Wangetal. AIDS Research and Therapy (2022) 19:28
Evidence andimplication ofinterventions
acrossvarious socioecological levels
toaddress pre-exposure prophylaxis uptake
andadherence amongmen who have sex
withmen intheUnited States: asystematic
Ying Wang1, Jason W. Mitchell2, Chen Zhang3 and Yu Liu1,4*
Background: Pre-exposure prophylaxis (PrEP) represents a proven biomedical strategy to prevent HIV transmissions
among men who have sex with men (MSM) in the United States (US). Despite the design and implementation of
various PrEP-focus interventions in the US, aggregated evidence for enhancing PrEP uptake and adherence is lacking.
The objective of this systematic review is to synthesize and evaluate interventions aimed to improve PrEP uptake and
adherence among MSM in the US, and identify gaps with opportunities to inform the design and implementation of
future PrEP interventions for these priority populations.
Methods: We followed the PRISMA guidelines and conducted a systematic review of articles (published by Novem-
ber 28, 2021) with a focus on PrEP-related interventions by searching multiple databases (PubMed, MEDLINE, Web
of Science and PsycINFO). Details of PrEP interventions were characterized based on their socioecological level(s),
implementation modalities, and stage(s) of PrEP cascade continuum.
Results: Among the 1363 articles retrieved from multiple databases, 42 interventions identiﬁed from 47 publica-
tions met the inclusion criteria for this review. Most individual-level interventions were delivered via text messages
and/or apps and incorporated personalized elements to tailor the intervention content on participants’ demographic
characteristics or HIV risk behaviors. Interpersonal-level interventions often employed peer mentors or social network
strategies to enhance PrEP adoption among MSM of minority race. However, few interventions were implemented at
the community-, healthcare/institution- or multiple levels.
Conclusions: Interventions that incorporate multiple socioecological levels hold promise to facilitate PrEP adoption
and adherence among MSM in the US given their acceptability, feasibility, eﬃcacy and eﬀectiveness. Future PrEP inter-
ventions that simultaneously address PrEP-related barriers/facilitators across multiple socioecological levels should be
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AIDS Research and Therapy
4 Division of Epidemiology, Department of Public Health Sciences, University
of Rochester Medical Center, 256 Crittenden Blvd, Ste. 3305, Rochester, NY
Full list of author information is available at the end of the article
Page 2 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
Men who have sex with men (MSM) experience a dis-
proportionate burden of HIV in the US, accounting for
approximately 70% of the 36 thousand new HIV diagno-
ses in 2019 . Particularly, MSM of color (e.g., Black and
Hispanic/Latino MSM) continue to be the priority popu-
lations most aﬀected by HIV, representing nearly half of
the new infections among all MSM in the US [1–4]. e
challenges of HIV prevention in MSM are further com-
plicated by their low perception of HIV risk, the lack of
sustainable use of pre-exposure prophylaxis (PrEP), low
HIV testing uptake, and high prevalence of behaviors that
increase acquisition/transmission of HIV (e.g., condom-
less receptive/insertive anal sex, multiple anal sex part-
ners, and exchange of sex for money/drugs) [5–7].
Currently approved medications for PrEP, a prescrip-
tion medicine to prevent HIV infections, include Truvada
(for all people at risk for HIV) and Descovy (for peo-
ple at risk for HIV through anal sex and less impact on
kidney and bone health) . When taken as prescribed,
daily oral PrEP has been shown to lower the risk of HIV
infection from sex by > 99% and from injection drug use
by > 74% [9–12]. Mathematical models showed that HIV
infections among people who were at high risk for HIV
while adhering to PrEP had decreased by 18% from 2016
to 2020 . erefore, high-impact prevention interven-
tions to enhance PrEP uptake among MSM provide one
eﬀective strategy to end the HIV epidemic in the US [14,
PrEP care continuum is usually used to evaluate
interventions for PrEP, including (1) awareness (knowl-
edge about PrEP), (2) willingness/intention (likelihood
of initiating PrEP), (3) access (linking PrEP candidates
to healthcare system), (4) uptake (PrEP initiation),
and (5) adherence (adherence to PrEP and retention
in PrEP care) . Despite the increased availability
and proven eﬃcacy in preventing new HIV infections,
the level of engagement along the PrEP care contin-
uum remains low among MSM in the US [5, 16–18].
For example, pooled analyses showed that only 13.9%
of MSM have reported ever using PrEP in their life-
time (95% conﬁdence interval (95% CI): 8.8–21.1) .
Numerous observational studies with MSM in the US
have revealed important barriers across multiple socio-
ecological levels that may aﬀect the uptake/adherence
of PrEP, including individual—(e.g., perception of low
HIV risk, insuﬃcient PrEP knowledge and concerns
over side eﬀects) [19–21], interpersonal—(e.g., lack of
parent/peer support) [20–22], healthcare system—(e.g.,
high cost and low PrEP care quality) [5, 19, 20] and
social-cultural—(e.g., stigma, discrimination and medi-
cal mistrust) levels [5, 19–21, 23].
Since 2017, there has been an increasing number of
interventions to enhance the engagement in PrEP care
continuum among MSM by modifying their individ-
ual health behaviors or social networks. For example,
PrEPmate was one of the early mobile health interven-
tions that utilized daily text messages to remind young
MSM (YMSM) of PrEP medication . Interventions
that leveraged peer inﬂuence to improve intentions and
willingness to use PrEP among MSM of color were also
reported in recent years [25–27]. While these interven-
tions employed novel strategies (e.g., mobile health and
social network) and showed eﬃcacy in improving PrEP
care continuum in MSM, some limitations were also
acknowledged by the authors, including sustainability
post intervention period, discrepancy between inter-
vention content and participants’ time-varying inter-
vention needs, and lack of parent/school engagement in
PrEP interventions [24–26].
Despite the design and implementation of various
PrEP interventions for MSM in the US, there is a need
to systematically summarize the practical/theoreti-
cal components, modalities, strengths, and limitations
of these PrEP-focused HIV prevention interventions
for MSM. Aggregated evidence presented on diﬀerent
socioecological levels (e.g., individual, interpersonal,
community and healthcare/institution levels)—via a
systematic review—enables us to compare interven-
tions across socioecological levels (e.g., acceptability,
feasibility or eﬃcacy), informs HIV prevention sci-
entists about successful intervention strategies that
modify physical or social environments rather than
changing only individual health behaviors, as well as
reveals ways to improve current and former PrEP inter-
ventions. We conducted a systematic review of inter-
vention studies that aimed to improve one or more
aspects of the PrEP care continuum among MSM in the
US, by summarizing included studies and their socioec-
ological mechanistic levels, implementation modalities
(peer/couple-based, technology-assisted, social net-
work, etc.), and which aspects of the PrEP cascade (e.g.,
initiation, uptake, and adherence) they targeted.
enhanced with a focus to tackle contextual and structural barriers (e.g., social determinants of health, stigma or medi-
cal mistrust) at the community- and healthcare/institution-level to eﬀectively promote PrEP use for MSM of color.
Keywords: Pre-exposure prophylaxis, Intervention, Men who have sex with men, Systematic review, United States
Page 3 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
Literature search strategy
is systematic review was conducted by searching
articles via multiple databases (PubMed, MEDLINE,
Web of Science and PsycINFO) published by November
28, 2021, following the PRISMA guidelines . e
ﬁnal search terms included: (“gay” OR “men who have
sex with men” OR “bisexual” OR “homosexual” OR
“homosexuality” OR “same-gender-loving” OR “sexual
minority”) AND (“PrEP” OR “pre-exposure prophy-
laxis” OR “preexposure prophylaxis”) AND (“interven-
tion” OR “trial” OR “experiment” OR “randomized” OR
Studies were included in this systematic review if they
met the following criteria: (1) published journal articles
excluding abstracts, conference proceedings, reviews,
meta-analyses, editorials or commentaries; (2) con-
ducted in the US; (3) the current and/or the parent
study was based on an experimental or quasi-experi-
mental design (e.g., randomized controlled trial (RCT),
randomized interventional studies, and pre-post trial)
to evaluate the eﬃcacy or eﬀectiveness of a PrEP inter-
vention; (4) reported at least one PrEP care continuum
outcome (e.g., awareness, willingness, intention, uptake
and adherence); (5) conducted among males who self-
identiﬁed as gay, bisexual, or reported having sex with
men within a past time window; and (6) published in
To achieve our goal of comprehensively summarizing
PrEP interventions for MSM in the US, we also included
the following studies for potential evaluation: (1) studies
conducted among MSM and other priority populations
(e.g., transgender women); (2) studies that used an exper-
imental design to evaluate the acceptability, feasibility,
cost-eﬀectiveness of a PrEP intervention with reporting
PrEP-related outcomes; (3) studies using an non-experi-
mental design (e.g., qualitative or cross-sectional study)
to assess the acceptability, feasibility or cost-eﬀectiveness
of an eligible intervention if details about its implementa-
tion to evaluate eﬃcacy/eﬀectiveness could be retrieved
from their published parent trials by checking the refer-
ence lists; (4) we also included protocols that elaborated
the design and implementation to supplement our sum-
mary of the PrEP interventions. We excluded studies that
used a composite measure of HIV risk with PrEP uptake
as one of the risk calculation criteria if PrEP uptake was
not explicitly reported. We also excluded papers that
described the development/adaptation of eligible inter-
ventions without reporting interested PrEP-related
Study screening anddata extraction
Titles and abstracts of all identiﬁed records were ﬁrst
screened for duplicate removal and relevancy by two
independent reviewers (Y.W. and Y.L.). e full text
review and data extraction were then conducted indepen-
dently by one author (Y.W.), and further cross-checked
by the other author (Y.L.) for accuracy. Disagreements
were resolved by consensus-based discussion. e fol-
lowing information was extracted from eligible studies:
study location/setting, study/recruitment period, study
design, recruitment strategy, participant characteristics,
intervention content, theoretical/conceptual framework,
control group, sample size and retention, study out-
come measures (e.g., PrEP care continuum outcomes)
and major ﬁndings from the interventions (e.g., eﬃcacy,
eﬀectiveness, feasibility and acceptability).
We categorized all interventions into diﬀerent socio-
ecological levels based on the primary barriers the inter-
ventions aimed to address. e original socioecological
model to guide HIV studies was composed of four layers:
individual, interpersonal, community and structural level
. We replaced structural level with healthcare level
(i.e., interventions implemented in healthcare settings)
since we did not identify interventions that may impact
laws or policies. We additionally modiﬁed this model by
adding a layer of multiple levels to describe interventions
that address PrEP-related barriers/facilitators across
multiple socioecological levels.
A total of 1363 articles were found through the initial
search of multiple databases. After removing duplicates
and ineligible articles through title/abstract screening,
66 papers were further assessed via full-text review, with
47 papers representing 42 interventions retained for the
ﬁnal systematic review. Of the included studies, twenty-
three papers evaluated the acceptability (n = 8), feasibility
(n = 8), eﬃcacy (n = 18) or eﬀectiveness (n = 1) of inter-
ventions aimed at improving PrEP uptake and adherence
among MSM in the US. Twenty-four of the 47 articles
described the protocols for the design and implementa-
tion of relevant interventions. Study selection process is
shown in Fig.1.
Forty-two interventions were categorized into 5 socio-
ecological levels and characteristics of interventions
on each level are presented in Additional ﬁle1: Tables
S1–S5, respectively. PrEP interventions for MSM were
reported to implement in the US South (Florida, Geor-
gia, Texas, Maryland, Mississippi, North Carolina and
Page 4 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
D.C.) [30–40], Northeast (Pennsylvania, New York, Mas-
sachusetts and Rhode Island) [27, 31–33, 36, 38, 41–49],
Midwest (Illinois, Michigan, and Wisconsin) [24–26,
32, 33, 36, 47, 50–52], West (California) [51, 53–58]
and nationwide [59–63]. irty-seven of the 42 studies
focused solely on MSM [24–27, 30–34, 36–41, 43–47,
49–54, 56, 58–72], with some targeting Black, Hispanic/
Latino MSM or MSM younger than 34 years old [24–27,
30–34, 36–40, 44–46, 49, 50, 52, 56, 58, 60–63, 70]. Five
studies were conducted among MSM and other prior-
ity populations(e.g., transgender women or heterosex-
ual men) [35, 42, 48, 55, 57]. A RCT design was used to
evaluate 37 interventions on their eﬀect on PrEP-related
outcomes [24, 25, 27, 30–42, 44–48, 50, 52–56, 58–63,
66–72], whereas 5 interventions were evaluated using a
quasi-experimental design [26, 43, 49, 51, 57] and 4 via a
pretest-posttest design [26, 49, 51, 57].
Study outcomes acrosspre‑exposure prophylaxis care
Most interventions were evaluated by PrEP-related
outcomes across the PrEP care continuum with PrEP
uptake (n = 29) and adherence (n = 24) most commonly
reported. Awareness of PrEP was measured by partici-
pants’ knowledge about PrEP including medication pur-
pose, side eﬀects and self-eﬃcacy [25–27, 31, 33, 39, 40,
43–45, 49, 56, 60, 63, 70]. PrEP willingness/intention
focused on participants’ attitudes towards PrEP use such
as their likelihood of initiating PrEP across various con-
ditions or during a future time window (e.g., within the
next 3 or 6 months) [25–27, 31, 33, 34, 39, 44, 57, 59, 60,
63, 70]. Access to PrEP was referred to participants’ link-
age to healthcare system (e.g., scheduling or attending
an appointment for PrEP consultation) [25, 27, 33–35,
39, 52, 58, 69–71]. PrEP uptake was measured by self-
reported PrEP initiation or a recipient of a prescription
for PrEP [25, 30, 31, 34–36, 38, 39, 43–46, 52, 54, 55, 57,
58, 60, 69–72]. Adherence to PrEP utilized both behavio-
ral (e.g., self-reported retention in PrEP care or number
of doses missed in the past 30 days) [30–33, 36, 40, 46,
48–51, 58, 60, 73] or biological measurements (e.g., PrEP
concentration in dried blood spots) [24, 32, 33, 37, 40–42,
53, 72]. Outcomes out of the PrEP care continuum were
also reported in a few studies, including descriptive and
subjective PrEP norms, PrEP-related stigma and barriers
to PrEP [25–27].
Fig. 1 Flowchart of study selection and inclusion procedure
Page 5 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
Intervention strategies andndings
Building on the Social-ecological Model and the char-
acteristics of the reviewed interventions , we
categorized 42 interventions into individual-, inter-
personal-, community-, healthcare/institution-level,
and multilevel interventions. e vast majority of these
interventions were delivered at the individual or inter-
personal level. e sub-categories under individual-
level interventions were not mutually exclusive (e.g., a
technology-assisted intervention may include personal-
ized/individualized elements). Hence, the intervention
types/levels presented below were used to provide the
audience with examples of various interventions.
PrEP regimen interventions
PrEPare was one of the initial intervention trials that
tested the eﬀect of daily tablets combined with a behav-
ioral intervention on adherence to PrEP in YMSM
compared to placebo pill control combined with the
behavioral intervention and behavioral intervention
alone . Another trial implemented in New York City
evaluated 3 diﬀerent dosing regimens of PrEP, 1 tablet
twice weekly with a post-sex dose, 1 tablet before and
after sex and 1 tablet daily . Both interventions sug-
gest that daily oral PrEP was associated with a high
level of medication adherence compared to other dos-
ing recommendations [42, 50].
In recent years, text messages have become one of the
most indispensable components used in PrEP interven-
tions [33, 52]. For example, participants in LifeSteps
received text messages on a weekly basis as a motiva-
tional reminder to enhance PrEP adherence . Using
the Behavioral eories and Information-Motivation-
Behavioral Skills (IMB) framework, bidirectional text
message interventions were implemented to boost
communication between participants and research
team [24, 52, 53]. For example, daily pill reminder mes-
sages were sent to participants at a personally selected
time, with study staﬀ providing assistance to partici-
pants who did not respond to the message or reported
any diﬃculty with PrEP use [24, 51, 53]. Partner Ser-
vices PrEP study also used text messages to deliver
booster sessions to follow up on participants’ experi-
ences getting linked to PrEP medication . Overall,
text message interventions based on mobile technol-
ogy were found to be feasible, acceptable and eﬃca-
cious when the messages were personalized and able to
address speciﬁc needs of the target population [24, 51,
e development of app-based interventions address-
ing individual level barriers/facilitators has proliferated
since 2017. Most apps were grounded in health behav-
ior change theories, such as Social Cognitive eory
(SCT), Social Learning eory and the IMB model [30,
32, 40, 45, 47, 61, 70]. e apps compiled relevant infor-
mation that may inﬂuence PrEP use (e.g., education of
correct HIV risk perception, medication eﬃcacy, self-
eﬃcacy and social norms) and integrated supports from
local PrEP providers to improve participants’ awareness
of PrEP and facilitate linkage to PrEP care [30, 37, 45,
47, 61, 62, 70]. Other key features that might facilitate
participants’ adherence to PrEP included medication
reminder, graphical tracking of medication adherence
and day-to-day strategies to counter relevant barriers
(e.g., PrEP stigma) [32, 49]. App-based interventions
were found to be acceptable and feasible [57, 64, 65],
but their eﬃcacy remains unclear as most studies are
still ongoing [32, 37, 47, 61, 62, 70, 72].
Of particular note, game-based interventions have
been gaining popularity in recent years. For example,
Viral Combat is one of the early apps that used gamiﬁca-
tion to increase adherence to PrEP among YMSM. In this
game, players gain points by engaging with healthcare
providers (HCPs), initiating and adhering to the PrEP
medication . is game demonstrated that interven-
tion participants were 3.75 times more likely to engage in
optimal PrEP dosing compared to those who received a
non-PrEP related mobile game (95% CI 1.20–11.77).
Other technology-based interventions at the individual
level included interventional videos or messages deliv-
ered through open network social media platforms/web-
sites (e.g., Facebook, Instagram, Reddit, Twitter) [44, 59,
63]. For example, van den Berg etal. examined whether
SCT-based and culturally congruent social media mes-
sages would increase PrEP knowledge among Black and
Hispanic MSM . is trial is ongoing and the results
have not yet been reported.
Some technology-assisted interventions often incorpo-
rate personalized/individualized elements by custom-
izing the intervention content based on participants’
demographic characteristics or HIV risk behaviors [31,
44, 47, 49, 62]. For example, M-Cubed intervention tai-
lored HIV prevention messages to participants’ self-
reported HIV status and level of HIV risk . In an
intervention for MSM of color, cognitive interviewing
was used to develop HIV prevention information tailored
to participants’ serostatus and culture . Most person-
alized interventions are ongoing and have not reported
their results [31, 44, 47, 62].
Page 6 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
Other individual‑level intervention strategies
e PrEPARE2 intervention tested whether provision of
objective HIV risk score to MSM had a positive impact
on their uptake of PrEP . e score was generated
from a mathematic model that considered both HIV risk
behavior (e.g., condomless anal intercourse) and bio-
logical outcomes [e.g., sexually transmitted infections
(STIs)]. It is reported that PrEPARE2 did not increase
PrEP initiation among MSM (11% vs. 10%, p > 0.99) .
Overall peer‑based interventions
Most peer-based interventions utilized peer interven-
tionists to enhance engagement of minority MSM in the
PrEP care continuum. In an ongoing peer-navigation
intervention, Spanish–English bilingual peer lay navi-
gators delivered PrEP-focused educational modules to
Latino MSM . In a diﬀerent intervention that utilized
enhanced PrEP adherence support, peer navigators led
both in-person and online groups to provide adherence
support to Black MSM . However, favorable changes
in self-reported PrEP adherence were not observed for
this enhanced adherence intervention .
We also observed that peer-based interventions often
incorporated personalized elements [34, 38, 55, 56]. In a
culturally-tailored counseling intervention, Black MSM
interventionists helped participants identify and address
their barriers to PrEP initiation (e.g., health insurance,
mental health violence, alcohol and substance abuse)
based on their prevention needs, and referred them to
appropriate prevention resources . is counseling
intervention demonstrated preliminary eﬃcacy where
24% of participants in the intervention group initiated
PrEP compared to no one in the control group (p = 0.02)
Motivational interviewing (MI) was another common
strategy applied in peer-based interventions. Peer men-
tors would use MI to help MSM resolve their ambiva-
lence about behavioral change as they moved through
the diﬀerent stages of change (e.g., contemplation, deter-
mination and action) [38, 55, 56]. In an ongoing coach-
based, mobile-enhanced intervention, participants who
reported barriers to telephonic engagement in HIV pre-
vention services would be connected with peer coaches,
who would empathize with them and assist by exploring
alternative means to help retain them in the study .
We identiﬁed one young male couple-based interven-
tion, We Prevent . Guided by relationship-oriented
IMB model, We Prevent aimed to enhance MSM-spe-
ciﬁc sexual health knowledge (e.g., risk within dyads),
motivation (e.g., peer norms towards HIV prevention in
relationships) and HIV risk-reduction skills (e.g., cou-
ples HIV testing and counseling and PrEP) via two ses-
sions delivered to male couples. e intervention also
employed MI techniques to teach identiﬁcation of
unhealthy relationships and communication strategies
with partners to help them prepare for engaging in HIV
prevention services as a couple . is couples-based
intervention is ongoing and its eﬃcacy is unknown.
Social network interventions
Based on the framework of IMB and SCT, three social
network interventions, E-PrEP, PrEP Chicago and one
conducted in Wisconsin, were developed for young Black
or Latino MSM [25–27]. ese interventions focused on
improving participants’ knowledge about PrEP and sub-
sequent PrEP initiation, and leveraged peer inﬂuence to
scale up PrEP uptake in peers’ social networks. Partici-
pants in the E-PrEP intervention posted targeted materi-
als on social media to provide PrEP education to peers
in their existing online networks . e other two peer
change agent-based interventions emphasized training
of communication skills and conversational strategies
to ensure peer change agents could advocate PrEP use
eﬀectively. Peer change agents learned how to address
their friends’ concerns about PrEP (e.g., sigma, miscon-
ception, eﬀectiveness and side eﬀects) while also engag-
ing with them to help facilitate development of positive
attitudes toward PrEP [25, 26]. Social network interven-
tions exhibited high acceptability and eﬃcacy in improv-
ing PrEP knowledge, attitudes, and self-eﬃcacy among
young minority MSM [26, 68].
An active PrEP patient navigation was one of the few
interventions that leveraged community engagement
in HIV prevention programs . Guided by the model
of community-based case management that focused on
utilization of support and resources in the community,
patient navigators assisted participants with overcoming
barriers to PrEP linkage and identifying available sources
of support in the community . For example, if partici-
pants reported administrative costs (e.g., notary services)
as a barrier to PrEP initiation, patient navigators would
then provide them with information on related commu-
nity services free of charge. e community-level inter-
vention showed preliminary eﬃcacy to facilitate PrEP
initiation, yet no signiﬁcant diﬀerences existed between
the intervention and control groups .
Interventions at the healthcare/institution level usually
involved HCP for PrEP promotion in various health-
care settings. In most healthcare-level interventions,
Page 7 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
HCPs (e.g., nurses, STI clinic counselors) provided par-
ticipants with information on PrEP access, used MI to
encourage PrEP initiation, or taught behavioral skills to
address PrEP-related barriers (e.g., PrEP stigma coping)
[36, 41, 43, 69]. Life-Steps for PrEP and one brief behav-
ioral intervention additionally oﬀered booster sessions to
construct/reﬁne medication adherence plans and moni-
tor participants’ long-term adherence to PrEP [41, 69].
Healthcare-level interventions were found to be eﬃca-
cious for improving PrEP awareness, PrEP appointment
scheduling, and PrEP initiation among MSM [43, 69].
However, signiﬁcant diﬀerences for PrEP adherence, via
measurement by an electronic pill storage device, were
not observed in the Life-Steps for PrEP intervention .
Interventions that address PrEP determinants across
multiple socioecological levels represent an important
interventional mechanism to eﬀectively promote PrEP
use among MSM [31, 57]. One of the few examples was
Get Connected, a web app-based intervention guided by
Integrated Behavioral Model and Self-Determination
eory, that combined both individual- and healthcare-
level strategies to help YMSM overcome multiple bar-
riers to PrEP care . At the individual level, the app
delivered personalized educational materials to partici-
pants to increase their awareness of HIV risk and self-
eﬃcacy for HIV prevention. At the healthcare/institution
level, participants were asked to rate the clinic where
they got tested for HIV or received PrEP evaluation. e
assessment used a composite measure which took into
account the clinical environment, service quality, pri-
vacy/conﬁdentiality, perceived provider competency,
etc. Participants’ evaluations were sent to sites to help
them understand and improve their performance that
may beneﬁt their future PrEP clients . is app is still
being tested and the results have not been reported.
We Are Family represents another multilevel interven-
tion conducted in San Francisco . At the individual
level, information on HIV prevention and local preven-
tion resources were delivered to participants through
in-person group sessions and the We Are Family app.
Participants were allowed to support and connect with
each other by sharing their stories of battling HIV-related
stigma. e research team also hosted or sponsored
community-level events such as prevention balls, game
nights and holiday parties to leverage community norms
to facilitate PrEP uptake in MSM. At the healthcare level,
a healthcare provider worked with the community to
provide HIV prevention services including HIV testing
or PrEP referral. is multilevel intervention was found
to be acceptable, feasible, and demonstrated preliminary
eﬃcacy in facilitating PrEP intention, initiation and
adherence among MSM .
e present systematic review provides a concise,
informative summary of what PrEP-related interventions
have occurred with MSM in the US. Most individual-
level PrEP interventions were technology-assisted and
delivered via messaging platforms and/or apps. Com-
pared with traditional venue-based interventions, tech-
nologically delivered PrEP interventions are convenient,
cost-eﬀective, and may help overcome system-level barri-
ers to PrEP care (e.g., transportation to clinics and incon-
venient clinic locations and hours) [74, 75]. In addition,
app-based interventions included in this review provided
extensive information on PrEP, ranging from medica-
tion eﬀectiveness, side eﬀects, self-eﬃcacy to local PrEP
resources—all aimed to improve participants’ aware-
ness of PrEP and help them build behavioral skills to
use PrEP [30, 32, 45, 47, 61, 70]. Some of the app-based
interventions included interactive features (e.g., quiz-
zes, exercises, discussions and games) to facilitate par-
ticipants’ continued use of the app (i.e., engagement) [32,
57, 61]. In contrast, text message interventions contained
fewer interactive features. One key strength of text mes-
sage interventions centered on them requiring fewer
resources for development and pilot testing (vs. apps).
In general, text message interventions were found to be
high acceptable by MSM [24, 48, 51, 53]. Further, partici-
pants could tailor for when and how often text messages
would be sent to accommodate their schedules for daily
PrEP intake [24, 51, 53]. Bidirectional messages may pro-
vide researchers with opportunities to better understand
participants’ medication adherence patterns and identify
when to provide assistance when necessary [24, 51, 53].
ese ﬁndings suggest text messaging interventions have
the potential to retain MSM in PrEP care.
It is also important to acknowledge the gaps in current
technology-assisted interventions. Development of apps
and platforms for interventions remain a barrier [51, 65].
Commonly reported issues regarding app design and
functions included lack of diversity in the presentation
of educational information, inability to link social media
proﬁles, lack of common functions (e.g., customizable
reminders), and technical glitches (e.g., slow responsive-
ness and app crashing) [30, 45, 51]. erefore, formative
studies to learn participants’ preference regarding the app
design are necessary to ensure the successful implemen-
tation of technology-based interventions. In addition,
there might be a mismatch between intervention content
and time-evolving prevention needs of MSM [24, 51].
For example, some visual/textual components used in an
intervention might only oﬀer introductory information
Page 8 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
skills to facilitate PrEP initiation, which would be less
useful to experienced PrEP users with challenges with
PrEP adherence . To meet the evolving needs of
MSM, future PrEP interventions could be designed and
tailored to better align with the PrEP continuum and
men’s ongoing needs.
We observed that approximately 60% of the existing
PrEP interventions were designed for YMSM; and more
than 70% of these interventions relied on technology to
facilitate PrEP uptake. is ﬁnding aligns with the ever-
growing eﬀorts in recent years to address the elevated
HIV epidemic among YMSM in the US . Given the low
rates of PrEP use among YMSM and preference of inter-
vention modality supported by technology (e.g., social
media, networking apps, internet) [76, 77], technology-
assisted interventional components may bode well in
future PrEP interventions to enhance the PrEP care con-
tinuum among YMSM [24, 49, 52, 66].
Several interpersonal-level PrEP interventions designed
and implemented among YMSM (e.g., peer-deliver/
navigation, couple-based, social network-based inter-
ventions) met inclusion criteria for the present review.
However, interpersonal interventions that involve par-
ent or school educators to promote PrEP among YMSM
are notably missing from the current review. Substantial
evidence indicates parent’s low level of PrEP awareness,
perceived HIV and LGBTQ+ related stigma and nega-
tive reaction to PrEP, along with adolescents’ poor self-
eﬃcacy to communicate with parents about PrEP and/
or sexual orientation were all reported barriers to PrEP
use among YMSM [22, 78, 79]. Interventions that address
parental negative attitudes towards PrEP and sexuality,
and that also promote parent-adolescent communication
may hold promise to enhance PrEP uptake and adher-
ence among YMSM. None of the included interventions
were implemented in school settings or educational
agencies. As adolescents and YMSM may spend a major-
ity of their day at school, the development and imple-
mentation of contextually appropriate interventions at
schools, by involving trusted school-based peers/counse-
lors, may oﬀer unique opportunities to provide education
about PrEP and HIV prevention among these priority
Black and Hispanic/Latino MSM (i.e., MSM of color)
were also priority populations in the included PrEP
interventions, given their heightened HIV burden and
low rates of PrEP uptake [2, 3, 80, 81]. Findings from the
present review revealed that some of the most important
strategies in PrEP interventions for MSM of color was
the utilization of peer inﬂuence, which led to increased
cultural congruence, reduced PrEP/HIV-related stigma,
facilitated trust/access to PrEP care, and motivated con-
formity to peer norms/behaviors (i.e., social comparison)
to promote PrEP initiation/adherence [25–27, 34, 38, 48,
However, challenges remain for PrEP interventions for
MSM of color. First, MSM of color may be less likely to
participate in online HIV interventions given the racial/
ethnic disparities in the use of technology for health-
related purposes [82, 83]. For example, almost all Black
MSM completed the face-to-face session in Partner Ser-
vices PrEP study, while only a limited number of partici-
pants completed the booster session delivered via mobile
phone . Second, our aggregated evidence reﬂects the
lack of interventions to tackle community-level determi-
nants of PrEP care for MSM of color. Community-level
interventions that address broader contextual and struc-
tural issues by improving social determinants of health
(e.g., neighborhood environment, housing and food
insecurity) should be further strengthened [48, 84]. Last,
we identiﬁed only one intervention, Get Connected, that
overcame system- and structural-level barriers to PrEP
(e.g., stigma and medical mistrust) by providing HIV care
that is sensitive and inclusive to MSM of color. Inter-
ventions delivered to HCPs to enhance clinical experi-
ences of MSM of color are still missing from the current
We identiﬁed four interventions implemented at
the healthcare/institution level. All these interven-
tions involved educational modules delivered by HCPs
in HIV/STI clinics [36, 41, 43, 69]. One of the gaps in
the healthcare/institution-level interventions is the
lack of follow-up for long-term adherence to PrEP.
We observed improvement in behaviors that align
with the earlier stages of the PrEP continuum (e.g.,
increased PrEP awareness, scheduling and attend-
ing a PrEP appointment, and initiating PrEP care) [43,
69], but signiﬁcant diﬀerences were not observed for
long-term adherence to PrEP . Current models of
care in HIV/STI clinics primarily provide STI and HIV
testing services and are not well suited for transition-
ing to a longitudinal model of HIV prevention/care
due to the absence of protocols to guide clinical prac-
tice and low capacity of trained HCPs to provide PrEP
care . One potential solution is to provide training
to PrEP counselors, who would then be responsible for
monitoring PrEP use among those who have initiated
the medication and providing follow-up counseling
services. Another gap is the lack of culturally trained
primary healthcare providers (PCPs) with specialty in
HIV/STI prevention/care for sexual and gender minor-
ity populations. Although HIV/STI clinics are ideal
settings to reach populations who are at elevated risk
for HIV infection , PCPs as the ﬁrst point of con-
tact into healthcare have a unique opportunity to reach
the majority of patients who are less aware of PrEP and
Page 9 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
may be in need of this preventative medication. For
example, evidence from an HIV prevention program
in Washington State showed a pronounced increase in
uptake of HIV prevention services (e.g., HIV testing)
among MSM who received healthcare from provid-
ers that were not from HIV/STI clinics, suggesting the
great potential of the entire healthcare system rather
than only HIV/STI care providers in promoting uptake
of HIV prevention services . Additionally, the pre-
scription of PrEP in primary healthcare settings, where
the primary purpose is not HIV prevention and care,
may have the potential to reduce stigma surrounding
HIV among MSM and thereby may help promote PrEP
acceptance . However, barriers such as insuﬃcient
PrEP knowledge and lack of skills/motivation to discuss
PrEP with MSM clients must be addressed among PCPs
before eﬀective structural/institution interventions can
be implemented [87–89].
Our study is among the few that have systematically
summarized and evaluated PrEP interventions for
MSM in the US to inform the design and implemen-
tation of future interventions. ere are also limita-
tions to this review. First, the literature search strategy
may be not comprehensive and thus we were unable
to incorporate all relevant interventions into this sys-
tematic review. Second, the categorization of interven-
tions into each socioecological level was based on the
primary barriers the interventions aimed to address.
erefore, the intervention levels presented in this
review may be not precise and were used to provide
examples of interventions across socioecological levels
only. ird, more than 40% of the studies are ongoing.
eir eﬀect on promoting PrEP uptake and adher-
ence is unknown. However, our primary objective is
to summarize the practical/theoretical components,
modalities, strengths, and limitations of these stud-
ies to inform the design of future PrEP interventions.
In addition, some studies with small sample size may
have low statistical power [26, 34, 35, 41, 49–51, 54].
Scaled-up RCTs as well as intervention assessment in
real-world settings are further required to replicate
their results. Finally, this systematic review identi-
ﬁes the following research opportunities based on the
gaps in existing studies: (1) expanding the spectrum of
participants (e.g., MSM with injection drug use) given
their elevated risk for HIV; (2) testing the eﬀect of dif-
ferent regimens of PrEP (e.g., daily oral pill vs. long-
acting injectable medication) on PrEP care continuum
engagement given the evidence that reduced pill bur-
den may increase PrEP uptake/adherence among MSM
[42, 50]; and (3) taking into account diﬀerent brands of
PrEP when designing and evaluating interventions in
light of the recent approval of Descovy for PrEP.
Low level of PrEP uptake and medication adherence
among MSM, especially young and/or those of color,
is concerning. Interventions to improve PrEP uptake
and adherence among MSM have been designed and
implemented at multiple socioecological levels (e.g.,
individual, interpersonal, community and healthcare/
institution) in recent years, with many of them cur-
rently in progress via a RCT. Fully evaluated interven-
tions, as well as those currently in progress, may hold
promise to help facilitate PrEP adoption among MSM;
mechanisms used to help improve one or more stages
of the PrEP continuum were also noted in the included
interventions. Areas for improvement were identiﬁed
and were presented as future research opportunities
to improve current and future PrEP interventions for
MSM in the US.
The online version contains supplementary material available at https:// doi.
org/ 10. 1186/ s12981- 022- 00456-1.
Additional le1: TableS1. Summaryof study characteristics: individ-
ual-level interventions. TableS2. Summary of study characteristics:
interpersonal-levelinterventions. TableS3. Summary ofstudy charac-
teristics: community-level interventions. TableS4. Summary of study
characteristics: healthcare system-levelinterventions. TableS5. Summary
ofstudy characteristics: multilevel interventions.
YL designed the research study. YW led the systematic review and drafted
the ﬁrst version of this manuscript. YW and YL conducted title and abstract
screening. YW conducted full text review and extracted data which was
cross-checked by YL. JM, CZ and YL reviewed and revised the manuscript.
All authors critically interpreted the results and revised the manuscript. All
authors read and approved the ﬁnal manuscript.
Availability of data and materials
All data generated or analysed during this study are included in this published
article and its Additional ﬁles.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
1 Department of Public Health Sciences, University of Rochester Medical
Center, Rochester, NY, USA. 2 Department of Health Promotion and Disease
Prevention, Stempel College of Public Health and Social Work, Florida Interna-
tional University, Miami, FL, USA. 3 School of Nursing, University of Rochester
Medical Center, Rochester, NY, USA. 4 Division of Epidemiology, Department
Page 10 of 12
Wangetal. AIDS Research and Therapy (2022) 19:28
of Public Health Sciences, University of Rochester Medical Center, 256 Crit-
tenden Blvd, Ste. 3305, Rochester, NY 14642, USA.
Received: 23 February 2022 Accepted: 16 June 2022
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