MSM and blood donation: shifting to individualized risk assessment

Walter, a married gay man, and his husband, Bill, who have been in a mutually exclusive sexual relationship for many years, hear an urgent appeal for blood donors on the radio and decide to overcome their fear of needles and make an appointment to donate blood. While waiting to be seen by the screener at the Toronto fixed site, they see their neighbor, Casanova, who is always boasting about his success finding new lady partners on Tinder.

Who do you think will be eligible to donate?

Blood safety depends on donor selection, testing, and for some components, pathogen reduction. In many countries, including the US, Canada, the UK, and Australia, blood establishments performing collection, testing, and distribution are highly regulated, and a standardized donor health questionnaire (DHQ) and criteria manual are used. The DHQ questions divide donors into standard and higher risk groups, with the higher risk group undergoing additional testing or, more often, deferring from donation for a period of time or indefinitely. If testing is unavailable for an infectious agent in a nonpathogen-reduced component, donor selection is vital to reduce risk. Once testing is developed, the importance of donor selection decreases.

Donor criteria for gay, bisexual, and other men who have sex with men (gbMSM) were introduced in the 1980s, when it was recognized that AIDS could be transmitted by blood.^1,2  Initially, donors were provided written materials instructing them to self-defer if they fell into risk categories, including male homosexuals with multiple partners. These policies are thought to have resulted in an approximately 90% reduction in the risk of AIDS/HIV transfusion transmission in high-risk areas, such as San Francisco.^2,3  Once antibody testing began, interviews with HIV-positive donors indicated that many did not necessarily identify as gay or have multiple partners. In 1985, the deferral for a man who has had sex with another man even once since 1977 was mandated by the Food and Drug Administration (FDA); 1977 was thought to be the time AIDS appeared in North America.⁴  Many other countries introduced similar criteria. Many other criteria were also put in place to reduce the risk of HIV and/or hepatitis B and C transmission, including deferrals for having an HIV-positive sexual partner, for paying or receiving money or drugs for sex, or for using injection drugs.⁴ 

The epidemiology of HIV differs in different geographic areas. This discussion is focused on deferral policies in countries where gbMSM have a higher prevalence and incidence of HIV compared with the general population.

The relative importance of donor screening questions for HIV risk decreased with the introduction of increasingly sensitive tests for HIV 1/2 antibodies, antigen testing (p24), and eventually nucleic acid testing (NAT). Improved automation, process control, and quality systems have virtually eliminated errors in testing and blood center quarantine procedures. The window period, when donors may be infectious but have negative test results, is estimated at 9 days for NAT tests performed in minipools in North America. Additionally, individuals are more aware of risk factors for HIV transmission, and rapid, confidential testing is easily available.

However, criteria for gbMSM were slow to change, in part because of a highly precautionary system born out of the tragedy of transmission of HIV and hepatitis C (known as non-A, non-B hepatitis at the time) to thousands of blood- and plasma-derived clotting factor recipients in the 1980s and early 1990s.⁵ 

In 2000, Australia implemented a 12-month deferral policy for gbMSM, with no increase in HIV positivity rates.⁶  Risk modeling done in several countries suggested that moving from a permanent to a 5-year or 12-month deferral would lead to a negligible increase in HIV risk of under 1 in 5 million transfusions.⁷  The US REDS-III Blood Donation Rules Opinion Study (BloodDROPS), in surveys of the gbMSM community and noncompliant gbMSM who donated blood, demonstrated that the HIV prevalence in gbMSM donors was 0.25%, considerably lower than the estimated rate in the general US gbMSM population.⁸ 

Based on the above, in addition to advocacy group pressure, many countries moved from a permanent deferral for gbMSM to progressively shorter time-based deferrals.⁹  In Canada, the permanent deferral was replaced by a 5-year, 12-month, and 3-month deferral in 2013, 2016, and 2019, respectively.¹⁰  In the US, the FDA issued revised recommendations for reducing the risk of HIV transmission in 2015, including a 12-month deferral for gbMSM, and again in 2020, including a 3-month deferral.¹¹ 

Postimplementation monitoring studies (Table 1) showed that changing to shorter deferral periods maintained safety.¹² 

Although shorter time-based deferrals allow some men who had remote experiences with male-to-male sex to donate, they still result in the deferral of most sexually active gbMSM. Additionally, asking male donors about sex with another male can be seen as stigmatizing and the deferrals seen as discriminatory, generating “ban the ban” campaigns and cancelled blood drives on university campuses, and legal challenges in several countries.^1,13  Under these criteria, our possible donors, Walter and Bill, would be deferred, while Casanova may likely be eligible.

Several countries, including Spain and Italy, implemented policies based on sexual behaviors considered to be at higher risk, regardless of whether the partner is same sex or opposite sex; these are sometimes referred to as gender-neutral or risk-based behavior policies. For example, in Spain, donors were deferred for 12 months after sex with more than 1 concurrent partner, or sex with an occasional partner. In Italy, donors were deferred for 4 months after sexual contact with a new or occasional partner whose risk behavior is unknown, and indefinitely deferred for usual/recurrent sex with more than 1 partner whose risk behaviors are unknown or multiple new partners. Published HIV rates, including NAT-only positives, were higher compared with countries using time-based deferrals; it is unclear if this was related to the criteria, methods of questionnaire administration (use of medical doctors), and/or poor donor understanding and compliance. Both differences in blood center functioning and higher donor HIV rates impeded adoption on these approaches in other countries.^14-16 

UK policies evolved from a permanent deferral for male-to-male sex to a 12- and then 3-month deferral. The UK FAIR (For the Assessment of Individual Risk) steering group, comprising the UK blood services, Public Health England, Nottingham University researchers, and stakeholders including 2SLGBTQI+ (two-spirit, lesbian, gay, bisexual, transgender, queer, intersex, and other people who identify as part of sexual and gender diverse communities) groups, reviewed the literature on individual risk sexual behaviors and markers of risk. Focus groups and surveys of stakeholders were undertaken to assess the feasibility and acceptability of potential questions. FAIR recommended deferring donors with a new partner or multiple sexual partners in the last 3 months only if they had anal sex, since anal sex carries the highest rate of HIV transmission and deferral of all donors with a new partner or multiple partners would have too great an impact on the adequacy of the blood supply.¹⁷  Donors who participated in chemsex (use of drugs such as amyl nitrite to enhance sexual experience) in the past 3 months are also deferred since this was identified as a marker of HIV risk. These recommendations were implemented by the blood services in the UK in 2021.

In 2017, the Canadian federal government funded research programs, administered by Canadian Blood Services and Héma-Québec, the two Canadian blood suppliers, to develop the evidence for a sexual risk behavior approach for whole blood, plateletpheresis, and source plasma donation. Research themes, developed at a kickoff meeting, included safety, operational feasibility, acceptability to donors and gbMSM community members, and the impact of pathogen reduction. Nineteen projects at 11 different research sites were funded, resulting in over 20 publications to date.¹⁸  Many studies, such as risk modeling of possible changes, risks for HIV infection identified in a prospective cohort of gbMSM, operational feasibility of various policies, and acceptability of various approaches to donors and high-interest stakeholder groups, proved critical to supporting a successful regulatory submission to move to an approach very similar to FAIR.^19-23 

Criteria implemented at Canadian Blood Services for all donors and all donation types (whole blood, plasma and platelet pheresis, source plasma) in September 2022 are shown in Figure 1. Implementation was preceded by an extensive staff training program. Héma-Québec implemented identical criteria, first for source plasma and then for all other donation types, slightly later in 2022. Results in the first 6 months postimplementation have shown no increase in HIV rates, no HIV NAT-only positive donors, few complaints from donors, and lower than expected donor deferral rates. Walter and Bill may now be eligible, while Casanova may find himself deferred, depending on specific sexual behaviors. Table 2 shows actual compared with predicted deferral rates.^19,24  A similar discordance between expected and observed rates was seen at Héma-Québec, the blood supplier for the province of Québec. Reasons for this discordance are unclear but may relate to how thoughtful people are about answering survey questions compared with the actual donor questionnaire. As expected, younger donors are more likely to be deferred by the new criteria. These observations would be strengthened by a longer observation period. Additionally, an anonymous donor survey will be performed in late 2023 to access compliance and provide some data on the number of currently eligible male donors who previously would have been deferred. It is possible that noncompliance has been reduced as some gbMSM may not have answered questions truthfully that they considered discriminatory.

The US ADVANCE (Assessing Donor Variability and New Concepts in Eligibility) Study, funded by the FDA, enrolled close to 1600 sexually active gbMSM, from 18 to 39 years old in 8 participating communities. Study participants completed a questionnaire and were tested for HIV antiretroviral drugs (medications that can be used as pre-exposure prophylaxis for HIV, known as PrEP). The goal of the study was to evaluate whether sexual behavior risk questions could identify participants who recently became infected with HIV.²⁵  The FDA used study data, as well as implementation data and risk modeling studies performed internationally, to issue recommendations for evaluating donor eligibility using individual risk-based questions to reduce the risk of HIV transmission by blood and blood products (in draft guidance in January 2023, final guidance in May 2023). The questions and criteria proposed are similar to what has been implemented in the UK and Canada, shown in Figure 1.²⁶  The Association for the Advancement of Blood & Biotherapies has incorporated these changes into the DHQ version 4.0 and prepared resources to assist in training and implementation.²⁷ 

Many other countries, such as Israel, France, the Netherlands, and Germany, have implemented or will soon implement criteria based on sexual risk behaviors and remove time-based deferrals for gbMSM.

Some future considerations are outlined in Table 3. PrEP therapy with antiretroviral medications is highly effective at preventing sexual transmission of HIV. However, if donors get infected by HIV on or shortly after discontinuing PrEP, viral kinetics and the host immune response may be altered, possibly prolonging testing window periods. Many blood centers have added PrEP- related criteria, deferring some otherwise eligible donors.²⁸ 

Treatment of HIV with antiretroviral medications is highly effective at reducing sexual transmission risk, leading to public health messaging that undetectable equals untransmissible (U = U). However, this is not necessarily the case for transfusion of a large volume intravenously. Communicating this message is challenging.

Pathogen reduction technologies are used in manufacturing plasma protein derivatives and more recently have been introduced for platelets and plasma for transfusion. These technologies result in several log reduction of many pathogens, such as HIV, hepatitis B virus, and hepatitis C virus. Theoretically, criteria could be less stringent when pathogen reduction technology is used. A good place to start may be PrEP/post-exposure prophylaxis criteria.

Trans or transgender is an umbrella term that refers to people whose current gender identity differs from their biological sex assigned at birth. Trans people may identify as trans males (assigned female at birth, gender identity male), as trans females (assigned male at birth, gender identity female), or as nonbinary. Blood centers have grappled with several complex issues in attempting to respectfully screen trans donors while ensuring donor and recipient safety.²⁹  Screening is simplified by the use of a sexual risk behavior approach, since all donors are asked the same questions, regardless of their sex or gender, and the questions focus on behavior, regardless of the sex or gender of the donor's sexual partner(s) (gender-neutral questions). However, most blood centers do not have a nonbinary option, partly due to software limitations.³⁰ 

After many decades of using male-to-male sex as a surrogate marker for high-risk sexual behavior, blood services are moving to criteria based on sexual risk behaviors in all donors. Initial implementation in the UK and Canada have shown promising results but would be strengthened by further observation. These changes are an important step toward a more inclusive approach to blood donor selection.

Mindy Goldman is on the biomedical advisory board of ITL. She has given a presentation at a Roche corporate event about donor diversity.

Mindy Goldman: There is nothing to disclose.