions in the donor history questionnaire related to HIV-1 group O risk may be eligible for re-entry after a waiting period of at least one year following the date of the donor’s last potential exposure to HIV-1 group O. The donor may be re-entered if:

  1. A current donation from the donor is tested and found non-reactive using an anti-HIV-1/2 screening test that is specifically labeled in the “Intended Use” section of the package insert as sensitive for detection of HIV-1 group O antibodies, and
  2. The donor meets all other donor eligibility criteria. (FDA added a footnote reminding establishments that the HIV-1 group O endemic countries in Africa also are endemic for malaria.)