Infection Pressure in Men Who Have Sex With Men and Their Suitability to Donate Blood

Abstract

Background:
Deferral of men who have sex with men (MSM) from blood donation is highly debated. To assist in defining MSM donor deferral policies, we investigated their suitability to donate blood.

Methods:
We compared the antibody prevalence of 10 sexually and transfusion transmissible infections (TTI) among 583 MSM from the Amsterdam Cohort Studies and 583 age-matched repeat male blood donors. MSM were classified as low-risk (lr) or medium-to-high-risk (hr) based on self-reported sexual behavior and as qualified or unqualified using Dutch donor deferral criteria other than male-to-male sex. Infection pressure (IP) was defined as the number of antibody-reactive infections, with class A infections (HIV-1/2, HBV, HCV, HTLV-1/2, syphilis) given double weight as compared to class B infections (CMV, HSV-1/2, HHV-8, HEV, Parvovirus B19).

Results:
Donors had a lower median IP than qualified lr-MSM and qualified hr-MSM (2[IQR-1-2]) versus 3[IQR 2-4), p<0.001). A low IP was found in 76% of donors, 39% of qualified lr-MSM, and 27% of qualified hr-MSM. The prevalence of class A infections did not differ between donors and qualified lr-MSM but was significantly higher in qualified hr-MSM and unqualified MSM. Recently acquired class A infections were detected in hr-MSM only. Compared to blood donors, human herpesviruses were more prevalent in all MSM groups (p<0.001), and prevalence increased with self-reported risk behavior.

Conclusion:
IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood safety with regards to class A infections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation.

Full text

Clinical Infectious Diseases
• CID 2018:XX (XX XXXX) • 1
Blood Donation byMSM
Infection Pressure in Men Who Have Sex With Men and
eir Suitability to DonateBlood
Ward P.H.van Bilsen,1,a Hans L.Zaaijer,2,3,a AmyMatser,1 Katjavan den Hurk,4 EdSlot,2 Maarten F.Schim van der Loeff,1,3 MariaPrins,1,3,b and
Thijs J.W.van de Laar2,b
1Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, 2Department of Blood-borne Infections, Sanquin Research, 3Department of Internal Medicine,
Amsterdam Infection and Immunity Institute, Academic Medical Center, and 4Department of Donor Studies, Sanquin Research, Amsterdam, The Netherlands
Background. Deferral of men who have sex with men (MSM) from blood donation is highly debated. We therefore investigated
their suitability to donate blood.
Methods. We compared the antibody prevalence of 10 sexually and transfusion-transmissible infections (TTIs) among 583
MSM and 583 age-matched repeat male blood donors. MSM were classied as low risk (lr) or medium-to-high risk (hr) based on
self-reported sexual behavior and as qualied or unqualied using Dutch donor deferral criteria. Infection pressure (IP) was dened
as the number of antibody-reactive infections, with class Ainfections (human immunodeciency virus-1/2, hepatitis B virus, hep-
atitis C virus, human T-cell lymphotropic virus-1/2, syphilis) given double weight compared to class B infections (cytomegalovirus,
herpes simplex virus-1/2, human herpesvirus 8, hepatitis E virus, parvovirus B19).
Results. Donors had a lower median IP than qualied lr-MSM and qualied hr-MSM (2 [interquartile range {IQR}, 1–2] vs 3
[IQR, 2–4]; P<.001). Low IP was found in 76% of donors, 39% of qualied lr-MSM, and 27% of qualied hr-MSM. e prevalence of
class Ainfections did not dier between donors and qualied lr-MSM but was signicantly higher in qualied hr-MSM and unqual-
ied MSM. Recently acquired class Ainfections were detected in hr-MSM only. Compared to blood donors, human herpesviruses
were more prevalent in all MSM groups (P<.001).
Conclusions. IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood
safety with regard to class Ainfections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation.
Keywords. blood donation; men who have sex with men; deferral policy; infection pressure.
In response to the AIDS epidemic, lifetime donor deferral of
men who have sex with men (MSM) was introduced to increase
blood safety in the 1980s [1, 2]. The scientific rationale for
MSM donor deferral has weakened over time, as nucleic acid
amplification testing (NAAT) for human immunodeficiency
virus (HIV) has substantially decreased the window period,
during which HIV cannot yet be detected but may be transmit-
ted via transfusion [3, 4]. As a result, public and political pres-
sure to liberalize deferral policies has caused many high-income
countries to change from permanent to temporary MSM donor
deferral [1, 2, 5].
Currently, in Europe, donor deferral of MSM varies from
“gender neutral” policies that are based on sexual practices
without considering the gender of the sex partner (Spain, Italy,
and Portugal), to temporary deferral of 3–12months aer last
male-to-male sex contact (eg, United Kingdom, Germany,
France, and the Netherlands), to permanent deferral (Denmark,
Austria, and Croatia) [6]. In the Netherlands, MSM deferral is
continued for sexually active MSM, dened as having male-to-
male sexual contact in the past year. Despite a leveling o of the
HIV incidence among Dutch MSM in recent years, MSM remain
the major risk group for HIV infection in the Netherlands [7].
In 2016, 67% of the 816 new HIV diagnoses were in MSM who
comprise an estimated 3% of the adult male population [7]. In
addition, a recent phylogenetic study suggested that 24 of 32
(75%) Dutch and Flemish male donors diagnosed with HIV in
the period 2005–2014 acquired their HIV infection through
male-to-male sex [8].
To achieve a harmonized European approach on MSM donor
deferral, the Council of Europe has requested epidemiological
and behavioral data to support an evidence-based recommen-
dation to both protect the blood supply and avoid stigmatiz-
ing population groups who are deferred unreasonably [9, 10].
High-quality studies investigating the risk of transfusion-trans-
missible infections (TTIs) in MSM who donate blood are scarce
[11, 12]. In this study we investigated the suitability of MSM to
donate blood by comparing the antibody reactivity to 10 sexu-
ally transmitted and/or blood-borne infections between MSM
MAJOR ARTICLE
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/ciy596
Received 10 February 2018; editorial decision 12 May 2018; accepted 24 July 2018; published
online July 25, 2018.
aW. P.H. B.and H.L. Z.contributed equally to this work.
bM. P.and T.J. W.L.contributed equally to thiswork.
Correspondence: W. P. H. van Bilsen, Public Health Service of Amsterdam, Department
of Infectious Diseases, Nieuwe Achtergracht 100, 1018 WT Amsterdam, The Netherlands
(wvbilsen@ggd.amsterdam.nl).
Clinical Infectious Diseases® 2018;XX(XX):1–8
STANDARD
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2 • CID 2018:XX (XX XXXX) • van Bilsen etal
and the general male donor population. We hypothesized that
MSM with self-reported low-risk behavior pose a low threat to
blood safety if their infection pressure (IP) is comparable to that
of male donors.
MATERIALS AND METHODS
Study Population
The Amsterdam Cohort Studies (ACS) among MSM is an open
prospective cohort study initiated in 1984 to investigate the
prevalence, incidence, and risk factors of HIV and other blood-
borne and sexually transmitted infections [13]. Participants
biannually visit the Public Health Service of Amsterdam, where
they give blood for testing and storage and complete a stan-
dardized questionnaire about sexual behavior in the preceding
6 months. We selected all HIV-negative MSM with an ACS
visit between January and August 2016. The ACS questionnaire
was extended with donor eligibility questions from the Dutch
Donor Health Questionnaire (DHQ) and questions regarding
the willingness to donateblood.
For a primary comparison group, we randomly selected
age-matched repeat male blood donors from blood collection
sites in Amsterdam between January and August 2016. Because
repeat donors went through several selection and testing cycles,
a second comparison group included all men who registered as
a (potential) new blood donors at a collection site in Amsterdam
in that period.
Routine Donor Screening
Upon registration as blood donor and at every donation visit,
donors complete a standardized DHQ, and their blood is
screened for TTIs if no risk factors for donation are reported.
New and repeat donors are routinely tested for antibodies
to HIV types 1 and 2 (HIV-1/2), hepatitis B surface antigen
(HBsAg), antibodies to hepatitis B core antigen (anti-HBc),
antibodies to hepatitis C virus (HCV), and antibodies to human
T-cell lymphotropic virus types 1 and 2 (HTLV-1/2; new
donors only) using chemiluminescent immunoassays (PRISM,
Abbott Laboratories), and for syphilis antibodies using par-
ticle agglutination test (TPHA PK 2000, Trinity Biotech). In
addition, donors are tested for HIV-1/2 RNA, hepatitis B virus
(HBV) DNA, and HCV RNA in pools of 6 donations (COBAS
6800 MPX assay, Roche Diagnostics). Confirmation testing
includes alternative NAT for HIV-1/2, HBV, and HCV (Cobas
AmpliPrep/Cobas TaqMan version 2.0, Roche Diagnostics);
HBsAg neutralization (Architect HBsAg confirmatory test,
Abbott); immunoblots for HIV-1/2, HCV, HTLV-1/2, and
syphilis (INNO LIA Score, Fujirebio); and Venereal Disease
Research Laboratory testing. Anti-HBc–reactive donors are
tested for anti-HBs (Architect Anti-HBs, Abbott) and require
an antibodies to hepatitis B surface antigen (anti-HBs) titer of
200 IU/mL for eligibility [14, 15].
Laboratory Methods
MSM and repeat donors were screened for antibodies against
10 sexually transmitted and/or blood-borne infections, cate-
gorized in classes Aand B.Class Aincluded the 5 infections
that are part of routine donor screening (ie, HIV, HBV, HCV,
HTLV, and syphilis). Class B infections included cytomegalo-
virus (CMV), herpes simplex virus 1 and 2 (HSV-1/2), human
herpesvirus 8 (HHV-8), hepatitis E virus (HEV), and parvovi-
rus B19. Class B infections were included as they are potential
markers for (sexual) risk behavior for which the estimated
prevalence in the general Dutch population varies from very
low (HHV-8) to very high (parvovirus B19). Serological assays
included Murex HIV antigen/antibody, CMV immunoglobulin
G2, and HSV-1/2 immunoglobulin G (IgG) (Liaison, Diasorin);
anti-HCV, anti-HBc II, HTLV-1/2, and Syphilis TP (Architect,
Abbott Laboratories); Kaposi sarcoma–associated herpes-
virus/HHV-8 IgG enzyme-linked immunosorbent assay kit
(Advanced Biotechnologies); HEV IgG (Wantai Pharmacology
Pharmacy Enterprise); and parvovirus B19 IgG (Biotrin). MSM
found to be anti-HBc reactive were subsequently tested for
HBsAg and anti-HBs (Architect, Abbott Laboratories).
Study Variables
Infection Pressure
The IP for each participant was defined as the number of anti-
body-reactive infections, with antibody-reactive class Ainfec-
tions arbitrarily given double weight. The cutoff to distinguish
between low and high IP was set at the median IP determined in
repeat male donors. If antibodies against any class Ainfection
were detected, the IP was defined as high.
Recent Class AInfections
Recent class Ainfections were defined as antibody seroconver-
sion within the preceding year. Antibody seroconversion was
determined using previous test results and testing stored serum
samples. This 1-year period was set because the current eligibil-
ity criteria for blood donation require 1year without male-to-
male sexual contact.
Sexual Risk Behavior
MSM were categorized as low risk (lr-MSM) or medium-
to-high risk (hr-MSM) based on self-reported sexual beha-
vior during the preceding year. Low-risk sexual behavior was
defined as either (i) no anal intercourse, (ii) a monogamous
relationship with a steady male partner (including condomless
sex with that partner), or (iii) consistent condom use during
anal intercourse with casual partner(s). All other MSM were
categorized as hr-MSM. HIV preexposure prophylaxis was not
included in MSM risk classification.
Qualication of MSM as Potential BloodDonors
All blood donors fulfilled the Dutch eligibility criteria for dona-
tion, as assessed in the DHQ. Currently, in the Netherlands,
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• CID 2018:XX (XX XXXX) • 3
Blood Donation byMSM
MSM face a temporary deferral of 12 months after the last
male-to-male sexual contact. In this study, MSM were qualified
as potential blood donors if they did not report any of the fol-
lowing Dutch permanent deferral criteria: a history of inject-
ing drug use or commercial sex work, blood transfusion, or
transplantation after 1980; a UK visit >6months between 1980
and 1996; a family history of Creutzfeldt-Jakob disease; a pre-
vious diagnosis with HIV, HCV, HTLV, or syphilis; or an active
HBV infection. Note that permanent deferral criteria in the
Netherlands might differ from those used in other countries.
Willingness toDonate
For MSM, intention to donate was measured on a 7-point Likert
scale (ranging from completely disagree to completely agree)
using the following statement: “If Iwould be allowed to donate
blood, Iwould apply as a blood donor in the future.” We distin-
guished moderate to high intention (score 4–7) from no to low
intention (score 1–3).
Statistical Analysis
Age, IP, seroprevalence per infection, and number of recent class
Ainfections of qualified lr-MSM, qualified hr-MSM, unquali-
fied lr-MSM, and unqualified hr-MSM were compared to those
of repeat donors using the unpaired t test (normal distributed
numerical data), the Mann-Whitney U test (nonnormal distrib-
uted numerical data), or the χ2 test/Fisher exact test (categorical
data). MSM with missing data on risk behavior and/or eligibility
were excluded from the main analysis. Additional analyses were
performed to determine differences in the main outcomes within
the group of qualified lr-MSM. AP value≤.05 was considered
significant. Analysis was performed using Stata Intercooled ver-
sion 13.1 software (StataCorp, College Station, Texas).
Sensitivity Analyses
Sensitivity analyses were performed to assess the impact of
missing data. In addition, we repeated our analyses on IP using 2
alternative methods to calculate IP. First, class Ainfections were
weighted 4 times more than class B infections. Second, IP was
defined as the individual predictive probability of class Ainfec-
tions given all individual class B infections (Supplementary
Data 2).
RESULTS
Study Population
During the study period, 583 of 604 (97%) MSM agreed to par-
ticipate in our study. They were age-matched to 583 repeat male
blood donors. We then excluded MSM with missing data on
sexual risk behavior and/or eligibility, leaving 520 MSM for the
main analysis (Figure1). The median age of MSM and repeat
donors was 42years (interquartile range [IQR, 35–48years for
MSM and 34–48years for donors). New donors had a median
age of 28years (IQR, 24–34).
Based on our sexual risk criteria, 245 of 520 (47%) were
lr-MSM, and 275 of 520 (53%) were hr-MSM. Among lr-MSM,
52 of 245 (21%) reported no anal intercourse in the preceding
year, 60 of 245 (24%) had a monogamous relationship, and 133
of 245 (54%) consistently used condoms during anal sex with
casual partners. Based on our qualication criteria for blood
donation, 380 of 520 (73%) MSM qualied as potential donors,
and 140 of 520 (27%) MSM did not qualify. Of those unqualied,
92 reported a history of syphilis, 20 reported commercial sex
work, 22 lived in the United Kingdom between 1980 and 1992, 9
had a history of transplantation, 7 received a blood product aer
1980, 4 had ever injected drugs, 2 reported a family history of
Creutzfeldt-Jakob disease, and 1 had a previous HCV diagnosis.
e majority of MSM had a moderate-to-high intention to
donate (380/520 [73%]; median score, 5 [IQR, 4–6]). Intention
did not dier among qualied lr-MSM, qualied hr-MSM,
unqualied lr-MSM, and unqualied hr-MSM (P=.223).
Infection Pressure
The median IP among repeat donors (2 [IQR, 1–2]) was sig-
nificantly lower than among qualified lr-MSM (3 [IQR, 2–4]),
qualified hr-MSM (3 [IQR, 2–4]), unqualified lr-MSM (4 [IQR,
3–5]), and unqualified hr-MSM (4 [IQR, 4–6]) (P<.001 for all;
Figure2; Supplementary 1). The proportion of participants with
a low IP (≤2) was 76% (443/583) in repeat donors, 39% (76/197)
in qualified lr-MSM, 27% (50/183) in qualified hr-MSM, 13%
(6/48) in unqualified lr-MSM, and 4% (4/92) in unqualified
hr-MSM (P<.001 forall).
Class AInfections
None of the donors or MSM had HIV-1/2 antibodies. Anti-
HCV was detected in 1 of 48 (2%) unqualified lr-MSM, 2 of 92
(2%) unqualified hr-MSM, and 1 of 361 (1%) new donors. Anti-
HTLV-1/2 was detected in 1 of 92 (1%) unqualified hr-MSM. None
of the repeat donors or qualified lr-MSM had antibodies against
syphilis, while 2 of 361 (1%) new donors, 5 of 183 (3%) qualified
hr-MSM, 23 of 48 (48%) unqualified lr-MSM, and 51 of 92 (55%)
unqualified hr-MSM tested positive for syphilis. Anti-HBc reactiv-
ity was lowest in repeat donors (6/583 [1%]) and new donors (8/361
[2%]). It was significantly higher among MSM (P<.001), increas-
ing from qualified lr-MSM (15/197 [8%]), qualified hr-MSM
(17/183 [9%]), to unqualified lr-MSM (6/48 [13%]), to unqualified
hr-MSM (26/92 [26%]). An anti-HBs titer <200IU/L was found
in 0 of 583 repeat donors, 4 of 361 (1%) new donors, 5 of 197 (3%)
qualified lr-MSM, 8 of 183 (4%) qualified hr-MSM, 4 of 48 (8%)
unqualified lr-MSM, and 9 of 92 (10%) unqualified hr-MSM. One
qualified lr-MSM and 1 qualified hr-MSM had a chronic HBV
infection (HBsAg-positive). We found no recent class Ainfections
in repeat donors and (un)qualified lr-MSM. In qualified hr-MSM
we found 2 recent syphilis infections and 2 recent anti-HBc sero-
conversions. In unqualified hr-MSM we found 6 recent syphilis
infections and 1 recent anti-HBc seroconversion.
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4 • CID 2018:XX (XX XXXX) • van Bilsen etal
Class B Infections
Prevalence of antibody to HEV (anti-HEV) and to parvovirus
B19 (anti–parvovirus B19) was similar among repeat donors
and MSM, regardless of MSM group. It varied from 13% to
23% for anti-HEV and from 74% to 90% for anti–parvovirus
B19. The seroprevalence of human herpesviruses (HHVs) was
significantly higher among MSM compared to repeat donors
(P < .001 for all). CMV antibody reactivity varied from 68%
in qualified lr-MSM to 92% in unqualified hr-MSM, compared
to 38% in repeat donors. HSV-1/2 antibody reactivity varied
from 81% in qualified lr-MSM to 90% in unqualified hr-MSM,
compared to 46% in repeat donors. HHV-8 antibody reactiv-
ity varied from 39% in qualified lr-MSM to 65% in unqualified
lr-MSM, compared to 5% in repeat donors.
MSM With Low Sexual Risk Behavior
Additional analyses revealed no significant difference in
seroprevalence of class Ainfections, HEV, or parvovirus B19
between 3 groups of qualified lr-MSM (Table 1). MSM who
reported consistent condom use with casual partners had
a higher prevalence of CMV, HSV, and HHV-8 (P < .001,
P=.004, and P=.049, respectively), compared with MSM who
reported no anal intercourse or a monogamous relationship in
the precedingyear.
Sensitivity Analysis
Results did not change when all 35 MSM with missing risk
behavior data were classified as lr-MSM or hr-MSM. Likewise,
results did not change when all 38 MSM with missing qualifica-
tion data were classified as qualified or unqualified. Finally, our
results remained similar if using 2 alternative approaches for IP
calculation (Supplementary Data 2).
DISCUSSION
To our knowledge, this is the first study focusing on suitabil-
ity of MSM to donate blood, taking into account self-reported
sexual risk behavior linked to the seroprevalence of multiple
sexually transmitted and TTIs. None of the qualified lr-MSM
had acquired HIV, HBV, HCV, HTLV, or syphilis within the
Figure1. Flowchart of the study population of men who have sex with men (MSM), repeat male donors, and potential new male donors. We distinguished MSM with
low- and medium-to-high-risk sexual behavior from MSM who were qualified and unqualified to donate blood using Dutch donor deferral criteria other than male-to-male
sex. Abbreviations: ACS, Amsterdam Cohort Studies; DHQ, Donor Health Questionnaire; MSM, men who have sex with men.
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• CID 2018:XX (XX XXXX) • 5
Blood Donation byMSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HBV
repeat new qualified qualified unqualified unqualified
donors donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HIV
repeat new qualified qualified unqualified unqualified
donors donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HCV
repeat new qualified qualified unqualified unqualified
donors donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HTLV
repeat new qualified qualified unqualified unqualified
donors donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
syphilis
repeat new qualified qualified unqualified unqua lified
donors donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HEV
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
CMV
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HSV
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
Parvo B19
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
HHV-8
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
1
2
3
4
5
6
Median, IQR
Infecon pressure
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
0
10
20
30
40
50
60
70
80
90
100
Percentage, 95%-CI
Low infecon pressure
repeat qualified qualified unqualified unqualified
donors lr-MSM hr-MSM lr-MSM hr-MSM
Figure2. Infection pressure, proportion with low infection pressure, and antibody prevalence in repeated donors, new donors (class Aonly), qualified low-risk (lr) men who
have sex with men (MSM), qualified high-risk (hr) MSM, unqualified lr-MSM, and unqualified hr-MSM. Abbreviations: CI, confidence interval; CMV, cytomegalovirus; HBV,
hepatitis B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; HHV-8, human herpesvirus type 8; HIV, human immunodeficiency virus; hr-MSM, MSM with medium-to-high
sexual risk behavior; HSV, herpes simplex virus; HTLV, human T-cell lymphotropic virus; IQR, interquartile range; lr-MSM, MSM with low sexual risk behavior; MSM, men
who have sex with men; Parvo B19, parvovirus B19.
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6 • CID 2018:XX (XX XXXX) • van Bilsen etal
previous year and, except for HBV, the antibody prevalence of
these 5 infections were comparable to prevalence in new and
repeat male donors.
e anti-HBc prevalence among qualied lr-MSM was
higher than in donors, but two-thirds of these MSM had anti-
HBs titers >200 IU/L, making them eligible donors according
to the current donor guidelines on HBV in the Netherlands
[15]. One qualied lr-MSM who reported no male-to-male
sex within the preceding year had a preexisting chronic HBV
infection. is MSM complied with current donor eligibility
criteria in the Netherlands, and his HBV infection would have
been detected with routine donor screening. Qualied hr-MSM
had an increased seroprevalence of both HBV and syphilis com-
pared to donors and, importantly, 4 of 23 (17%) had acquired
these infections within the last year. As recent infections may
slip through routine donor screening as infectious “win-
dow-phase donations,” deferral of hr-MSM seems legitimate.
In the Netherlands, universal vaccination of newborns without
catch-up of adolescents was introduced in 2011 [16]. HBV vac-
cination is free of charge for MSM since 2002, and actively stim-
ulated using a targeted vaccination program [17]. Over time,
these preventive measures will result in a further decrease of
HBV transmission among all citizens [17–19].
e median IP in qualied lr-MSM and hr-MSM was sig-
nicantly higher than in repeat donors. For qualied lr-MSM,
this was due to an increased seroprevalence of HHVs (ie, CMV,
HSV, and HHV-8). ose who reported consistent condom
use with casual partners had a signicantly higher prevalence
of HHVs than MSM in a monogamous relationship and MSM
who had no anal intercourse in the preceding year. HHVs are
easily transmitted by close contact, and could be a marker
for increased sexual activity. Because CMV, HSV-1/2, and
HHV-8 are cell associated, universal leukodepletion consider-
ably reduces their risk of transmission via red blood cells and
platelets. eir infectious burden in plasma for transfusion or
fractionation is reduced using a combination of pathogen-inac-
tivating and virus-reducing procedures. Although donors in the
Netherlands are not screened for HHVs, it cannot be excluded
that the increased seroprevalence of CMV, HSV-1/2, and
HHV-8 observed in lr-MSM represents increased sexual risk
taking that might compromise blood safety. Further research is
needed on whether these and other potential laboratory mark-
ers are indeed relevant to maintaining blood safety.
The major strength of this study is that MSM were classified
based on detailed information on sexual risk behavior collected
in a prospective longitudinal cohort study. We used predefined
Table1. Age, Antibody Reactivity, and Infection Pressure of 583 Repeat Male Blood Donors and 197 Qualified Men Who Have Sex With Men With
Self-reported Low Sexual Risk Behavior
Characteristic
Repeat Male Blood
Donors
MSM With Low Sexual Risk Behavior
No Anal
Intercourse
Monogamous
Relationship
Consistent
Condom Use
PValuea
(n=583) (n=42) (n=48) (n=107)
Age, y, median (IQR) 42 (34–48) 44 (39–48) 39 (30–44) 42 (36–48) .014
Serology
Class Ainfections
HIV 0 (0) 0 (0) 0 (0) 0 (0) …
HBV (anti-HBc) 6 (1) 3 (7) 1 (2) 11 (10) .204
HBsAg 0 (0) 1 (1) 0 (0) 0 (0) .157
Anti-HBs >200 IU/L 6 (1) 2 (5) 1 (2) 7 (7) .502
HCV 0 (0) 0 (0) 0 (0) 0 (0) …
HT LV 0 (0) 0 (0) 0 (0) 0 (0) …
Syphilis 0 (0) 0 (0) 0 (0) 0 (0) …
Class B infections
HEV 116 (20) 5 (12) 11 (23) 13 (12) .183
Parvovirus B19 432 (74) 33 (79) 38 (79) 74 (69) .303
CMV 220 (38) 21 (50) 27 (56) 86 (80) <.001
HSV 267 (46) 30 (71) 34 (71) 96 (90) .004
HHV-8 30 (5) 16 (38) 12 (25) 49 (46) .049
Infection pressure
Median IP (IQR) 2 (1–2) 3 (2–3) 3 (2–3) 3 (2–4) .004
Low IP 443 (76) 19 (45) 47 (50) 33 (31) .047
Data are presented as No. (%) unless otherwise indicated.
Abbreviations: anti-HBc, antibodies to hepatitis B core antigen; anti-HBs, antibodies to hepatitis B surface antigen; CMV, cytomegalovirus; HBsAg, hepatitis B surface antigen; HBV, hepatitis
B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; HHV-8, human herpesvirus 8; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV, human T-cell lymphotropic virus;
IP, infection pressure; IQR, interquartile range; MSM, men who have sex with men.
aP value for comparing 3 groups of qualified MSM with low sexual risk behavior.
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• CID 2018:XX (XX XXXX) • 7
Blood Donation byMSM
criteria to distinguish between lr-MSM and hr-MSM, based on
sexual behavior associated with acquiring HIV infection [20–22].
The criteria could easily be incorporated in the DHQ and are
generally accepted and even suggested by MSM [23].
Our study has the following limitations. First, the study size
might have resulted in a low power for accurate estimates and
comparisons, in particular for low prevalent class Ainfections.
Second, the infection pressure calculation is arbitrary. Class
Ainfections were weighted double, because of their higher rel-
evance to blood safety. However, alternative approaches to cal-
culate IP did not substantially change our results. ird, ACS
participants might not represent the larger MSM population
living in the Netherlands. Due to its objectives and inclusion
criteria, ACS enrolls sexually active MSM and might underrep-
resent MSM with very low sexual risk behavior. is selection
bias might have led us to overestimate the IP among MSM. On
the other hand, all MSM from the ACS were oered HBV vac-
cination. is might not be representative for the larger MSM
population, leading to an underestimation of the IP. Fourth,
antibody reactivity was used as a marker for lifetime sexual
behavior and does not solely represent sexual behavior within
the previous year. As sexual behavior uctuates over life [24],
the antibody reactivity in lr-MSM could result from beha-
vior that has been discontinued. To partially correct for this,
we distinguished between past and recent class Ainfections.
Fih, repeat donors do not represent the general population, as
they are selected based on their low risk of TTIs. Dutch donors
have a 6- to 60-fold lower TTI prevalence and incidence com-
pared to the general population [14]. Moreover, repeat donors
had been screened for HIV, HBV, HCV, and syphilis at every
donation visit. If found positive, they would have been perma-
nently deferred. Hence, by denition, class Ainfections among
repeat donors would be recent infections among a selected
group without a history of class Ainfections. New donors were
included as a second comparison group. ey have not previ-
ously been tested for class Ainfections and therefore are less
likely to be subject to selection bias. Indeed the seroprevalence
of HBV, HCV, and syphilis in new donors is higher than in
repeat donors and closer to that of qualied lr-MSM.
CONCLUSIONS
Our study shows that MSM with low sexual risk behavior who
did not report any of the criteria for permanent donor deferral in
the Netherlands had no recent HIV, HBV, HCV, HTLV, or syph-
ilis infections. Their seroprevalence of these infections was sim-
ilar to new and repeat donors. Antibody prevalence to HHVs in
lr-MSM was significantly higher than in repeat donors, but the
epidemiological significance of this finding to recipient safety
is unclear. Our results suggest that hr-MSM pose an increased
threat to blood safety, as recently acquired HBV and syphilis
infections were found in this group. Our results justify further
study of the suitability of lr-MSM to donate blood, with addi-
tional focus on MSM compliance with guidelines and self-with-
drawal, especially considering the high proportion of MSM
with a moderate-to-high intention to donate.
SupplementaryData
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benet the reader, the posted
materials are not copyedited and are the sole responsibility of the authors,
so questions or comments should be addressed to the corresponding author.
Notes
Author contributions. T.J. W.L., K.H., H.L. Z., and M.P.are respon-
sible for the study design. M.F. S.L.and M.P.supervised data collection
for MSM, and E.S.and T.J. W.L.supervised data collection for donors. T.J.
W.L.was responsible for laboratory testing. W.P. H.B.performed the statis-
tical analysis under supervision of A.M.and M.P.. All authors contributed
to the interpretation of the results, writing of the manuscript, and providing
intellectual feedback. All authors have seen and approved the nal submit-
ted version of the manuscript.
Acknowledgments. e authors gratefully acknowledge the
Amsterdam Cohort Studies (ACS) on HIV Infection and AIDS, a collab-
oration between the Public Health Service of Amsterdam, the Academic
Medical Center of the University of Amsterdam, the Sanquin Blood
Supply Foundation, Medical Center Jan van Goyen, and the HIV Focus
Center of the DC-Clinics. It is part of the Netherlands HIV Monitoring
Foundation and nancially supported by the Center for Infectious Disease
Control of the Netherlands National Institute for Public Health and the
Environment. e authors thank all ACS participants and blood donors
for their contribution. On behalf of the authors, we also thank Alexandra
Kovaleva and the research nurses of ACS for their contributions to data
collection, Udi Davidovich for his valuable input on study design and
interpretation of results, and Anders Boyd for his statistical advice and
input.
Financial support. is study was nanced by the Research and
Development Foundation of the Public Health Service of Amsterdam and a
Product and Process Development Cellular Products grant (PPOC 15-04)
of Sanquin.
Potential conicts of interest. All authors: No reported conicts of
interest. All authors have submitted the ICMJE Form for Disclosure of
Potential Conicts of Interest. Conicts that the editors consider relevant to
the content of the manuscript have been disclosed.
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