Human Immunodeficiency Virus (HIV) and Our Industry: FDA’s Upcoming Guidance
Thanks for joining! Today we’re going to dive into the Food and Drug Administration’s (FDA) guidance, “Recommendations to Reduce the Risk of Transmission of Human Immunodeficiency Virus (HIV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)” which is currently in its comment period, and has yet to be implemented. This guidance updates information regarding HIV risk and will supersede the “Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue Based Products (HCT/Ps), Guidance for Industry,” dated August 2007), once implemented.
The revised recommendations are for:
1. Donor screening that includes reducing certain time-based risk factors and conditions.
2. Assessing every HCT/P donor for HIV risk, using the same individual risk-based questions regardless of sex or gender.
3. Use of an FDA-licensed donor screening test that includes detection of anti-HIV-1 group O, and removing the recommendation to screen HCT/P donors for HIV-1 group O risk.
HIV is a retrovirus consisting of two types, HIV type 1 (HIV-1) which accounts for the majority of global HIV infections, and HIV type 2 (HIV-2). HIV-1 and HIV-2 share many similarities including their basic gene arrangement, modes of transmission, intracellular replication pathways, and clinical consequences: both result in AIDS (if untreated). However, HIV-2 is characterized by lower transmissibility and reduced likelihood of progression to AIDS 1 . Per the FDA, HIV-1 and HIV-2 are identified as relevant communicable disease agents or diseases (RCDADs) where HIV-1 contains different groups (i.e., groups M, N, and O), group O is common in Africa and a few cases outside of Africa. HIV-2 occurs primarily in West Africa, but an increasing number of cases have been recognized in the U.S., Europe, and India.
The guidance provides the thought for blood donors and considerations to increase the donor pool by using data from successful models used by the United Kingdom and Canada - a new approach for questions regarding men having sex with men (MSM). This approach utilizes individual risk factors based on surveillance, epidemiology, and risk assessments that demonstrate new or multiple sexual partners, and for those with new or multiple partners, anal sex, are the most significant risk factors that increase the likelihood of HIV infection. FDA updated their stance and eliminated the blood donor screening questions specific to MSM and women who had sex with MSM and assessed blood donor eligibility using the same individual risk-based questions relevant to HIV risk for every donor, regardless of sex or gender.
For HCT/Ps, FDA is moving with the recommendation of the three (3) month risk period, in addition to using approved HIV tests for testing HCT/P donors based on their review of the available science, adequacy of available test methods, studies used to evaluate risk behaviors, and experiences with updated blood donor screening questions.
Screening:
Relevant medical records must be reviewed that include a report of the physical examination of a living donor, and ask questions about the donor’s medical history and relevant conditions and behavioral risks including risk factors for RCDADs.
Addition of appropriate screening measures to identify the use of antiretroviral drugs used to treat or prevent HIV infection (these affect test results by reducing the HIV viral load to undetectable levels but do not fully eliminate the virus from the body).
Ineligible donors:
1. Those who are taking medications to treat or prevent HIV infection (e.g., antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP)).
2. Persons who have ever had a positive or reactive screening test for HIV.
3. Persons who have engaged in non-prescription injection drug use in the preceding 3 months, including intravenous, intramuscular, or subcutaneous injections.
4. Persons who have had sex (unless specified as “anal sex”, the term “sex” or “sexual contact” refers to vaginal, anal, or oral sex, regardless of whether a condom or other protection is used) in exchange for money or drugs or other payment 2 in the preceding 3 months.
5. Persons who have had sexual contact in the preceding 3 months with any individual who has ever had a positive test for HIV infection.
6. Persons who have had sexual contact in the preceding 3 months with any individual who has exchanged sex for money, drugs or other payment. If there is any uncertainty about when their sexual partner exchanged sex for money, drugs or other payment, the person is ineligible for 3 months.
7. Persons who have had sexual contact in the preceding 3 months with any individual who has engaged in non-prescription injection drug use. If there is any uncertainty about when their sexual partner engaged in non-prescription injection drug use, the person is ineligible for 3 months.
8. Persons who have had a new sexual partner (for the purposes of this guidance, the following examples would be considered having sex with a new partner: having sex with someone for the first time; or having had sex with someone in a relationship that ended in the past and having sex again with that person in the last 3 months.) in the preceding 3 months and have had anal sex in the preceding three months.
9. Persons who have had more than one sexual partner in the preceding 3 months and have had anal sex in the preceding three months.
10. Persons who have ever taken any medication to treat HIV infection (i.e., ART).
11. Persons who have taken any medication by mouth (oral) in the preceding 3 months to prevent HIV infection (i.e., antiviral PrEP or PEP).
12. Persons who have received any medication by injection in the preceding 2 years to prevent HIV infection.
13. Persons who have been exposed in the preceding 3 months to known or suspected HIV-infected blood through percutaneous inoculation (e.g., needle stick) or through contact with an open wound, non-intact skin, or mucous membrane.
14. Persons who have been in lock up, jail, prison, or a juvenile correctional facility for more than 72 consecutive hours in the preceding 3 months.
15. Persons who have undergone tattooing, ear piercing or body piercing in the preceding 3 months, in which sterile procedures were not used, e.g., contaminated instruments and/or ink were used, or shared instruments that had not been sterilized between uses were used. A person may be eligible, for example, if a tattoo was applied by a state regulated entity with sterile needles and non-reused ink, or if ear or body piercing was done using single-use equipment.
16. Children 1 month of age or younger who were born to a mother with, or at risk for, an HIV infection; see risk factors above.
17. Children breastfed in the preceding 6 months by a mother with, or at risk for, an HIV infection; see risk factors above.
Clinical evidence of HIV for ineligible donors with relevant medical record review:
1. A prior positive or reactive screening test for HIV
2. Unexplained weight loss
3. Unexplained night sweats
4. Unexplained generalized rash
5. Blue or purple spots on or under the skin or mucous membranes typical of Kaposi’s sarcoma
6. Generalized lymphadenopathy (swollen lymph nodes) for longer than one month
7. Unexplained temperature of >100.5°F (38.06°C) for more than 10 days
8. Unexplained persistent cough or shortness of breath
9. Opportunistic infections
10. Unexplained persistent diarrhea, and/or
11. Unexplained persistent white spots or unusual blemishes in the mouth.
Physical evidence indicating high-risk behavior associated with HIV (ineligible donors):
1. Physical evidence for risk of sexually transmitted diseases and infections, such as perianal lesions, genital ulcerative disease, herpes simplex, mpox, or chancroid (when making a donor eligibility determination, consideration should be taken of these findings in light of other information obtained about the donor)
2. Physical evidence of non-prescription injection drug use such as needle tracks; the examination should include examination of tattoos, which might be covering needle tracks
3. Physical evidence of recent tattooing, ear piercing, or body piercing. Persons who have undergone tattooing, ear piercing, or body piercing in the preceding 3 months, in which sterile procedures were not used (e.g., contaminated instruments and or/ink were used), or instruments that had not been sterilized between uses were used. A person may be eligible, for example, if a tattoo was applied by a state regulated entity with sterile needles and non-reused ink, or if ear or body piercing was done using single-use equipment.
4. Generalized lymphadenopathy
5. Unexplained oral thrush
6. Blue or purple spots consistent with Kaposi’s sarcoma
7. Unexplained generalized rash or fever
Current Donor Screening Tests approved by the FDA:
1. For HIV-1: An FDA-licensed donor screening test either for anti-HIV-1 (including group O) or a combination test for anti-HIV-1 (including group O) and anti-HIV-2 and an FDA-licensed donor screening NAT for HIV-1, or a combination (multiplex) NAT; AND
2. For HIV-2: An FDA-licensed donor screening test either for anti-HIV-2 or a combination test for anti-HIV-1 (including group O) and anti-HIV-2
3. An FDA-licensed HIV antigen/HIV 1/O/2 antibody combination assay can be used for the simultaneous qualitative detection of HIV p24 antigen and antibodies to HIV-1 (including group O) and HIV-2. Such a licensed donor screening test should be used in combination with an HIV-1 NAT to adequately and appropriately test an HCT/P donor for HIV-1 and HIV-2.
Any HCT/P donor whose specimen tests negative (or non-reactive) for all assays (i.e., anti-HIV-1 (including group O), anti-HIV-2, or a combination test for those disease agents; and HIV-1 NAT) is considered to be negative (or non-reactive) when making a donor eligibility determination. Note that a negative (or non-reactive) test does not necessarily mean that a donor is eligible; donor screening also applies as described above.
Any HCT/P donor whose specimen tests positive (or reactive) using any of the assays (i.e., anti-HIV-1 (including group O), anti-HIV-2, a combination test for those disease agents, or HIV-1 NAT) is considered ineligible (21 CFR 1271.80(d)(1)).
Reference the FDA licensed donor screening tests here:
How does this impact the tissue industry? The American Association of Tissue Banks (AATB) provided feedback to the FDA February 6, 2025, requesting the FDA provides more clarity as there are some ambiguous interpretations for some of the risk factors that impact establishments determining donor eligibility. Read more about it here:
https://www.aatb.org/government-advocacy-correspondences
Reference the FDA guidance here:
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Keep checking back as we continue to follow updates and the impact on our industry!
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