REVIEW

CURRENT
OPINION Identifying and managing infectious disease
syndemics in patients with HIV
Daniel J. Bromberg a,b, Kenneth H. Mayer c,d, and Frederick L. Altice b,e,f

Purpose of review
We will present recent articles focusing on HIV synergistic interactions with other sexually transmitted infections,
tuberculosis, and hepatitis, as well as recent advances in the study of social and behavioral determinants that
facilitate this clustering of infectious disease. For each synergistic interaction, we highlight evidence-based
interventions that clinicians and policymakers should consider to tackle HIV and infectious disease syndemics.
Recent findings
Significant advances in understanding the behavioral and structural determinants of HIV and other
infectious disease synergisms have been made in the past years. Intervention strategies based on these new
models have also been developed. It is now well understood that treating infectious disease syndemics will
Downloaded from http://journals.lww.com/co-hivandaids by BhDMf5ePHKbH4TTImqenVDiEotxSR1UHSri9UYeq731yPtyf3tcRlkJ8iBDz81J6 on 08/10/2020

require a multidisciplinary and multipronged approach.

Summary
HIV is synergistic with multiple other infectious diseases because the risk behaviors that lead to HIV acquisition may
be similar to the other infections. The influence of HIV on the other infection may be due to immunosuppression
associated with disease progression resulting in increased susceptibility (e.g., HIV and tuberculosis), especially
when patients are not virologically suppressed using antiretroviral therapy. In reverse, another infectious disease
may, when not treated, influence HIV disease progression. Social/structural determinants like homelessness, mass
incarceration, and structural discrimination precipitate psychiatric comorbidity, substance use, and risky sex
behavior which lead to the spread and co-occurrence of infectious disease.
Keywords
HIV, homelessness, infectious diseases, prisons, syndemics, tuberculosis, viral hepatitis

INTRODUCTION HIV. For example, male circumcision reduces HIV

Specific infectious diseases are central to HIV-related
syndemics, particularly: tuberculosis (TB), sexually
transmitted infections (STI), hepatitis [hepatitis C/B
virus HCV/HBV], as well as other infectious diseases
in local contexts (e.g., schistosomiasis in endemic
areas). They combine with the biological and psy-
chobehavioral interactions that cluster within these
comorbid conditions and are abetted by structural
and social factors. Consequently, interrelated syn-
ergies may reinforce the expression of each condi-
tion. In this article, we discuss the biological, social/
structural and behavioral synergism related to HIV
and other infectious diseases, and how they affect
the expression of HIV disease outcomes.
Biological synergism
Biological differences play a major role in facilitat-
ing HIV transmission, and differences between indi-
viduals may make them more or less susceptible to
transmission by at least 60% because the foreskin
contains a much larger concentration of cells that
can acquire HIV than the rest of the penis [1]. In
women, proinflammatory cytokines and chemo-
kines in genital secretions due to multiple factors,
a
Department of Social and Behavioral Sciences, Yale University School
of Public Health, bYale Center for Interdisciplinary Research on AIDS,
Yale University, New Haven, Connecticut, cThe Fenway Institute, Fenway
Health, dDepartment of Medicine, Beth Israel Deaconess Medical Cen-
ter, Harvard Medical School, Boston, Massachusetts, eSection of Infec-
tious Diseases, Department of Medicine, Yale University School of
Medicine and fDepartment of Epidemiology of Microbial Diseases, Yale
University School of Public Health, New Haven, Connecticut, USA
Correspondence to Frederick L. Altice, MD, Section of Infectious Dis-
eases, Department of Medicine, Yale University School of Medicine, 135
College Street, Suite 323, New Haven, CT 06510-2283, USA.
Tel: +1 203 737 2883; fax: +1 203 737 4051;
e-mail: frederick.altice@yale.edu, paula.dellamura@yale.edu
Curr Opin HIV AIDS 2020, 15:232–242
DOI:10.1097/COH.0000000000000631

www.co-hivandaids.com Volume 15  Number 4  July 2020

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

 Identifying and managing infectious disease syndemics Bromberg et al.

may be geographically colocated, for example, TB

KEY POINTS
 HIV interacts with other infectious diseases often in
bidirection, synergistic ways.
 Clustering of behavioral precursors to infectious disease
explain why we observe high rates of infectious co-
occurrence in certain populations.
 Structural factors like minority stress, homelessness, and
incarceration heavily exacerbate behavioral precursors
to infectious disease.
and HIV. In many cases, the influence of HIV on the
other infection may be due to immunosuppression
associated with disease progression resulting in
increased susceptibility (e.g., HIV and TB), especially
when patients are not virologically suppressed using
antiretroviral therapy (ART). In reverse, another
infectious disease may, when not treated, influence
HIV disease progression [e.g., increased risk of neu-
rosyphilis on people with HIV (PWH)]. Table 1
shows synergistic relationships between HIV and
other infectious diseases.

ranging from the use of some douching products to
STIs, can increase risk for acquiring HIV [2].
HIV is synergistic with multiple other infectious
diseases because the risk behaviors that lead to HIV
acquisition may be similar to the other infections,
for example, sex for STI and injection drug use and
viral hepatitis (HCV/HBV), or synergistic infections
Sexually transmitted infections
From 2012 to 2016, the global incidence of curable
STIs (chlamydia, gonorrhea, nongonococcal ure-
thritis, trichomoniasis, and syphilis) increased from
357 to 376 million incident cases among people
aged 15–49 years [20]. In the presence of STIs, the
inflammatory response by the host can also increase

Table 1. Description of biological synergisms with HIV infections and potential interventions

Comorbid Impact of comorbid Impact of one or both comorbid

infectious disease infectious disease HIV infectious diseases Potential interventions

Tuberculosis None Increased likelihood of reactivation of latent Integrated care services for HIV
TB infection and TB
Decreasing CD4 in HIV patients linked to Treatment of latent TB infection
increased risk of TB acquisition in HIV test and treat strategies that
noninfected persons focus on same-day ART
Decreasing CD4 in HIV patients is treatment strategies [3]
associated with more atypical disease
presentation, including extrapulmonary TB
HIV does not impact TB treatment
Syphilis Syphilis increases risk of Decreasing CD4 in HIV patients linked to Routine screening for syphilis in
HIV acquisition [4] accelerated progression to neurosyphilis PWH
Syphilis may increase the and atypical presentations [10,11] Integration of STI and HIV services
progression of HIV High rates of syphilis acquisition in a subset
disease [5,6], although of MSM with viral suppression with
data are inconclusive increased levels of condomless sex
[7–9]
Other STIs Ulcerative and HIV increases infection risk [13,14] for men Integrated services for HIV and
inflammatory STIs and women [15], and accelerates STI STI
increase risk of HIV disease progression [16] Syndromic STI treatment
acquisition [12] STI increases HIV infectiousness in treatment
STI can increase HIV naı̈ve or nonadherent patients
replication through
cytokine activation and
upregulate genital tract
HIV RNA
HCV None HIV changes rate of fibrosis from HCV [17] Integrated HIV/HCV services
HCV treatment with direct-acting
antiviral replication treatment as
prevention microelimination
strategies [18 ,19]
&

Harm reduction services in PWID

to prevent reinfection

ART, antiretroviral therapy; HCV, hepatitis C virus; PWH, people with HIV; PWID, people who inject drugs; STIs, sexually transmitted infections; TB, tuberculosis.

1746-630X Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved. www.co-hivandaids.com 233

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

HIV syndemics

Table 2. Social and structural synergisms

Social/Structural Impact on other

factor Impact on ID synergistic factors Potential interventions

Incarceration Increases crowding leading to risk of TB Increases injection drug In-prison MOUD with postrelease
transmission use continuity [26 ,27 ]
&& &

Increases HIV, STI, HBV, and HCV risk Increases depression In-prison NSP [28]
behavior Decriminalizing drug use to reduce
incarceration levels
Homelessness and Crowding in shelters increases risk of TB Increases psychiatric Nonabstinence-contingent housing
housing transmission comorbidities and Housing vouchers
substance use disorders Reducing incarceration [29]
Minority stigma and Leads to increased HIV, STI, HBV, and Increases psychiatric Psychotherapy tailored to sexual minority
intraminority stress HCV risk behavior comorbidities and populations, such as the ESTEEM
substance use disorders model [30 ]
&&

Changing stigmatizing laws and policies

relating to gay and bisexual men [31]

HBV, hepatitis B virus; HCV, hepatitis C virus; ID, injection drug; MOUD, medications for opioid use disorder; NSP, needle and syringe programs; STI, sexually
transmitted infection; TB, tuberculosis.

production of inflammatory cytokines and recruit
immune cells to the genital tract [21–25], which in
turn increases the risk for HIV acquisition and trans-
mission. Ulcerative STIs like herpes simplex virus
(HSV) and syphilis not only create a proinflamma-
tory response that facilitates HIV transmission, but
they also erode the epithelial barrier to trans-
mission.
HIV coinfection affects syphilis and HSV presen-
tation and expression as the HIV-associated immu-
nosuppression increases in direct proportion to
lower CD4 lymphocyte counts. Synergy between
HIV and syphilis has long been understood [37].
Not only is syphilis incidence in PWH is several-fold
greater than in the general population, but the
presentation of syphilis may be more severe or atyp-
ical, particularly in more immunosuppressed PWH
who are more likely to develop multiple, deeper, or
larger chancres [38,39]. Moreover, syphilis pro-
gresses to tertiary syphilis 3.5 times more quickly
in PWH than those without HIV [39], especially in
more immunosuppressed PWH [40]. Despite early

Table 3. Behavioral synergisms

Impact on other syner-

Behavioral factor Impact on ID gistic factors Potential interventions

Substance use Injection drug use is a
pathway of HIV and
HCV transmission
Increases STI and HBV risk
behavior
Interferes with medication
adherence
Psychiatric comorbidity Increases HIV, HCV, HBV,
and STI risk behavior
Interferes with ART and
other medication
adherence
Violence Increases HIV, HCV, HBV,
and STI risk behavior
Increases psychiatric
comorbidity
Associated with increased
experiences of violence
Increases substance use
Increases psychiatric
comorbidity and
substance use
Intimate partner violence
increases risk of
homelessness
Community needle and syringe programs
MOUD
SBIRT
Contingency management
Relapse prevention
Cognitive behavior therapy
Depression screening among gay and bisexual
men
Tailored cognitive behavioral therapy like
ESTEEM for gay/bisexual men
CBT-based interventions that tailored to victims
of violence [32,33]
Web-based and remote interventions for victims
of IPV [34]
Economic strengthening interventions for victims
combined with and gender transformative
interventions for perpetrators [35]
Housing interventions for victims of IPV [36]

ART, antiretroviral therapy; CBT, cognitive behavioral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus; ID, injection drug; IPV, intimate partner violence;
MOUD, medications for opioid use disorder; SBIRT, screening, brief intervention, and referral to treatment; STI, sexually transmitted infection.

234 www.co-hivandaids.com Volume 15  Number 4  July 2020

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

 Identifying and managing infectious disease syndemics Bromberg et al.
research to the contrary [5,6], recent data does not
show that syphilis increases HIV progression [7,8].
HIV and genital HSV have a bidirectional effect
on each other. Reactivation of genital HSV increases
HIV viral replication, risk of HIV transmission, and
disease progression. Coinfection with HSV in PWH
results in increased HSV viral shedding, risk of HSV
transmission, and frequency and severity of HSV
symptoms [41]. Patients who are coinfected with
HIV and genital HSV may benefit from treatment
with antiviral medications for HSV, including
chronic viral suppression [42].
Inflammatory bacterial STIs that cause urethritis
(e.g., gonorrhea, chlamydia, ureaplasma, etc.) have
been associated with increased risk for HIV [43,44],
especially among amphetamine users [45].
In many settings, testing is limited and expen-
sive, so syndromic treatment is common. Syn-
dromic treatment misses a substantial number of
people with STIs, and managing STIs can be opti-
mized through the use of low-cost point-of-care
&&
testing [46 ]. In addition, integrating HIV and STI
services can address this biological synergism. Ser-
vice integration for women with HIV has been
shown to increase Pap smear screening, even when
sexual health screening and education did not [47].
Integrating such services for MSM with HIV appear
to be feasible and acceptable [48]. Integrating these
services has also been shown to increase provision of
preexposure prophylaxis for MSM without HIV [49].
Integrated HIV and STI service delivery models make
empiric sense, but need more evaluation in clinical
trials and implementation studies. For MSM
experiencing high levels of stigma, and in which
such sexual health services are not available, home
testing for HIV and STIs could emerge as an effective
strategy to address this synergism [50].
Tuberculosis
HIV increases risk of TB infection and disease pro-
gression and TB slows CD4 recovery and increases
HIV progression and death among PWH. Treatment
of both HIV with ART and latent TB infection (LTBI)
with preventive therapy mitigate the impact of
coinfection. More advanced HIV results in increased
rate of reactivation of LTBI with increased likelihood
of atypical and extrapulmonary TB, which may be
challenging to diagnose. Moreover, TB increases
HIV replication [51], resulting in increased HIV
progression and death, while HIV accelerates TB
disease progression, and impacts TB diagnosis and
management [52]. Of the 10 million people diag-
nosed with TB in 2018, 860 000 (8.6%) were among
PWH. Mortality among those coinfected with HIV/
TB was high (29.2%) and accounted for 33% of the
1746-630X Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
770 000 deaths among PWH [53], including the
majority (69%) of HIV/TB patients on ART in South
Africa [54].
Integrated HIV/TB programs, especially in high
prevalence settings, are both feasible and improve
health outcomes for both conditions. Key elements
for such services include universal testing and treat-
ment of HIV irrespective of CD4, screening and
treatment for both TB and LTBI among all PWH,
and patient-centered support and monitoring to
ensure adherence and treatment retention [55].
Among people who inject drugs (PWID), integrating
services for addiction, HIV and TB demonstrate
improved addiction treatment, HIV and TB out-
comes in a study of PWH in Ukraine [56]. Despite
the benefits observed in this strategy, most low and
middle income countries fail to deploy this strategy.
Hepatitis C virus
HCV is the most prevalent chronic viral infection
and prevalence is highest among PWID. Among
PWID, HCV prevalence ranges from 52 to 90%
and is 9 to 40% among PWH, depending on region.
Although HCV does not appear to alter HIV progres-
sion, the immunosuppressive nature of HIV, espe-
cially in those with decreasing CD4 counts, results
in accelerated liver fibrosis and increased morbidity
and death in HIV/HCV coinfected patients. Though
the mechanism of HIV and its related influence on
accelerated fibrosis is not known [57], early treat-
ment of HCV in HIV/HCV patients is associated with
halting or improving fibrosis progression [58]. Initi-
ating ART in HIV/HCV and restoring CD4 counts
can reduce the rate of fibrosis in HIV/HCV patients.
Although universal test and treat strategies have
generally been successful in generalized epidemics,
ART coverage levels in PWID with HIV remain low,
related to patient-level factors like avoiding health-
&
care due to stigma or fear of discrimination [59 ], or
HIV healthcare providers withholding ART from
PWID until they are abstinent from drugs [60,61].
Microelimination strategies of HCV in HIV/HCV
coinfected patients [62], potentially using an inte-
grated HIV/HCV service delivery model [63], can
reduce the negative consequences of HIV/HCV coin-
fection. One such model initiated HCV treatment in
over two-thirds of patients, but cured only about
half of the HCV infections in PWH [64]. The rela-
tively low microelimination outcome in this setting
was likely due to the lack of integration with addic-
tion treatment services including opioid agonist
therapies (OAT) and challenges in engaging PWID
who mistrust the healthcare system. Harm reduc-
tion services should be incorporated within these
settings not only to reduce transmission to injecting
www.co-hivandaids.com 235
HIV syndemics
partners, but also to reduce the risk of reinfection.
Mathematical models suggest that a combination of
OAT and syringe services programs (SSP) is opti-
mally integrated in any HCV treatment as preven-
&
tion efforts [18 ,19].
Social and structural synergism
We define social and structural synergism as the
relationship between social determinants of health
and the ways in which they modify disease risk,
clinical presentation, or epidemiology. Social and
structural factors interact with behavioral determi-
nants of health in complex and multifaceted ways,
explained in a simplified taxonomy below (Table 2).
Incarceration
Over 10.3 million people are incarcerated with 2.2
million in the United States [65], with both sexual
and injection-related transmission of infectious dis-
ease occurring [66]. Within prison drug injection is
variable, but in Kyrgyzstan [67], Indonesia [68], and
Ukraine [69], where HIV transmission is increasing,
within prison injection is high. This behavior also
increases transmission of viral hepatitis (HCV/HBV),
and after release from prison, injection-related drug
risk is several-fold higher due to disruption of injec-
tion networks and social instability [70]. Crowing
additionally contributes to elevated TB risk, espe-
cially for PWH who are at higher risk for TB out-
breaks [71,72].
Interventions that are likely to reduce the nega-
tive consequences of incarceration on HIV, viral
hepatitis (HCV/HBV), and TB include decriminal-
ization of drug use [73], and for those remaining,
scale-up of medications for opioid use disorder
(MOUD) in prisons. Because the postrelease period
&&
is risky [26 ] for those with or without HIV, it is
crucial to markedly reduce the negative consequen-
ces of incarceration both through decriminalization
of drug use, but also by releasing people in prison
with substance use disorders and nonviolent
offenses. Two recent systematic reviews also support
to use of MOUD initiated within prison and conti-
nuity postrelease as being effective [74,75]. Another
strategy to reduce blood-borne virus transmission
within prison include SSP [28,76]. Naloxone for
overdose prevention for prisoners transitioning to
the community is highly acceptable [77] and effec-
tive programs are now underway [78].
Homelessness and housing
Homelessness is associated with a 46-fold increased
risk of TB, and a four-fold increased risk of HCV [79].
STI infections among homeless youth are markedly
236 www.co-hivandaids.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
higher than among the general population [80].
Transitions through housing are especially problem-
atic for people leaving jails [81] and for anyone
evicted from stable housing, there are increased chla-
mydia and gonorrhea infections [82]. Access to med-
ical care, linkage to ART, and medication adherence
has been shown to be a persistent problem for people
unstably housed [83], and when housing is priori-
tized for PWH, their HIV treatment outcomes
improve [84]. In addition, homelessness interacts
with many other social and biological synergisms
of HIV.
Many formerly incarcerated individuals become
homeless postrelease, leading to an interactive
‘revolving door’ effect [85]. Homeless populations
have a 10-fold increased risk of TB acquisition when
compared with the general population [86]. TB out-
breaks in the United States also frequently originate
in homeless shelters [87].
Persons experiencing homelessness have high
levels of substance use disorders, mental illness, and
HIV risk [88]. Among youth, many are part of the
lesbian, gay, bisexual, transgender, and queer
(LGBTQþ) community and when homeless, they
experience elevated levels of drug use and injection
initiation [89], reinforced by high rates of depressive
disorders [90]. The syndemic effects of housing
instability and policy, incarceration, STIs, and HIV
is currently being investigated by the Justice, Hous-
ing, and Health Study [91], which will publish their
research on the topic in the coming years.
Like for other social factors, addressing housing
instability will require an integrated approach. Rent
supplements coupled with mental health support
are an effective way to improve housing stability for
homeless adults with mental illnesses [92]. Case
management has been consistently associated with
improved mental health and substance use disorder
outcomes when compared with treatment as usual.
When case management is coupled with ‘assertive
community treatment’ (essentially an improved and
well staffed case management team), rates of home-
lessness and mental health outcomes are further
improved [93]. Housing first [94] and respite care
[95] interventions are also effective.
Stigma, minority stress, and intraminority
stress
Gay and bisexual men experience high rates of depres-
&
sion [96 ], anxiety, substance use disorders, and other
psychiatric comorbidities [97] that put them at
increased risk of HIV, STI, and HCV acquisition.
Minority stress theory posits that gay and bisex-
ual men’s frequent interactions with heterosexism
are a source of chronic stress, and lead to adverse
Volume 15  Number 4  July 2020
 Identifying and managing infectious disease syndemics Bromberg et al.
mental health outcomes [98]. Minority stress has
been shown to be associated with HIV and STI risk
behavior, adverse mental health outcomes, and sub-
stance use [99]. Although most research examining
the association between minority stress and infec-
tious disease has been conducted in western coun-
tries, recent scholarship has started to observe similar
associations worldwide [100], implying that homo-
phobia and infectious disease are strongly linked
regardless of cultural context. Sexual minority stress
is linked to a host of biological outcomes, including
overall physical health, immune response, and out-
comes specific to HIV, cardiovascular, hormonal, and
&&
metabolic health, and cancer [101 ].
&&
To address minority stress, Burton et al. [30 ] have
introduced the ESTEEM intervention, which is a tai-
lored cognitive behavioral therapy model specifically
designed to reduce and mitigate the effects of minority
stress. Online interventions are effective in low-
resource settings [102]. Oldenburg et al. [31] have
found that stigmatizing state-level policies were
strongly associated with minority stress among gay
and bisexual state residents, implying that passing
LGBTQþ-favorable legislation may be an effective
way to impact the syndemic problem of minority
stress, infectious disease, and psychiatric comorbidity.
&&
A recent article by Pachankis et al. [103 ] intro-
duces a new theory of intraminority stress among gay
and bisexual men. The theory proposes that a portion
of the excessive burden of mental health disorders
among sexual minority men can be explained by
status-based pressures from within their communi-
ties to maintain markers of social status, namely:
masculine norms, attractiveness, and wealth. Empir-
ically testing this theory, the team found that intra-
minority stress theory was a better explanatory model
for mental health outcomes than minority stress
theory. Another recent article by Burton et al.
&&
[104 ] found that the same intraminority stressors
were associated with lower aversion to HIV and STI
risk behavior, like condomless sex. Intraminority
stress is also likely associated with increased sub-
stance and therefore HCV transmission, although
this has yet to be investigated. As of yet, no tailored
intervention for intraminority stress exists.
Transgender women also have a heightened bur-
den of HIV infections. Although data are scarce and are
not representative, meta-analysis estimates a 19.1%
pooled HIV prevalence for transgender women world-
wide [105]. Evidence also suggests that transgender
women have elevated rates of HCV infections, with a
recent cross-sectional study in San Francisco showing
an anti-HCV seroprevalence nine times higher among
transgender women than the general population
[106], suggesting that harm reduction measures
should be tailored to transgender populations.
1746-630X Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Much of the theory linking minority stress to
HIV/STI risk behavior is applicable to transgender
individuals [107,108]; however, transgender people
also face distinct challenges that put them at
increased risk of infectious disease. Transgender peo-
ple face high rates of identity-based violence world-
wide [109,110] and are incarcerated at higher rates
than the general population. In the United States,
transgender women are incarcerated at twice the rate
of the general population, and Black transgender
women have a 10-fold increased risk of incarceration
[111]. Homelessness and incarceration may lead to
heightened rates of TB among transgender people
[112], though robust prevalence data are lacking.
As African Americans made up 13% of the US
population in 2018, but 42% of all HIV diagnoses
[113], the role of race and structural racism in regards
to infectious disease cannot be overstated. Black MSM
do not have higher rates of risky sex behavior than
their white counterparts [114], and evidence support-
ing explanatory models of Black MSM elevated HIV
incidence is inconclusive [115]. Explanatory models
for the high HIV incidence include lower access to
healthcare services, increased rates of incarceration
and stigma [115], and selective sexual partnering
leading to higher likelihood of intercourse with an
HIV-positive partner [116–119]. The role of structural
racism in understanding the HIV and infectious dis-
ease syndemics among African Americans in the
United States and ethnic minorities around the world
is a topic that deserves further study to ascertain
causal mechanisms.
Intersectional stressors impact the mental
health of individuals holding multiple marginalized
identities [120] (e.g., Black MSM). Tailored interven-
tions for such intersectional stressors are currently
in development [121].
Behavioral synergism
We define behavioral synergism as the relationship
between nonbiological, individual-level determi-
nants of health, the pathways between them and
infectious disease transmission, and their impact on
the clinical expression and treatment of infectious
disease. We include both psychological synergisms
(e.g., psychiatric comorbidities) and synergisms
relating to interactions with the environment and
others (e.g., substance use) in this category (Table 3).
Substance use and psychiatric comorbidities
The prevalence and morbidity of depression among
gay and bisexual men in the United States and
&
elsewhere has reached epidemic proportions [96 ],
both exceeding that of HIV/AIDS. Depression is
known to influence HIV and STI sexual risk behavior
www.co-hivandaids.com 237
HIV syndemics

among sexual minority men [122–125], as well as Injection drug use

interfere with medication adherence [126]. The
prevalence of other stress-sensitive psychiatric con-
ditions like anxiety is also very high among gay and
bisexual men [97]. These psychiatric comorbidities
are associated with increased drug use [127] and
sexual risk behavior [128].
Sexualized drug use (Chemsex)
Sexualized drug use, especially of stimulants, has
evolved as a major driver of HIV transmission, espe-
cially among MSM. Although general prevalence
&
data is lacking, meta-analysis [129 ] of studies
recruiting MSM from sexual health clinics and dat-
ing and sex apps had chemsex prevalences of 0–14%
[130,131]. Stimulants are associated with elevated
risk for depressive symptoms and suicide ideation
along with elevated rates of condomless sex, result-
ing in increased HIV and STI transmission [132–
134]. Those involved in chemsex are less likely to
seek medical care when they need it [135], often
resulting in suicide, suggesting that low sexual
health clinics must be more facile with dealing with
stimulant use, which is challenging to treat. For
individuals with stimulant disorders, an effective
intervention is wide-scale preexposure prophylaxis
&&
(PrEP) [136 ].
There are an estimated 15.6 million PWID world-
wide. Of the 15.6 million PWID worldwide, 17.8%
are PLHIV, 9.1% are HBV-positive, and 52.3% are
HCV-positive [137]. One in three PWID meet the
Diagnostic and Statistical Manual of Mental Disor-
ders, 5th Edition’s definition for depressive disorder
diagnoses, and one in four PWID has attempted
&&
suicide [138 ].
The gold standard for the treatment of opioid
use disorder (OUD) is MOUD [139]. Models of
MOUD delivery that combine HIV and HCV treat-
ment, PrEP for HIV, and behavioral health services
for HIV are needed to target the syndemic of OUD,
HIV, and HCV [140]. Although some research on
these integrated services exist, the relative effective-
ness of different levels of integration is unknown.
CONCLUSION: OVERLAPPING
BIOLOGICAL, BEHAVIORAL AND SOCIAL,
AND STRUCTURAL SYNERGIES
In this review, we synthesize synergistic compo-
nents of syndemic systems into biological, social/
structural, and behavioral categories. Though this
makes for convenient categorization, all elements’
syndemics are thoroughly intertwined and often

FIGURE 1. Diagram of infectious disease syndemic pathways for people who inject drugs. This figure illustrates the ways in
which different levels of synergies impact infectious disease syndemics for people who inject drugs. Arrows within the model
indicate the direction of the synergistic effects. Larger arrows represent interactions that have been qualitatively deemed more
significant for their respective populations.

238 www.co-hivandaids.com Volume 15  Number 4  July 2020

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

 Identifying and managing infectious disease syndemics Bromberg et al.

FIGURE 2. Diagram of infectious disease syndemic pathways for MSM. This figure illustrates the ways in which different levels
of synergies impact infectious disease syndemics for MSM. Arrows within the model indicate the direction of the synergistic
effects. Larger arrows represent interactions that have been qualitatively deemed more significant for their respective
populations.

mutually reinforce one another. In Figs. 1 and 2, we
represent the ways in which different levels of syn-
ergies impact infectious disease syndemics for PWID
and MSM, respectively.
Important features contribute differently to spe-
cific populations; for example, depression reduces
adherence to ART. Although PWID and MSM experi-
ence epidemic rates of depressive disorders that often
exceed 50%, this is a cross-cutting synergy for most
key populations. Incarceration and drug use are simi-
larly bidirectional. PWID, relative to MSM, experi-
ence much more profound levels of incarceration
(lifetime 50–90%), which in turn results in higher-
risk drug injection within prison and increased HIV
and HCV transmission. Crowding increases the risk
of TB exposure, which can result in increased HIV
transmission and expression of HIV-related disease.
Notably, there is substantial sociodemographic vari-
ation within both the PWID and MSM populations;
some elements of the syndemic models in Figs. 1 and
2 will be more appropriate to some subsegments of
these populations than others.
Acknowledgements
The authors would like to thank Amanda R Liberman for
proofreading this article.
Financial support and sponsorship
The authors would like to acknowledge training grants
from the National Institutes of Health (T32MH20031)
and research funding (P30AI060354, R01 DA033679,
K24 DA017072).
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Prodger JL, Kaul R. The biology of how circumcision reduces HIV suscept-
ibility: broader implications for the prevention field. AIDS Res Ther 2017;
14:49.
2. Liebenberg LJ, Masson L, Arnold KB, et al. Genital–systemic chemokine
gradients and the risk of HIV acquisition in women. J Acquir Immune Defic
Syndr 2017; 74:318–325.
3. Labhardt ND, Ringera I, Lejone TI, et al. Effect of offering same-day ART vs
usual health facility referral during home-based HIV testing on linkage to care
and viral suppression among adults with HIV in Lesotho: the CASCADE
randomized clinical trial. JAMA 2018; 319:1103–1112.
4. Solomon MM, Mayer KH, Glidden DV, et al. Syphilis predicts HIV incidence
among men and transgender women who have sex with men in a preexposure
prophylaxis trial. Clin Infect Dis 2014; 59:1020–1026.
5. Buchacz K, Patel P, Taylor M, et al. Syphilis increases HIV viral load and
decreases CD4 cell counts in HIV-infected patients with new syphilis
infections. AIDS 2004; 18:2075–2079.

1746-630X Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved. www.co-hivandaids.com 239

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

HIV syndemics
6. Kofoed K, Gerstoft J, Mathiesen LR, Benfield T. Syphilis and human im-
munodeficiency virus (HIV)-1 coinfection: influence on CD4 T-cell count,
HIV-1 viral load, and treatment response. Sex Transm Dis 2006;
33:143–148.
7. Huang L, Cheng W, Han Z, et al. Syphilis infection does not affect im-
munodeficiency progression in HIV-infected men who have sex with men in
China. Int J STD AIDS 2020; 31:488–496.
8. Weintrob A, Gu W, Qin J, et al. Syphilis co-infection does not affect HIV
disease progression. Int J STD AIDS 2010; 21:57–59.
9. Rompalo AM, Joesoef MR, O’Donnell JA, et al. Clinical manifestations of early
syphilis by HIV status and gender: results of the syphilis and HIV study. Sex
Transm Dis 2001; 28:158–165.
10. Rompalo AM, Lawlor J, Seaman P, et al. HOOK III EW. Modification of
syphilitic genital ulcer manifestations by coexistent HIV infection. Sex Transm
Dis 2001; 28:448–454.
11. Zellan J, Augenbraun M. Syphilis in the HIV-infected patient: an update on
epidemiology, diagnosis, and management. Curr HIV/AIDS Rep 2004;
1:142–147.
12. Ding J, Rapista A, Teleshova N, et al. Neisseria gonorrhoeae enhances HIV-1
infection of primary resting CD4þ T cells through TLR2 activation. J Immunol
2010; 184:2814–2824.
13. Cameron DW, D’Costa L, Maitha G, et al. Female to male transmission of
human immunodeficiency virus type 1: risk factors for seroconversion in men.
Lancet 1989; 334:403–407.
14. Wang CC, McClelland RS, Reilly M, et al. The effect of treatment of vaginal
infections on shedding of human immunodeficiency virus type 1. J Infect Dis
2001; 183:1017–1022.
15. Cu-Uvin S, Hogan JW, Caliendo AM, et al. Association between bacterial
vaginosis and expression of human immunodeficiency virus type 1 RNA in the
female genital tract. Clin Infect Dis 2001; 33:894–896.
16. Van de Perre P, Segondy M, Foulongne V, et al. Herpes simplex virus and
HIV-1: deciphering viral synergy. Lancet Infect Dis 2008; 8:490–497.
17. Greub G, Ledergerber B, Battegay M, et al. Clinical progression, survival, and
immune recovery during antiretroviral therapy in patients with HIV-1 and
hepatitis C virus coinfection: the swiss HIV cohort study. Lancet 2000;
356:1800–1805.
18. Zelenev A, Li J, Shea P, et al. Modeling combination HCV treatment and
& prevention strategies in a network of people who inject drugs in the USA. Clin
Infect Dis 2020. [Epub ahead of print]
The modeling study shows that hepatitis C virus (HCV) treatment with direct acting
antivirals as prevention is the most effective strategy for the micro-elimination of
HCV, and that concurrent OAT scale-up may have a synergistic effect in micro-
elimination efforts. This is the first modeling article to address HCV treatment as
prevention as a micro-elimination strategy.
19. Zelenev A, Li J, Mazhnaya A, et al. Hepatitis C virus treatment as prevention in
an extended network of people who inject drugs in the USA: a modelling
study. Lancet Infect Dis 2018; 18:215–224.
20. Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea,
trichomoniasis and syphilis: global prevalence and incidence estimates. Bull
World Health Organ 2019; 97:548P–562P.
21. Masson L, Mlisana K, Little F, et al. Defining genital tract cytokine signatures
of sexually transmitted infections and bacterial vaginosis in women at high
risk of HIV infection: a cross-sectional study. Sex Transm Infect 2014;
90:580–587.
22. Levine WC, Pope V, Bhoomkar A, et al. Increase in endocervical CD4
lymphocytes among women with nonulcerative sexually transmitted dis-
eases. J Infect Dis 1998; 177:167–174.
23. Fichorova RN, Desai PJ, Gibson FC 3rd, Genco CA. Distinct proinflamma-
tory host responses to Neisseria gonorrhoeae infection in immortalized
human cervical and vaginal epithelial cells. Infect Immun 2001;
69:5840–5848.
24. Reddy B, Rastogi S, Das B, et al. Cytokine expression pattern in the genital
tract of Chlamydia trachomatis positive infertile women–implication for T-cell
responses. Clin Exp Immunol 2004; 137:552–558.
25. Rebbapragada A, Wachihi C, Pettengell C, et al. Negative mucosal synergy
between Herpes simplex type 2 and HIV in the female genital tract. AIDS
2007; 21:589–598.
26. Sugarman OK, Bachhuber MA, Wennerstrom A, et al. Interventions for
&& incarcerated adults with opioid use disorder in the United States: a sys-
tematic review with a focus on social determinants of health. PLoS One
2020; 15:e0227968.
The article reviews interventions for incarcerated opioid use disorder (OUD) in the
United States and finds that medications for opioid use disorder (MOUD) ad-
ministered throughout criminal justice involvement is associated with improved
postrelease OUD treatment outcomes. This review offers a number of insights
important to the implementation of OUD in prisons, including: early initiation of
prison MOUD is associated with favorable treatment outcomes and that social
determinants of health are often competing priorities for incarcerated PWID and
should be addressed during MOUD implementation.
27. Puglisi LB, Bedell PS, Steiner A, Wang EA. Medications for opioid use
& disorder among incarcerated individuals: a review of the literature and focus
on patient preference. Curr Addic Rep 2019; 6:365–373.
This is the first systematic review to assess how incorporation of patient prefer-
ences into MOUD service delivery in prisons impacts treatment utilization.
240 www.co-hivandaids.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
28. Lazarus JV, Safreed-Harmon K, Hetherington KL, et al. Health outcomes for
clients of needle and syringe programs in prisons. Epidemiol Rev 2018;
40:96–104.
29. Munthe-Kaas HM, Berg RC, Blaasvær N. Effectiveness of interventions to
reduce homelessness: a systematic review and meta-analysis. Campbell
Syst Rev 2018; 14:1–281.
30. Burton CL, Wang K, Pachankis JE. Psychotherapy for the spectrum of sexual
&& minority stress: application and technique of the ESTEEM treatment model.
Cogn Behav Pract 2019; 26:285–299.
The article outlines the techniques and theoretical basis of the ESTEEM treatment
model, a therapeutical model designed to alleviate minority stress among gay and
bisexual men.
31. Oldenburg CE, Perez-Brumer AG, Hatzenbuehler ML, et al. State-level
structural sexual stigma and HIV prevention in a national online sample of
HIV-uninfected men who have sex with men in the United States. AIDS 2015;
29:837–845.
32. Arroyo K, Lundahl B, Butters R, et al. Short-term interventions for survivors of
intimate partner violence: a systematic review and meta-analysis. Trauma
Violence Abuse 2017; 18:155–171.
33. Darawshy NA-S, Gewirtz A, Marsalis S. Psychological intervention and
prevention programs for child and adolescent exposure to community
violence: a systematic review. Clin Child Fam Psychol Rev 2020. [Epub
ahead of print]
34. Anderson EJ, McClelland J, Krause CM, et al. Web-based and mHealth
interventions for intimate partner violence prevention: a systematic review
protocol. BMJ Open 2019; 9:e029880.
35. Gibbs A, Jacobson J, Kerr Wilson A. A global comprehensive review of
economic interventions to prevent intimate partner violence and HIV risk
behaviours. Global Health Action 2017; 10(Suppl. 2):1290427.
36. Klein L, Chesworth BR, Howland-Myers JR, et al. Housing interventions for
intimate partner violence survivors: a systematic review. Trauma Violence
Abuse 2019. [Epub ahead of print]
37. Hobbs E, Vera JH, Marks M, et al. Neurosyphilis in patients with HIV. Prac
Neurol 2018; 18:211–218.
38. Zetola NM, Klausner JD. Syphilis and HIV infection: an update. Clin Infect Dis
2007; 44:1222–1228.
39. Taylor MM, Aynalem G, Olea LM, et al. A consequence of the syphilis
epidemic among men who have sex with men (MSM): neurosyphilis in
Los Angeles, 2001–2004. Sex Transm Dis 2008; 35:430–434.
40. Ghanem KG, Moore RD, Rompalo AM, et al. Neurosyphilis in a clinical cohort
of HIV-1-infected patients. AIDS 2008; 22:1145–1151.
41. Thurman A, Doncel G. Herpes simplex virus and HIV: genital infection
synergy and novel approaches to dual prevention. Int J STD AIDS 2012;
23:613–619.
42. Ransome Y, Thurber KA, Swen M, et al. Social capital and HIV/AIDS in the
United States: knowledge, gaps, and future directions. SSM Popul Health
2018; 5:73–85.
43. Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted
diseases, and genital tract inflammation facilitating local pathogen transmis-
sion and acquisition. Am J Reprod Immunol 2011; 65:308–316.
44. Kularatne RS, Niit R, Rowley J, et al. Adult gonorrhea, chlamydia and syphilis
prevalence, incidence, treatment and syndromic case reporting in South
Africa: estimates using the Spectrum-STI model, 1990–2017. PLoS One
2018; 13:e0205863.
45. Katz DA, Dombrowski JC, Bell TR, et al. HIV incidence among men who have
sex with men following diagnosis with sexually transmitted infections. Sex
Transm Dis 2016; 43:249.
46. Wi TE, Ndowa FJ, Ferreyra C, et al. Diagnosing sexually transmitted infec-
&& tions in resource-constrained settings: challenges and ways forward. J Int
AIDS Soc 2019; 22:e25343.
This is the most recent systematic review of sexually transmitted infections (STI)
testing and service provision in resource constrained settings. The authors
conclude that point-of-care testing are urgently needed in low-resource settings
and will increase STI screening among vulnerable populations and those highest at
risk.
47. Kennedy CE, Haberlen SA, Narasimhan M. Integration of sexually transmitted
infection (STI) services into HIV care and treatment services for women living
with HIV: a systematic review. BMJ Open 2017; 7:e015310.
48. Moss T, Martin CW, Klausner JD, Brown BJ. Integration of screening for
syphilis, hepatitis C, and other sexually transmitted infections with HIV testing
in a community-based HIV prevention program in Miami, Florida. LGBT
Health 2014; 1:82–85.
49. Liu AY, Cohen SE, Vittinghoff E, et al. Preexposure prophylaxis for HIV
infection integrated with municipal- and community-based sexual health
services. JAMA Intern Med 2016; 176:75–84.
50. Bilardi JE, Walker S, Read T, et al. Gay and bisexual men’s views on rapid
self-testing for HIV. AIDS Behav 2013; 17:2093–2099.
51. Toossi Z, Johnson JL, Kanost RA, et al. Increased replication of HIV-1 at sites
of Mycobacterium tuberculosis infection: potential mechanisms of viral
activation. J Acquir Immune Defic Syndr 2001; 28:1–8.
52. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin
Microbiol Rev 2011; 24:351–376.
53. Organization WH. Global tuberculosis report. Geneva (Switzerland): World
Health Organization; 2019.
Volume 15  Number 4  July 2020
 Identifying and managing infectious disease syndemics Bromberg et al.
54. Wong EB, Omar T, Setlhako GJ, et al. Causes of death on antiretroviral
therapy: a post-mortem study from South Africa. PLoS One 2012; 7:e47542.
55. Harries A, Schwoebel V, Monedero-Recuero I, et al. Challenges and oppor-
tunities to prevent tuberculosis in people living with HIV in low-income
countries. Int J Tuberc Lung Dis 2019; 23:241–251.
56. Bachireddy C, Soule MC, Izenberg JM, et al. Integration of health services
improves multiple healthcare outcomes among HIV-infected people who
inject drugs in Ukraine. Drug Alcohol Depend 2014; 134:106–114.
57. Chrysanthidis T, Loli G, Metallidis S, Germanidis G. Mechanisms of accel-
erated liver fibrosis in HIV–HCV coinfection. AIDS Rev 2017; 19:148–155.
58. Bruno G, Saracino A. Direct-acting antivirals for HIV/HCV co-infected
individuals: as good as it gets? Curr HIV Res 2017; 15:422–433.
59. Go VF, Hershow RB, Kiriazova T, et al. Client and provider perspectives on
& antiretroviral treatment uptake and adherence among people who inject
drugs in Indonesia, Ukraine and Vietnam: HPTN 074. AIDS Behav 2019;
23:1084–1093.
The international qualitative study shows that there are large gaps between
provider and people who inject drugs (PWID) patient perception of barriers to
antiretroviral therapy and HIV testing. PWID patients tend to focus on stigma and
systemic barriers to testing and treatment, while providers focus individual barriers.
60. Ferro EG, Culbert GJ, Wickersham JA, et al. Physician decisions to defer
antiretroviral therapy in key populations: implications for reducing human
immunodeficiency virus incidence and mortality in Malaysia. Open Forum
Infect Dis 2017; 4:ofw219.
61. Westergaard RP, Ambrose BK, Mehta SH, Kirk GD. Provider and clinic-level
correlates of deferring antiretroviral therapy for people who inject drugs: a
survey of North American HIV providers. J Int AIDS Soc 2012; 15:10.
62. The Lancet Hiv. Microelimination could be a big deal for HCV and HIV
services. Lancet HIV 2018; 5:e605.
63. Lions C, Laroche H, Zaegel-Faucher O, et al. Hepatitis C virus-microelimina-
tion program and patient trajectories after hepatitis C virus cure in an
outpatient HIV clinical unit. Eur J Gastroenterol Hepatol 2019. [Epub ahead
of print]
64. Rizk C, Miceli J, Shiferaw B, et al. Implementing a comprehensive HCV clinic
within an HIV clinic: a model of care for HCV micro-elimination. Open Forum
Infect Dis 2019. [Epub ahead of print]
65. Walmsley R. World prison population list. In: Institute for criminal policy
research. 11th ed. London: Birkbeck, University of London; 2015:; Retrieved
from http://www prisonstudies org/sites/default/files/resources/downloads/
world_prison_population_list_11th_edition_0 pdf.
66. Moazen B, Saeedi Moghaddam S, Silbernagl MA, et al. Prevalence of drug
injection, sexual activity, tattooing, and piercing among prison inmates.
Epidemiol Rev 2018; 40:58–69.
67. Azbel L, Wegman MP, Polonsky M, et al. Drug injection within prison in
Kyrgyzstan: elevated HIV risk and implications for scaling up opioid agonist
treatments. Int J Prison Health 2018; 14:175–187.
68. Culbert GJ, Waluyo A, Iriyanti M, et al. Within-prison drug injection among
HIV-infected male prisoners in Indonesia: a highly constrained choice. Drug
Alcohol Depend 2015; 149:71–79.
69. Izenberg JM, Bachireddy C, Wickersham JA, et al. Within-prison drug
injection among HIV-infected Ukrainian prisoners: prevalence and correlates
of an extremely high-risk behaviour. Int J Drug Policy 2014; 25:845–852.
70. Altice FL, Azbel L, Stone J, et al. The perfect storm: incarceration and the
high-risk environment perpetuating transmission of HIV, hepatitis C virus, and
tuberculosis in Eastern Europe and Central Asia. Lancet 2016;
388:1228–1248.
71. Stuckler D, Basu S, McKee M, King L. Mass incarceration can explain
population increases in TB and multidrug-resistant TB in European and
central Asian countries. Proc Natl Acad Sci U S A 2008; 105:
13280–13285.
72. Dolan K, Wirtz AL, Moazen B, et al. Global burden of HIV, viral hepatitis, and
tuberculosis in prisoners and detainees. Lancet 2016; 388:1089–1102.
73. Csete J, Kamarulzaman A, Kazatchkine M, et al. Public Health and Interna-
tional Drug Policy. Lancet 2016; 387:1427–1480.
74. Moore KE, Roberts W, Reid HH, et al. Effectiveness of medication assisted
treatment for opioid use in prison and jail settings: A meta-analysis and
systematic review. Journal of Substance Abuse Treatment 2019;
99:32–43.
75. Sugarman OK, Bachhuber MA, Wennerstrom A, et al. Interventions for
incarcerated adults with opioid use disorder in the United States: A sys-
tematic review with a focus on social determinants of health. PloS one 2020;
15:e0227968.
76. J€urgens R, Ball A, Verster A. Interventions to reduce HIV transmission related
to injecting drug use in prison. Lancet Infect Dis 2009; 9:57–66.
77. Parmar MK, Strang J, Choo L, et al. Randomized controlled pilot trial of
naloxone-on-release to prevent post-prison opioid overdose deaths. Addic-
tion 2017; 112:502–515.
78. Zucker H, Annucci AJ, Stancliff S, Catania H. Overdose prevention for
prisoners in New York: a novel program and collaboration. Harm Reduct J
2015; 12:51.
79. Beijer U, Wolf A, Fazel S. Prevalence of tuberculosis, hepatitis C virus, and
HIV in homeless people: a systematic review and meta-analysis. Lancet Infect
Dis 2012; 12:859–870.
1746-630X Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
80. Caccamo A, Kachur R, Williams SP. Narrative review: sexually transmitted
diseases and homeless youth–what do we know about sexually transmitted
disease prevalence and risk? Sex Transm Dis 2017; 44:466–476.
81. Zelenev A, Marcus R, Kopelev A, et al. Patterns of homelessness and
implications for HIV health after release from jail. AIDS Behav 2013;
17:181–194.
82. Niccolai LM, Blankenship KM, Keene DE. Eviction from renter-occupied
households and rates of sexually transmitted infections: a county-level
ecological analysis. Sex Transm Dis 2019; 46:63–68.
83. Aidala AA, Wilson MG, Shubert V, et al. Housing status, medical care, and
health outcomes among people living with HIV/AIDS: a systematic review.
Am J Public Health 2016; 106:e1–e23.
84. Rajabiun S, Tryon J, Feaster M, et al. The influence of housing status on the
HIV continuum of care: results from a multisite study of patient navigation
models to build a medical home for people living with HIV experiencing
homelessness. Am J Public Health 2018; 108(S7):S539–S545.
85. Kushel MB, Hahn JA, Evans JL, et al. Revolving doors: imprisonment among
the homeless and marginally housed population. Am J Public Health 2005;
95:1747–1752.
86. Bamrah S, Yelk Woodruff RS, Powell K, et al. Tuberculosis among the
homeless, United States, 1994–2010. Int J Tuberc Lung Dis 2013;
17:1414–1419.
87. Gupta V, Sugg N, Butners M, et al. Tuberculosis among the homeless –
preventing another outbreak through community action. N Eng J Med 2015;
372:1483–1485.
88. Linton SL, Celentano DD, Kirk GD, Mehta SH. The longitudinal association
between homelessness, injection drug use, and injection-related risk beha-
vior among persons with a history of injection drug use in Baltimore, MD.
Drug Alcohol Depend 2013; 132:457–465.
89. Feng C, DeBeck K, Kerr T, et al. Homelessness independently predicts
injection drug use initiation among street-involved youth in a Canadian
setting. J Adolesc Health 2013; 52:499–501.
90. Hadland SE, Marshall BD, Kerr T, et al. Depressive symptoms and patterns of
drug use among street youth. J Adolesc Health 2011; 48:585–590.
91. Keene DE, Niccolai L, Rosenberg A, et al. Rental assistance and adult self-
rated health. J Health Care Poor Underserved 2020; 31:325–339.
92. Stergiopoulos V, Mejia-Lancheros C, Nisenbaum R, et al. Long-term effects
of rent supplements and mental health support services on housing and
health outcomes of homeless adults with mental illness: extension study of
the at home/chez soi randomised controlled trial. Lancet Psychiatry 2019;
6:915–925.
93. Luchenski S, Maguire N, Aldridge RW, et al. What works in inclusion health:
overview of effective interventions for marginalised and excluded popula-
tions. Lancet 2018; 391:266–280.
94. Woodhall-Melnik JR, Dunn JR. A systematic review of outcomes associated
with participation in housing first programs. Housing Stud 2016;
31:287–304.
95. Doran KM, Ragins KT, Gross CP, Zerger S. Medical respite programs for
homeless patients: a systematic review. J Health Care Poor Underserved
2013; 24:499–524.
96. Bromberg, Daniel and Paltiel, A. David and Busch, Susan H, and Pachankis,
& John E., Has depression surpassed HIV as a burden to gay and bisexual
men’s health in the United States? (19 August 2019). Available at SSRN:
https://ssrn.com/abstract=3439575 or http://dx.doi.org/10.2139/ssrn.
3439575.
This is a preprint of an article that shows that the morbidity in years lived with
disability of major depressive disorder among American gay and bisexual men
exceeded that of HIV in the same population. The article highlights that epidemic
rates of psychiatric disorders among gay and bisexual men are a critical compo-
nent of HIV and other STI syndemics.
97. King M, Semlyen J, Tai SS, et al. A systematic review of mental disorder,
suicide, and deliberate self harm in lesbian, gay and bisexual people. BMC
Psychiatry 2008; 8:70.
98. Meyer IH. Minority stress and mental health in gay men. J Health Soc Behav
1995; 36:38–56.
99. Hatzenbuehler ML, Nolen-Hoeksema S, Erickson SJ. Minority stress pre-
dictors of HIV risk behavior, substance use, and depressive symptoms:
results from a prospective study of bereaved gay men. Health Psychol
2008; 27:455–462.
100. Sun S, Budge S, Shen W, et al. Minority stress and health: a grounded
theory exploration among men who have sex with men in China and
implications for health research and interventions. Soc Sci Med 2020;
252:112917.
101. Flentje A, Heck NC, Brennan JM, Meyer IH. The relationship between minority
&& stress and biological outcomes: a systematic review. J Behav Med 2019.
[Epub ahead of print]
This is the first systematic review to assess the relationship between sexual
minority (nonheterosexual) stress and all biological health outcomes, including
infectious disease.
102. Pachankis JE, Williams SL, Behari K, et al. Brief online interventions for
LGBTQ young adult mental and behavioral health: a randomized controlled
trial in a high-stigma, low-resource context. J Consult Clin Psychol 2020;
88:429–444.
www.co-hivandaids.com 241
HIV syndemics
103. Pachankis JE, Clark KA, Burton CL, et al. Sex, status, competition, and
&& exclusion: intraminority stress from within the gay community and gay and
bisexual men’s mental health. J Pers Soc Psychol 2020. [Epub ahead of print]
The article is the first to introduce and provide empirical support for the theory of
intraminority stress which posits that some of gay and bisexual men’s stress-
sensitive mental health conditions (like depression and anxiety) can be explained
by stressful pressures within the gay/bi community to maintain markers of status
like masculinity, attractiveness, and wealth.
104. Burton CL, Clark KA, Pachankis JE. Risk from within: intraminority gay
&& community stress and sexual risk-taking among sexual minority men. Ann
Behav Med 2020. [Epub ahead of print]
The article is the first to link intraminority stress theory to sexual risk behavior
among gay and bisexual men, providing a link between intraminority stress and HIV
and STIs.
105. Baral SD, Poteat T, Strömdahl S, et al. Worldwide burden of HIV in
transgender women: a systematic review and meta-analysis. Lancet Infect
Diseases 2013; 13:214–222.
106. Wilson EC, Turner C, Lin J, et al. Hepatitis C seroprevalence and engage-
ment in related care and treatment among trans women. J Viral Hepat 2019;
26:923–925.
107. Hendricks ML, Testa RJ. A conceptual framework for clinical work with
transgender and gender nonconforming clients: an adaptation of the minority
stress model. Prof Psychol Res Pract 2012; 43:460.
108. Rich AJ, Williams J, Malik M, et al. Biopsychosocial mechanisms linking
gender minority stress to HIV comorbidities among black and latina trans-
gender women (LITE plus): protocol for a mixed methods longitudinal study.
JMIR Res Protoc 2020; 9:e17076.
109. Wirtz AL, Poteat TC, Malik M, Glass N. Gender-based violence against
transgender people in the United States: a call for research and program-
ming. Trauma Violence Abuse 2020; 21:227–241.
110. King R, Nanteza J, Sebyala Z, et al. HIV and transgender women in Kampala,
Uganda–Double Jeopardy. Cult Health Sex 2019; 21:727–740.
111. Poteat TC, Malik M, Beyrer C. Epidemiology of HIV, sexually transmitted
infections, viral hepatitis, and tuberculosis among incarcerated transgender
people: a case of limited data. Epidemiol Rev 2018; 40:27–39.
112. Centers for Disease Control and Prevention (CDC). HIV-related tuberculosis
in a transgender network-Baltimore, Maryland, and New York City area,
1998–2000. MMWR Morb Mortal Wkly Rep 2000; 49:317–320.
113. Hess KL, Johnson SD, Hu X, et al. Diagnoses of HIV infection in the United
States and dependent areas. 20172018.
114. Millett GA, Peterson JL, Wolitski RJ, Stall R. Greater risk for HIV infection of
black men who have sex with men: a critical literature review. Am J Public
Health 2006; 96:1007–1019.
115. Maulsby C, Millett G, Lindsey K, et al. HIV among black men who have sex
with men (MSM) in the United States: a review of the literature. AIDS Behav
2014; 18:10–25.
116. Millett GA, Peterson JL, Flores SA, et al. Comparisons of disparities and risks
of HIV infection in black and other men who have sex with men in Canada, UK,
and USA: a meta-analysis. Lancet 2012; 380:341–348.
117. Tieu H-V, Murrill C, Xu G, Koblin BA. Sexual partnering and HIV risk among
black men who have sex with men: New York City. J Urban Health 2010;
87:113–121.
118. Koblin BA, Mayer KH, Eshleman SH, et al. Correlates of HIV acquisition in a
cohort of Black men who have sex with men in the United States: HIV
prevention trials network (HPTN) 061. PLoS One 2013; 8:e70413.
119. Schneider JA, Cornwell B, Ostrow D, et al. Network mixing and network
influences most linked to HIV infection and risk behavior in the HIV epidemic
among black men who have sex with men. Am J Public Health 2013;
103:e28–e36.
120. Jackson SD, Mohr JJ, Sarno EL, et al. Intersectional experiences, stigma-
related stress, and psychological health among Black LGBQ individuals. J
Consult Clin Psychol 2020; 88:416–428.
121. Flentje A. AWARENESS: development of a cognitive–behavioral interven-
tion to address intersectional minority stress for sexual minority men living
with HIV who use substances. Psychotherapy (Chic) 2019; 57:35–49.
242 www.co-hivandaids.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
122. Safren SA, Reisner SL, Herrick A, et al. Mental health and HIV risk in men who
have sex with men. J Acquir Immune Defic Syndr 2010; 55(Suppl
2):S74–S77.
123. Reisner SL, Mimiaga MJ, Skeer M, et al. Clinically significant depressive
symptoms as a risk factor for HIV infection among black MSM in Massachu-
setts. AIDS Behav 2009; 13:798–810.
124. Reisner SL, Mimiaga MJ, Safren SA, Mayer KH. Stressful or traumatic life
events, posttraumatic stress disorder (PTSD) symptoms, and HIV sexual risk
taking among men who have sex with men. AIDS Care 2009; 21:
1481–1489.
125. Hatzenbuehler ML, O’cleirigh C, Mayer KH, et al. Prospective associations
between HIV-related stigma, transmission risk behaviors, and adverse mental
health outcomes in men who have sex with men. Ann Behav Med 2011;
42:227–234.
126. Gonzalez JS, Batchelder AW, Psaros C, Safren SA. Depression and HIV/
AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune
Defic Syndr 2011; 58:181–187.
127. Conner KR, Pinquart M, Duberstein PR. Meta-analysis of depression and
substance use and impairment among intravenous drug users (IDUs).
Addiction 2008; 103:524–534.
128. Crepaz N, Marks G. Are negative affective states associated with HIV sexual
risk behaviors? A meta-analytic review. Health Psychol 2001; 20:291–299.
129. Maxwell S, Shahmanesh M, Gafos M. Chemsex behaviours among men who
& have sex with men: a systematic review of the literature. Int J Drug Policy
2019; 63:74–89.
Although other systematic reviews have examined sexualized drug use behavior,
this is the first systematic review to examine exclusively chemsex activity among
MSM.
130. Rosińska M, Gios L, Nöstlinger C, et al. Prevalence of drug use during sex
amongst MSM in Europe: results from a multisite bio-behavioural survey. Int J
Drug Policy 2018; 55:231–241.
131. Hammoud MA, Vaccher S, Jin F, et al. The new MTV generation: using
methamphetamine, TruvadaTM, and ViagraTM to enhance sex and stay safe.
Int J Drug Policy 2018; 55:197–204.
132. Lim SH, Akbar M, Wickersham JA, et al. The management of methamphe-
tamine use in sexual settings among men who have sex with men in Malaysia.
Int J Drug Policy 2018; 55:256–262.
133. Reback CJ, Fletcher JB, Swendeman D. Associations between sociodemo-
graphic characteristics and sexual risk behaviors among methamphetamine-
using men who have sex with men. Substance Use Misuse 2018;
53:1826–1833.
134. Pufall E, Kall M, Shahmanesh M, et al. Sexualized drug use (‘chemsex’) and
high-risk sexual behaviours in HIV-positive men who have sex with men. HIV
Med 2018; 19:261–270.
135. Bourne A, Reid D, Hickson F, et al. ‘Chemsex’ and harm reduction need
among gay men in South London. Int J Drug Policy 2015; 26:1171–1176.
136. Farrell M, Martin NK, Stockings E, et al. Responding to global stimulant use:
&& challenges and opportunities. Lancet 2019; 394:1652–1667.
This is the most recent global systematic review on global stimulant use.
137. Degenhardt L, Peacock A, Colledge S, et al. Global prevalence of injecting
drug use and sociodemographic characteristics and prevalence of HIV, HBV,
and HCV in people who inject drugs: a multistage systematic review. Lancet
Glob Health 2017; 5:e1192–e1207.
138. Colledge S, Larney S, Peacock A, et al. Depression, posttraumatic stress
&& disorder, suicidality and self-harm among people who inject drugs: a sys-
tematic review and meta-analysis. Drug Alcohol Depend 2020; 207:107793.
This is the first systematic review to synthesize the evidence related to psychiatric
comorbidities among people who inject drugs. The article found that an estimated
42% of PWID experience severe depressive symptomology and 28.7% have a
depression diagnosis.
139. Connery HS. Medication-assisted treatment of opioid use disorder: review of
the evidence and future directions. Harv Rev Psychiatry 2015; 23:63–75.
140. Rich KM, Bia J, Altice FL, Feinberg J. Integrated models of care for individuals
with opioid use disorder: how do we prevent HIV and HCV? Curr HIV/AIDS
Rep 2018; 15:266–275.
Volume 15  Number 4  July 2020