Recommendations for Evaluating 
Donor Eligibility Using Individual 
Risk-Based Questions to Reduce the 
Risk of Human Immunodeficiency 
Virus Transmission by Blood and 
Blood Products 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or 
from the Internet at https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-
regulatory-information-biologics/biologics-guidances.  
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
May 2023 
 
  Contains Nonbinding Recommendations 
 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS .................................................................................................. 6 
A.  Donor Educational Material and Donor History Questionnaire ...................... 6 
B.  Donor Deferral ...................................................................................................... 8 
C.  Donor Requalification ........................................................................................ 10 
D.  Product Retrieval and Quarantine; Notification of Consignees of Blood and 
Blood Components .............................................................................................. 10 
E.  Product Disposition and Labeling ..................................................................... 11 
F.  Testing Requirements and Considerations ....................................................... 12 
IV.  IMPLEMENTATION .................................................................................................... 12 
V.  REFERENCES ................................................................................................................ 14 
 
i 
  Contains Nonbinding Recommendations 
 
 
Recommendations for Evaluating Donor Eligibility Using Individual 
Risk-Based Questions to Reduce the Risk of Human 
Immunodeficiency Virus Transmission by  
Blood and Blood Products 
 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
We, FDA, are issuing this guidance to provide recommendations for evaluating donor eligibility 
using individual risk-based questions.  This guidance provides you, blood establishments that 
collect blood or blood components, including Source Plasma, with FDAs revised donor deferral 
recommendations for individuals with increased risk for transmitting human immunodeficiency 
virus (HIV) infection.  We also recommend that you make corresponding revisions to your donor 
educational materials, donor history questionnaires and accompanying materials, along with 
revisions to your donor requalification and product management procedures.  This guidance 
supersedes the guidance entitled, Revised Recommendations for Reducing the Risk of Human 
Immunodeficiency Virus Transmission by Blood and Blood Products dated April 2020, updated 
August 2020 (April 2020 guidance).  The recommendations contained in this guidance apply to 
the collection of blood and blood components, including Source Plasma. 
 
The revised recommendations in this guidance reflect the Agencys current thinking on donor 
deferral recommendations for individuals with increased risk for transmitting HIV infection.  
Based on our review of the available science as discussed below, we recommend eliminating the 
screening questions specific to men who have sex with men (MSM) and women who have sex 
with MSM.  Instead, we recommend assessing donor eligibility using the same individual risk-
based questions relevant to HIV risk for every donor regardless of sex or gender. 
 
In addition, we recommend deferral of any individual taking medications to treat or prevent HIV 
infection (e.g., antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP), and post-exposure 
prophylaxis (PEP)).  FDA-approved antiretroviral drugs are safe and effective and can reduce the 
HIV viral load of individuals to undetectable levels as determined by nucleic acid tests (NAT).  
However, these antiretroviral drugs do not fully eliminate the virus from the body, and donated 
blood from individuals infected with HIV taking ART can potentially still transmit HIV to a 
1  Contains Nonbinding Recommendations 
 
 
transfusion recipient.  Although undetectable equals untransmissible for sexual transmission, this 
does not apply to transfusion transmission.  Further, the available data demonstrate that the use 
of PrEP and PEP may delay detection of HIV by currently licensed screening tests for blood 
donations, potentially resulting in false negative results.   
 
We have not changed the other recommendations and donor deferral time periods to reduce the 
risk of transfusion transmission of HIV from the April 2020 guidance.  Based on the Agencys 
careful evaluation of the available data, including data regarding the performance characteristics 
of NAT, FDA expects implementation of these revised recommendations will not be associated 
with any adverse effect on the safety or availability of the blood supply.   
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
The emergence of acquired immune deficiency syndrome (AIDS) in the early 1980s had 
profound effects on the United States (U.S.) blood system (Refs. 1-3).  Although initially 
identified in MSM and associated with male-to-male sexual contact, AIDS was soon identified as 
a blood-borne disease, transmitted by blood transfusion and receipt of clotting factor 
concentrates (Refs. 4-5).  Subsequently, AIDS was also disproportionately identified among 
people who exchanged sex for money or drugs and people who used intravenous drugs (Refs. 6-
7).   
 
The identification of risk factors for AIDS in 1983 informed the first blood donor education and 
deferral policy, which at that time was the only way to reduce the chance of transmission of 
AIDS through blood transfusion (Refs. 4-7).  Beginning in 1983, FDA issued recommendations 
for providing donor educational material about risk factors for AIDS (Refs. 8-10).  In addition, 
blood centers began asking risk questions and deferring from blood donation individuals who 
were at higher risk of having AIDS, even before the availability of tests to screen the blood 
supply.  These measures had a significant effect on reducing the risk of transmitting AIDS 
through blood transfusion (Ref. 11).  Still, thousands of transfusion recipients of blood and blood 
components and recipients of plasma-derived clotting factor concentrates were infected with 
HIV before the causative virus was identified (Refs. 1, 3, 9) and testing became possible. 
 
In 1984, the virus now known as HIV was determined to be associated with AIDS, which led to 
the development of blood donor screening tests.  FDA approved the first screening tests for 
antibodies against HIV in 1985 (Ref. 1).  Advances in HIV donor screening tests (e.g., HIV 
antibody assays, p24 antigen assays, and NAT), along with the use of donor educational material 
and specific deferral recommendations, progressively reduced the risk of HIV transmission from 
blood transfusion over time, from about 1 in 2,500 units prior to HIV testing in the 1980s to an 
estimated residual risk of about 1 in 1.47 million transfusions in 2022 (Refs. 12-13).  Moreover, 
2  Contains Nonbinding Recommendations 
 
 
no transmissions of HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) have been 
documented through U.S.-licensed plasma-derived products in the past three decades (Ref. 14). 
 
The specific donor history questions and deferral recommendations for behaviors and other 
factors that are known to increase the risk of HIV infection have evolved over time. 
Consequently, FDA has revised its deferral recommendations in a stepwise approach, supported 
by scientific data, including the epidemiology of HIV infection and the performance of HIV 
donor screening tests.  
 
Beginning in September 1985, FDA recommended that blood establishments indefinitely defer 
male donors who have had sex with another male, even one time, since 1977, because of the 
strong clustering of AIDS and the subsequent discovery of high rates of HIV infection among 
MSM (Ref. 15).  In subsequent years, FDA and the Department of Health and Human Services 
(HHS) held several public meetings, including scientific workshops and advisory committee 
meetings, to discuss blood donor deferral polices to prevent HIV transmission (Refs. 16-20).  In 
2010, an Interagency Blood, Organ & Tissue Safety Working Group (BOTS Working Group) 
consisting of representatives from the Centers for Disease Control and Prevention (CDC), Health 
Resources and Services Administration (HRSA), National Institutes of Health (NIH), HHS 
Office for Civil Rights (OCR), Office of the Assistant Secretary for Health (OASH), and FDA, 
was charged with exploring the feasibility of a data and science-driven policy change.  
Subsequently, the BOTS Working Group designed and facilitated the implementation of several 
research studies to help inform a potential policy change for MSM, including an assessment of 
quarantine release errors (Refs. 21-22); a study to evaluate comprehension of the donor history 
questions, which involved cognitive interviews with potential donors (Ref. 23); the Retrovirus 
Epidemiology Donor Study-II (REDS-II ) on behavioral risk factors for HIV among blood 
donors (Ref. 24); and, a study that surveyed the opinions of MSM regarding FDAs blood donor 
deferral policy (Ref. 25).  Data from these studies became available in 2014 and were presented 
to the BOTS Working Group, the HHS Advisory Committee on Blood and Tissue Safety and 
Availability (ACBSTA), and the FDA Blood Products Advisory Committee (BPAC).  In 
addition, epidemiologic data from countries that had shortened the deferral period for MSM, 
including Australia, indicated no safety concerns (Refs. 26-28).  The advisory committees agreed 
that the available scientific evidence supported a change in the deferral policy from an indefinite 
deferral to a 12-month deferral for MSM.  At the same time, they recommended further study of 
alternatives to time-based deferrals for MSM.  FDA subsequently concluded that the available 
evidence supported a change from the indefinite deferral for MSM, and in December 2015, 
recommended a 12-month deferral for MSM.   
 
Also in 2014, FDA launched the Transfusion Transmissible Infections Monitoring System 
(TTIMS) in the U.S., as part of the effort to advance blood donor deferral recommendations 
based on scientific data.  TTIMS monitors the safety of the U.S. blood supply and evaluates the 
rate of relevant transfusion transmitted infections (RTTIs) detected among blood donors before 
and after policy changes (Ref. 29).  Data from TTIMS in the two years following implementation 
of the 12-month donor deferral for MSM comparing the rates of HIV in those donating blood 
indicated that there was no increase in risk to the U.S. blood supply (Ref. 29).  Additionally, 
other countries, including the United Kingdom and Canada, had further moved to a 3-month 
deferral period for MSM, and there had been no reports from these countries suggesting safety 
3  Contains Nonbinding Recommendations 
 
 
concerns following the implementation of this change.  The totality of the surveillance 
information and the experience with a 3-month deferral in other countries, combined with the 
uniform use of NAT for HIV, HBV, and HCV, which can detect each of these viruses within a 3-
month period following initial infection, supported a recommendation for a 3-month deferral for 
MSM.  Consequently, in April 2020, based on FDAs evaluation of the available data, FDA 
recommended a 3-month deferral for MSM.  The recommendations in the April 2020 guidance 
were issued for immediate implementation to respond to the COVID-19 public health emergency 
and reported shortages in the U.S. blood supply. 
 
In addition to shortening the recommended deferral period for MSM, FDA concurrently 
evaluated the available scientific evidence that could support modification of several other blood 
donor deferrals related to risk for HIV.  Based on the experience in the United Kingdom and 
Canada, along with the detection characteristics of the NAT noted above, in April 2020, FDA 
also revised the recommended deferrals for individuals who exchange sex for money or drugs or 
engage in non-prescription injection drug use from indefinite to 3-month deferrals.  In addition, 
for similar reasons, the recommended 12-month deferral for other risk factors, including contact 
with another persons blood, receipt of a blood transfusion or a recent tattoo or piercing, was 
revised to 3 months.   
 
Although issued to address the COVID-19 public health emergency, the April 2020 guidance 
signaled FDAs intent to issue further guidance that would remain in effect after the end of the 
public health emergency.  The guidance also restated FDAs commitment to further investigate 
individual risk assessment as an alternative to time-based deferrals for MSM. 
 
FDA subsequently helped facilitate and funded the ADVANCE (Assessing Donor Variability 
And New Concepts in Eligibility) study, a pilot study intended to evaluate individual risk 
assessment strategies as an alternative to time-based deferrals for MSM (Ref. 30).  The 
ADVANCE study examined a number of HIV risk factors, such as anal sex and rates of HIV 
infection among MSM study participants.  In addition, the ADVANCE study determined the 
rates of PrEP and PEP use among MSM study participants (Ref. 31).   
 
FDA recognizes that other countries with similar HIV epidemiology as the U.S. have revised 
their donor eligibility criteria for MSM, based on risk assessments performed in these countries.  
Notably, the United Kingdom in 2021 and Canada in 2022 introduced a new approach for donor 
questioning based on individual risk factors (Refs. 32-36).  The approach is based on 
surveillance, epidemiology, and risk assessments that demonstrate that 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 (Refs. 32-37).  Thus, the United Kingdom 
and Canada have adopted an individual risk-based approach that asks all presenting blood donors 
(regardless of sex or gender), if they have had a new sexual partner or more than one sexual 
partner in the last 3 months, and if so, they are asked if they had anal sex (Refs. 34, 38).  
Individuals who report having a new sexual partner and anal sex or having more than one sexual 
partner and anal sex in the last three months are deferred from blood donation.  To date, the 
United Kingdom and Canada have not reported safety concerns following the implementation of 
this individual risk-based deferral policy.   
 
4  Contains Nonbinding Recommendations 
 
 
 
In considering the available data, we believe implementation of the individual risk-based 
approach recommended in this guidance will maintain the current high level of safety of blood 
and blood components, including Source Plasma in the U.S.  Consequently, we recommend 
individual risk-based questions that ask all donors about new or multiple sexual partners.  Under 
this approach, donors who report having a new sexual partner or more than one sexual partner in 
the past three months would be asked about a history of anal sex in the past three months.  The 
risk of HIV infection is significantly greater for anal sex when compared to other sexual 
exposures (Ref. 37).  Therefore, the deferral of individuals who report a new sexual partner or 
more than one sexual partner in the past three months and anal sex in the past three months 
would be expected to reduce the likelihood of donations by individuals with new or recent HIV 
infection who may be in the window period for detection of HIV by NAT.    
 
In addition, we recommend asking all donors about the use of medications to treat or prevent 
HIV infection (i.e., ART, PrEP and PEP).  FDA-approved antiretroviral drugs are safe and 
effective and can reduce the HIV viral load of individuals to undetectable levels as determined 
by conventional testing, and individuals should not stop taking their prescribed medication in 
order to donate blood.  However, these antiretroviral drugs do not fully eliminate the virus from 
the body, and donated blood can potentially still transmit HIV infection to a transfusion 
recipient.  Although undetectable still equals untransmissible for sexual transmission, this does 
not apply to transfusion transmission of HIV because a blood transfusion is administered 
intravenously and a transfusion involves a large volume of blood compared to exposure with 
sexual contact (Refs. 37, 39).  Further, the available data demonstrate that the use of PrEP or 
PEP may delay the detection of HIV by currently licensed screening tests for blood donations, 
potentially resulting in false negative results in infected individuals (Refs. 40-41).  The 
recommendation for a three-month deferral following the most recent dose of an oral medication 
to prevent HIV infection and a two-year deferral following the most recent injection of a 
medication to prevent HIV infection is based on the pharmacokinetics of the antiviral drugs, 
respectively (Ref. 42). 
 
Also, individuals have been identified who donated blood even though they were taking ART for 
a known HIV infection (Ref. 43).  Donated blood from individuals taking ART can potentially 
transmit HIV infection to a transfusion recipient (Ref. 39).  Consequently, we recommend asking 
all donors if they are currently taking any medication to treat an HIV infection and to 
permanently defer such donors. 
 
Finally, based on the available information, we are maintaining the other recommendations for 
deferral of individuals for HIV risk from the April 2020 guidance.  Surveillance information 
from the U.S. since implementation of the revised recommendations in April 2020, along with 
the uniform use of NAT which can detect HIV within a 3-month period following infection, 
support a three-month deferral for individuals who exchange sex for money or drugs or engage 
in non-prescription injection drug use, as well as individuals with other HIV risk factors, 
including contact with another persons blood, receipt of a blood transfusion or a recent tattoo or 
piercing (Ref. 44).   
 
5  Contains Nonbinding Recommendations 
 
 
We expect that implementation of the recommendations in this guidance will not adversely affect 
the safety or availability of blood components for transfusion (Ref. 45) or Source Plasma for 
further manufacture.  We will continue to monitor the safety of the blood supply using data from 
TTIMS and other available sources. 
 
 
III.  RECOMMENDATIONS 
 
The following sections summarize FDAs recommendations for blood donor deferral and 
requalification related to reducing the risk of HIV transmission by blood and blood products.   
 
A.  Donor Educational Material and Donor History Questionnaire 
 
1.  Blood establishments must provide educational material to donors before 
each donation explaining the risk of HIV transmission by blood and blood 
products and risk factors associated with HIV infection so that donors can 
self-defer (21 CFR 630.10(b)).  We recommend the donor educational 
material explain that individuals with risk factors for HIV need to be 
aware of the signs and symptoms associated with acute HIV infection, 
namely fever, enlarged lymph nodes, sore throat and rash.1  The 
educational material must be presented to donors in a manner they will 
understand, which may include oral, written, or multimedia formats, and 
must instruct the donor not to donate when a risk factor for HIV infection 
is present (21 CFR 630.10(b)).  We recommend the donor educational 
material indicate that individuals who have engaged in any activity or who 
have any risk factor that would result in a deferral (section III.B of this 
guidance) should not donate blood or blood components.  We also 
recommend the donor educational material indicate that individuals should 
not discontinue their prescribed medications, including PrEP or PEP, in 
order to donate blood.   
 
2.  We recommend that blood collection establishments update their donor 
educational material, donor history questionnaire (DHQ), including full-
length and abbreviated DHQs, and accompanying materials (e.g., flow 
charts) and processes to incorporate the recommendations provided in this 
guidance. 
 
3.  We recommend that the updated DHQ include the following elements to 
assess donors for risk: 
 
   
 
1 See CDC website at https://www.cdc.gov/hiv/basics/whatishiv.html. 
6  Contains Nonbinding Recommendations 
 
 
a.  A history ever of a positive2 test for HIV infection. 
b.  A history ever of taking any medication to treat HIV infection. 
c.  A history in the past 3 months of taking any medication by mouth 
(oral) to prevent HIV infection.  
d.  A history in the past 2 years of receiving any medication by 
injection to prevent HIV infection.  
e.  A history in the past 3 months of sex3 with a new partner.  
Individuals who report sex with a new partner in the past 3 months 
should be assessed for a history in the past 3 months of anal sex.  
 
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. 
 
If a donor has questions about whether, for the purposes of blood 
donation, they are considered to have had sex with a new partner, the 
blood establishments responsible physician must evaluate the donors 
responses and determine the eligibility of the donor (21 CFR 630.5 and 
630.10(a)).  
 
f.  A history in the past 3 months of sex with more than one partner.  
Individuals who report sex with more than one partner in the past 3 
months should be assessed for a history in the past 3 months of 
anal sex.   
g.  A history in the past 3 months of exchanging sex for money, drugs 
or other payment. 
h.  A history in the past 3 months of non-prescription injection drug 
use4. 
i.  A history in the past 3 months of sex with any of the following 
individuals:  a person with a history ever of a positive test for HIV 
infection, a person with a history in the past 3 months of 
exchanging sex for money, drugs or other payment, or a person 
with a history in the past 3 months of non-prescription injection 
drug use.  
 
2 In this context, positive includes a positive result on an HIV diagnostic assay and repeatedly reactive or reactive 
results on antibody or NAT blood donor screening assays. 
3 Unless specified as anal sex, throughout this guidance the term sex refers to having anal, oral, or vaginal sex, 
regardless of whether or not a condom or other protection is used. 
4 Non-prescription injection drug use includes not only the injection of non-prescription drugs, but also includes the 
improper injection of legally-prescribed drugs, such as injecting a prescription drug intended for oral administration 
or injecting a prescription drug that was prescribed for another individual. 
7  Contains Nonbinding Recommendations 
 
 
j.  A history in the past 3 months of receiving a transfusion of Whole 
Blood or blood components such as packed red blood cells, 
platelets, or plasma. 
k.  A history in the past 3 months of contact with blood of another 
individual through percutaneous inoculation such as a needle stick 
or through contact with a donors open wound or mucous 
membranes. 
l.  A history in the past 3 months of a tattoo, ear, or body piercing.  
m. A history in the past 3 months of syphilis or gonorrhea, or 
treatment for syphilis or gonorrhea. 
 
B.  Donor Deferral 
 
We recommend that you defer as follows: 
 
1.  Defer permanently an individual who has ever had a positive test result for 
HIV infection.5  
 
2.  Defer permanently an individual who has ever taken any medication to 
treat HIV infection (i.e., ART). 
 
3.  Defer for 3 months from the most recent dose, an individual who has taken 
any medication by mouth (oral) to prevent HIV infection (i.e., antiviral 
PrEP or PEP). 
 
4.  Defer for two years from the most recent injection, an individual who has 
received any medication by injection to prevent HIV infection (e.g., long-
acting antiviral PrEP or PEP).   
 
5.  Defer for 3 months from the most recent sexual contact, an individual who 
has had a new sexual partner in the past 3 months and who has had anal 
sex in the past 3 months. 
 
6.  Defer for 3 months from the most recent sexual contact, an individual who 
has had more than one sexual partner in the past 3 months and who has 
had anal sex in the past 3 months. 
 
7.  Defer for 3 months from the most recent event, an individual who has 
exchanged sex for money, drugs or other payment.  
 
 
5 A donor deferred indefinitely because of a repeatedly reactive or reactive result on an antibody or a NAT blood 
donor screening assay, respectively, may be considered for re-entry by a requalification method or process found 
acceptable for such purposes by FDA.  If the deferred donor is subsequently found to be eligible as a donor of blood 
or blood components by a requalification method or process found acceptable to such purposes by FDA, such a 
donor is no longer considered deferred (21 CFR 610.41(b)).  
8  Contains Nonbinding Recommendations 
 
 
8.  Defer for 3 months from the most recent event, an individual who has 
engaged in non-prescription injection drug use. 
 
9.  Defer for 3 months from the most recent sexual contact, an individual who 
has had sex with a person who has ever had a positive test for HIV 
infection.   
 
10.  Defer for 3 months from the most recent sexual contact, an individual who 
has had sex with an individual who has exchanged sex for money, drugs or 
other payment in the past 3 months.  If the individual has any uncertainty 
about when their sexual partner exchanged sex for money, drugs or other 
payment, defer the individual for 3 months from their most recent sexual 
contact.   
 
11.  Defer for 3 months from the most recent sexual contact, an individual who 
has had sex with an individual who has engaged in non-prescription 
injection drug use in the past 3 months.  If the individual has any 
uncertainty about when their sexual partner engaged in non-prescription 
injection drug use, defer the individual for 3 months from their most 
recent sexual contact.    
 
12.  Defer for 3 months from the most recent allogeneic transfusion, any 
individual who has a history of receiving an allogeneic transfusion of 
Whole Blood or blood components. 
 
13.  Defer for 3 months from the most recent exposure, any individual who has 
a history of contact with blood of another individual through percutaneous 
inoculation such as a needle stick or through contact with a donors open 
wound or mucous membranes.  
 
14.  Defer for 3 months from the most recent tattoo, ear or body piercing, an 
individual who has a history of tattoo, ear or body piercing.  However, 
FDA is not recommending deferral of individuals who have undergone 
tattooing within 3 months of donation, if the tattoo was applied by a state 
regulated entity with sterile needles and non-reused ink.  FDA also is not 
recommending deferral of individuals who have undergone ear or body 
piercing within 3 months of donation if the piercing was done using 
single-use equipment. 
 
15.  Defer for 3 months after completion of treatment, an individual who has 
had syphilis or gonorrhea, or received treatment for syphilis or gonorrhea, 
in the last 3 months. 
 
We recommend that you defer indefinitely an individual with hemophilia or related 
clotting factor deficiencies requiring treatment with clotting factor concentrates for 
reasons of donor safety, rather than based upon the risk of HIV infection. 
9  Contains Nonbinding Recommendations 
 
 
 
Note:  Under 21 CFR 630.5 and 630.10(a), FDA requires the responsible physician of a 
blood collection establishment to determine the eligibility of a donor, and to defer any 
donor if the donation could adversely affect the health of the donor or the safety of the 
blood or blood component. 
 
C.  Donor Requalification 
 
Under 21 CFR 630.35, you may determine a deferred donor to be eligible if, at the time 
of the current collection, the criteria that were the basis for the previous deferral are no 
longer applicable.  
 
1.  A donor deferred for any of the factors in section III.B.3-15 of this 
guidance may be eligible to donate after the deferral period (i.e., 3-month 
or 2-year period as applicable), provided the donor meets all other donor 
eligibility criteria. 
 
2.  A donor previously deferred indefinitely for exchanging sex for money, 
drugs or other payment, for engaging in non-prescription injection drug 
use, or, for a male donor, having sex with another man, may be eligible to 
donate, provided the donor is evaluated according to the recommendations 
in this guidance and the donor meets all donor eligibility criteria. 
 
3.  A male donor previously deferred for 3 months for having sex with 
another man, or a female donor previously deferred for 3 months for 
having sex with a man who had sex with another man, may be eligible to 
donate, provided the donor is evaluated according to the recommendations 
in this guidance and the donor meets all donor eligibility criteria. 
 
Note:  A donor deferred permanently for the factors in section III.B.1-2 of this 
guidance (i.e., a history of a positive test for HIV infection or a history of taking 
medication to treat HIV infection) is not eligible for requalification.   
 
D.  Product Retrieval and Quarantine; Notification of Consignees of Blood and 
Blood Components 
 
If you collected blood or blood components from a donor who tests reactive for HIV on 
that donation, or when you are made aware of other reliable test results or information 
indicating evidence of HIV infection (i.e., collected blood and blood components from a 
donor who has a  positive test for HIV infection or taken medication to treat an HIV 
infection (section III.B.1-2 of this guidance)), you must follow the HIV lookback 
requirements in 21 CFR 610.46. 
 
In addition, we recommend that you take the following actions if you determine that 
blood or blood components have been collected from a donor who should have been 
deferred according to the recommendations in section III.B.3-15 of this guidance, for 
10  Contains Nonbinding Recommendations 
 
 
reasons other than a positive test for HIV infection or medication to treat an HIV 
infection.  
 
1.  If you collected blood or blood components from a donor who should have 
been deferred according to the recommendations in section III.B of this 
guidance, we recommend that you quarantine and destroy any 
undistributed in-date blood or blood components collected from that 
donor.   
 
2.  If you distributed blood or blood components collected from a donor who 
should have been deferred according to the recommendations in section 
III.B of this guidance, we recommend that you notify consignees of the in-
date blood and blood components collected from the donor during the 
period that he or she should have been deferred.  We recommend that the 
consignee retrieve and quarantine the in-date blood and blood components 
collected from that donor during the period he or she should have been 
deferred.  We do not recommend retrieval and quarantine of plasma 
pooled for further manufacturing into products that are manufactured 
under processes that include validated viral clearance steps, which have 
been shown to be robust in the clearance of lipid-enveloped viruses. 
 
E.  Product Disposition and Labeling 
 
We recommend that you destroy or re-label blood or blood components that were 
collected from a donor who should have been deferred based on risk factors for HIV 
infection, or for a history of a positive test for HIV infection or for a history of taking any 
medication to treat HIV infection, in accordance with the recommendations in section 
III.B of this guidance.  If you re-label the blood or blood components as described in this 
section, they may be released for research.  
 
1.  You must use the following statements, as applicable, to prominently re-
label the blood or blood components originally collected for transfusion, 
in accordance with 21 CFR 606.121(f):  
 
NOT FOR TRANSFUSION:  Collected From a Donor Determined To 
Be At Risk For Infection With HIV,  
 
or 
 
NOT FOR TRANSFUSION:  Collected From a Donor Determined To 
Have HIV Infection, and with the BIOHAZARD legend 
 
and,  
 
Caution:  For Laboratory Research Only 
 
11  Contains Nonbinding Recommendations 
 
 
2.  You must use the following statements, as applicable, to prominently re-
label the blood or blood components, including Source Plasma, originally 
collected for further manufacture, in accordance with 21 CFR 
606.121(c)(10). 
 
  Caution:  Collected From a Donor Determined To Be At Risk For 
Infection With HIV,  
 
or 
 
  Caution:  Collected From a Donor Determined To Have HIV Infection, 
and with the BIOHAZARD legend, 
 
  and, 
 
  Caution:  For Laboratory Research Only 
 
F.  Testing Requirements and Considerations 
 
Section 610.40(a) (21 CFR 610.40(a)) requires establishments that collect blood or blood 
components to test each donation intended for transfusion or for use in manufacturing a 
product, for evidence of infection due to HIV type 1 (HIV-1) and HIV type 2 (HIV-2).  In 
addition, 21 CFR 610.40(b) requires you to use one or more approved screening tests as 
necessary to reduce adequately and appropriately the risk of transmission of HIV-1 and 
HIV-2.  FDA has considered the use of licensed donor screening tests for antibodies to 
both HIV-1 and HIV-2 as necessary to reduce adequately and appropriately the risk of 
transmission of HIV.  In addition, FDA recommends the use of licensed HIV-1 nucleic 
acid donor screening tests to meet the requirements under 21 CFR 610.40(b).  
 
You must defer a donor who tests reactive by a donor screening test for HIV-1 or HIV-2 
(21 CFR 610.41) and you must perform further testing using a supplemental test on 
donations that test reactive on a screening test, when available.  If no supplemental test is 
available, you must perform one or more licensed, approved or cleared tests as adequate 
and appropriate to provide additional information regarding the donors infection status 
(21 CFR 610.40(e)).  You must make reasonable attempts to notify a donor who has been 
deferred based on the results of tests for evidence of infection with a relevant transfusion-
transmitted infection (21 CFR 630.40).  Where appropriate, donors who are deferred 
because of reactive test results should be provided information about the need for medical 
follow-up and counseling.   
 
 
IV.  IMPLEMENTATION 
 
Licensed blood establishments must report changes to their approved application to FDA in 
accordance with 21 CFR 601.12.  
 
12  Contains Nonbinding Recommendations 
 
 
1.  Licensed blood establishments that revise their own DHQs and accompanying 
materials must report the change to FDA in a Prior Approval Supplement (PAS) 
Supplement under 21 CFR 601.12(b).  Include the following information in your 
PAS Supplement:  
 
a.  Form FDA 356h Application to Market a New or Abbreviated New 
Drug, or Biologic for Human Use.  
b.  Cover letter describing the request and contents of the supplement. 
c.  The DHQ and accompanying document(s).  Please highlight the 
modifications. 
 
2.  Licensed blood establishments that implement the DHQ and accompanying 
materials prepared by the AABB Donor History Task Force or the Plasma 
Proteins Therapeutic Association (PPTA) and found acceptable by FDA must 
report the changes to FDA in an annual report under 21 CFR 601.12(d), noting the 
date the process was implemented (21 CFR 601.12(a)(3)).   
 
Unlicensed establishments are not required to report this change to FDA.  
   
13  Contains Nonbinding Recommendations 
 
 
V.  REFERENCES 
 
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3.  Dubin C, Francis D, Closing the circle: a thirty-year retrospective on the AIDS/blood 
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4.  Centers for Disease Control and Prevention, Epidemiologic Notes and Reports 
Pneumocystis carinii Pneumonia among Persons with Hemophilia A, MMWR 1982, 
31:365-367. 
5.  Centers for Disease Control and Prevention, Epidemiologic Notes and Reports Possible 
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6.  Ginzburg HM, Intravenous drug users and the acquired immune deficiency syndrome, 
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14  Contains Nonbinding Recommendations 
 
 
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donor-deferrals-in-the-era-of-nucleic-acid-testing-public-workshop-request-for.    
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https://public3.pagefreezer.com/browse/HHS.gov/28-07-
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Europe, Vox Sanguinis 2014, 107:420-427.  
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transfusion-transmitted human immunodeficiency virus infection in Australia subsequent 
15  Contains Nonbinding Recommendations 
 
 
to implementing a 12-month deferral for men who have had sex with men, Transfusion 
2010, 50:2722-2730. 
28.  Lucky TTA, Seed CR, Waller D, et al., Understanding noncompliance with selective 
donor deferral criteria for high-risk behaviors in Australian blood donors, Transfusion 
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monitoring system:  a tool to monitor changes in blood safety, Transfusion 2016, 
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31.  Custer B, Whitaker B, Pollack, L, et al., HIV Risk Behavior Profiles Among Men Who 
Have Sex with Men Interested in Donating Blood:  The Assessing Donor Variability and 
New Concepts in Eligibility (ADVANCE) Study, medRxiv, 2023.04.08.23288320; doi: 
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donation-safety-check/. 
39.  FDA Safety Communication.  Important Information for Potential Donors of Blood and 
Blood Products:  Individuals who have ever tested positive for HIV should not donate 
16  Contains Nonbinding Recommendations 
 
 
blood.  December 2019.  https://www.fda.gov/vaccines-blood-biologics/safety-
availability-biologics/important-information-potential-donors-blood-and-blood-products. 
40.  deSouza MS, Pinyakorn S, Akapirat S, et al., Initiation of anti-retroviral therapy during 
acute HIV-1 infection leads to a high rate of nonreactive HIV serology, Clin. Infect. Dis. 
2016, 63:555-561. 
41.  Seed CR, Yang, H, Lee JF, Blood safety implications of donors using HIV pre-exposure 
prophylaxis, Vox Sanguinis 2017, 112:473-476. 
42.  Association of the Advancement of Blood and Biotherapies.  Association Bulletin #22-
03, Updated Recommendations on Donor Deferral for Use of Antiretroviral Medications 
for HIV Prevention and Treatment including Long-Acting Injectable PrEP and the Impact 
on Blood Safety.  https://www.aabb.org/docs/default-source/default-document-
library/resources/association-bulletins/ab22-03.pdf. 
43.  Custer B, Quiner C, Haaland R, et al., HIV antiretroviral therapy and prevention use in 
US blood donors:  a new blood safety concern, Blood 2020, 36(11):1351-1358.  
44.  Grebe E, Di Germanio C, Stone M, et al., HIV incidence in US first-time blood donors 
during 12-month and 3-month MSM deferral policy periods on behalf of the US TTIMS 
program (abstract), 2023, 33rd Regional ISBT Congress, Gothenburg, Sweden. 
45.  Whitaker BI, Huang Y, Gubernot D, Eder A, Forshee R, Modeling the effect of an 
individual-risk based deferral policy for sexual behaviors on blood donations in the US 
(abstract), 2023, 33rd Regional ISBT Congress, Gothenburg, Sweden.  
17