Although the United States has been a major consumer of opiates for centuries, daily consumption of opioids per capita skyrocketed in the early 21st century, with major impacts on the incidence of overdose, blood-borne infections, and life expectancy.1 Associations between substance use disorders (SUD) and outbreaks of HIV and acute viral hepatitis have received considerable attention, but less research has focused on the link between SUD and sexually transmitted infections (STIs), apart from alcohol misuse.2 An otherwise excellent 2020 report from the National Academies of Science, Engineering and Medicine on opportunities to improve services for opioid use disorder (OUD) and infectious disease did not mention any STIs.3 This narrative review describes the history of this public health crisis and direct and indirect effects opioids and specific stimulants have on high-risk sexual behaviors. We also review the epidemiology of STIs associated with opioids and stimulants in the United States and discuss opportunities for integrated interventions.
In the 1990s, the US Food and Drug Administration granted approvals for prescription opioids such as oxycodone and fentanyl to treat chronic pain,4 after assurances from their manufacturers that they were nonaddictive. This was followed by increasing reports of deaths associated with prescription opioid misuse, especially oxycodone, marketed as Oxycontin, which by 2003 was already being used by 2.8 million Americans. After an extended-release (ER) oxymorphone, OpanaER, was approved by the Food and Drug Administration in 2006, contentions about the nonaddictive properties of prescription opiates were disproven,5 but not before millions more Americans developed an OUD. In 2012, Opana's manufacturer switched to a more tamper-resistant formulation, and policy reform reduced the number of physicians who were prescribing opioids for chronic pain. This did not reduce the number of people with OUD, however, because the number of physicians prescribing medications to treat opioid disorder across the United States was limited primarily because of a number of structural barriers.3 Instead, some people with OUD began injecting Opana,6 whereas others transitioned to injecting black-tar heroin, which had become widely available and less expensive.7
In the first decade of the 21st century, the US opioid use epidemic was linked to increases in other health problems, especially in the country's most socially disadvantaged regions, like Appalachia.8 In Tennessee, Kentucky, Virginia, and West Virginia, incidence of acute hepatitis C virus (HCV) infection increased by 364% between 2006 and 2012 among people who inject drugs (PWID) younger than 30 years.9 In 2015, an HIV outbreak occurred among PWID in a rural county in southern Indiana, which quickly spread to their sexual partners, leading to a community-level HIV prevalence of 5%.10 Subsequent HIV outbreaks among PWID occurred in other rural and suburban counties, such as those in West Virginia, Massachusetts, and Washington.11,12 Nationally, the number of overdose deaths associated with prescription opioids, heroin, and fentanyl soared, with annual US overdose deaths from 2017 to 2019 surpassing that for HIV/AIDS at its peak. In 2018, an estimated 10.3 million Americans 12 years or older misused opioids in the past year (9.9 million of whom misused prescription pain relievers and 808,000 people used heroin).13 These trends were compounded by a concomitant rise in stimulant use; from 2015 to 2018, 1.6 million Americans reported using methamphetamine in the past year,14 of whom nearly half met the criteria for a methamphetamine use disorder.
DIRECT AND INDIRECT INFLUENCES OF SUBSTANCE USE ON SEXUAL BEHAVIORS
Substance use and misuse can have a direct and/or an indirect effect on sexual behaviors15,16 that can predispose to STIs. Some substances have a direct effect on sexual behaviors due to mood-altering effects on the brain.17 Alcohol is the most frequently used substance to facilitate sex, as it can relax inhibitions18 and increase motivations to engage in sex. In one study of STI clinic clients, men reported drinking more alcohol and having more sexual partners than women, but among women, alcohol use was associated with a higher number of sexual partners.19 After alcohol, marijuana is the most commonly used psychotropic drug in the United States.20 However, there are no consistent links between marijuana use and HIV/STI transmission risks,21 with a few exceptions.22 In a review of sexual health services in primary care, marijuana use was significantly associated with multiple sexual partnerships23 among women of child-bearing age but not with HIV/STI outcomes. In a study of youth living with HIV, marijuana use was associated with STIs.24
Compared with alcohol, fewer people use stimulant drugs such as cocaine/crack, methamphetamine, and ecstasy, but their impact on sexual behaviors is profound. Stimulants are associated with increased sexual behavior among both sexes,25 although motivations for their use can differ between men and women26 and heterosexuals versus sexual minorities, especially men having sex with men (MSM).27 Methamphetamine use has been associated with enhanced sexual function28,29 and libido, sexual compulsivity,30 and reduced sensation of pain.31 Compared with nonusers, MSM reporting methamphetamine use report greater numbers of anal sex partners in a short period, longer duration of sexual activity (e.g., “sex marathons”), and physically traumatic sexual activity such as “fisting” that can rupture rectal tissue predisposing to an increased risk of STI acquisition.32–36 Among men, prolonged, heavy use of methamphetamine can cause an inability to achieve and maintain an erection.37,38 When erectile dysfunction medications became available, some users also began using them with stimulants.16
Both heterosexual and MSM methamphetamine users also report frequently engaging in anal sex and trading sex for methamphetamine.30,39 Some female sex workers (FSW) report using methamphetamine to stay awake or to cope with the occupational hazards of sex work.40 For example, in studies of FSW in Mexico, engaging in substance use before or during sexual transactions was independently associated with incidence of gonorrhea, chlamydia,41 and syphilis titers consistent with active infection.42
Recent data suggest that methamphetamine use releases proinflammatory cytokines in the gut43,44 (a key site for establishing HIV, chlamydia, and rectal gonorrheal infections).45,46 Significant variation in microbiota species in the gut has been observed for MSM living with HIV who report receptive anal intercourse and recent use of methamphetamine or marijuana.47 Considering that some STIs can contribute to inflammation from HIV to enhance inflammation within the gut,48 this direction offers a new area of research that may uncover mechanistic insights into HIV and STI transmission.
In contrast with stimulants, opioids tend to dampen interest and desire for sex49 and their influence on STI risk seems indirect, as a consequence of addiction. The physically painful withdrawal symptoms that accompany OUD can motivate high-risk sexual behaviors, such as trading sex for money or drugs, with greater dependence driving more frequent sexual transactions as well as drug use.50 Sex workers experiencing OUD withdrawal may be more likely to acquiesce to their client's demands for condomless sex for more money or in exchange for drugs.51 Opiate users may also engage in polypharmacy, for example, combining stimulants with opioids to provide libido or energy needed to engage in sex.
A form of sexualized drug use mostly engaged in by MSM involves “chemsex,” which is the use of any one or combination of alcohol, stimulants (e.g., methamphetamine, cocaine, and ecstasy), γ-hydroxybutyrate, and erectile dysfunction drugs to intensify or to prolong sexual encounters. Sexualized drug use has been documented in communities of MSM for more than 25 years52 and exists on every continent.53–57 In a systematic review of 38 studies, chemsex was reported more consistently by HIV-positive than HIV-negative MSM, primarily to enhance condomless anal intercourse.55 Unique linkages between substances, sex, and other factors are found among military personnel, where drug use was strongly associated with STIs for men who only have sex with women (MSW).58 A separate study showed similar associations between substances used, numbers of partners, and STIs in both sexes.59
Sex differences have been observed in the subjective effects and pharmacotoxicological responses to various drugs.60,61 In general, men are more likely than women to use almost all types of illicit drugs and to present at emergency departments (ED) for overdose.61 However, relative to men, women are just as likely to develop SUDs and may be more disposed to craving and relapse.61
EPIDEMIOLOGY OF STIs LINKED TO SUBSTANCE USE
In the United States, STI incidence rates are the highest in more than 25 years.62 After years of decline, incidences of syphilis, gonorrhea, and chlamydia have been on the rise, with a combined total of nearly 2.5 million cases reported to the US Centers for Disease Control and Prevention (CDC) in 2018. The US incidence of chlamydia is the highest of any bacterial STI at 692.7 cases per 100,000 for women and 380.6 cases per 100,000 among men.62 Rates of both gonorrhea and syphilis are highest among men, particularly among MSM, but have also been increasing among women.63 High rates of gonorrhea are particularly concerning given the growing threat of Neisseria gonorrhoeae, the bacteria that cause gonorrhea, that are resistant to multiple antibiotics.64
Increasing rates of primary and secondary syphilis among adults have coincided with increasing cases of congenital syphilis,62 which can result in newborn death, miscarriage, or severe lifelong physical and neurological problems.65Chlamydia trachomatis and N. gonorrhoeae infections can result in lifelong consequences including pelvic inflammatory disease, infertility, and ectopic pregnancy. Sexually transmitted infections can also increase the risk of HIV acquisition and, among those who are living with HIV, can increase the risk of onward HIV transmission.66–69 Surveillance data from the CDC do not stratify rates of STIs among transgender people; however, a recent systematic review found that the prevalence of syphilis, gonorrhea, and chlamydia ranged from 1.4% to 50.4%, 2.1% to 19.1%, and 2.7% to 24.7% in transgender women, respectively, and from 0% to 4.2%, 0% to 10.5%, and 1.2% to 11.1% in transgender men, respectively.70
Use of recreational drugs may increase the risk of both blood-borne and non–blood-borne STIs. In systematic reviews, the prevalence of HSV-2 was high among people who use drugs.71 Crack cocaine use has been consistently associated with higher STI incidence.72 A recent nationally representative survey of 18- to 25-year-olds in the United States showed that the odds of contracting STIs in the preceding year were more than 3 times higher among those who reported use of illicit drugs in the last year compared with those who did not report illicit drug use.73 In 2014 to 2018, the rate of primary and secondary syphilis increased by 171.4%, the proportion of women with primary and secondary syphilis reporting injection drug use in the past 12 months increased from 6.1% to 11.4%,74 and the rate of congenital syphilis increased by 185.3%.62,75 There was also an increase in the proportion of primary and secondary syphilis cases among MSW who reported injection drug use, from 3.7% to 7.4%,74 but this trend was not observed among MSM. In addition, in 2014 to 2018, there were substantial increases, more than doubling in some cases, for the proportions of women and MSW with primary and secondary syphilis who reported methamphetamine use (6.8%–18.9% for women, 7.4%–14.8% for MSW), heroin use (3.1%–7.3% for women, 1.8%–4.3% for MSW), or sex with a PWID (8.3%–12.6% for women, 5.8%–9.8% for MSW).74
Women may experience unique challenges to STI prevention. More than a third (34.7%) of women with primary and secondary syphilis report sex while intoxicated or on drugs, and 9.5% have exchanged sex for drugs or money.76 Female sex workers may be less likely to receive and access STI prevention services77 than other at-risk populations, and drug use among FSWs may be associated with an even higher risk of STIs compared with FSW who do not use drugs.78 Epidemics of substance use and syphilis among US heterosexual men and women can be considered syndemics, which are overlapping epidemics that share common root causes, including poverty, unemployment, intimate partner violence, and homelessness.79–83
Persons seeking treatment of STIs often have SUD. In a study of Baltimore sexually transmitted disease (STD) clinics, 57% of clients had SUD (35% alcohol, 31% cannabis, 11% opioids, and 8% stimulants),84 which is higher than expected for the general US population. Additional variations in the prevalence of substance use and misuse, and SUD are observed by sexual orientation, with sexual minorities having higher prevalence compared with their heterosexual peers (through age 25 years),85–87 with less consistent findings in later-age groups. In a prospective study of attendees at STI treatment clinics,88 latent class analysis identified 4 classes of subjects: low substance use and mostly marijuana use, 2 classes of subjects with severe club drug use (powder cocaine, γ-hydroxybutyrate, ecstasy), and a class with severe street drug use (injection drug use, heroin, cocaine). The prevalences of STI were highest for the classes with severe club drug and severe street drug use compared with STI prevalences in the other 2 classes across all sexual orientations. Notable exceptions involved the mostly marijuana use class, which showed higher STI rates than the other 3 classes for MSM and women who have sex with women. This suggests that specific subgroups of substance users who have higher STI prevalence could be targeted for interventions.
RACIAL/ETHNIC AND GEOGRAPHIC DISPARITIES IN STIs ASSOCIATED WITH SUBSTANCE USE
There are significant racial/ethnic and geographic disparities in the prevalence of both STIs and substance use.89–93 National US surveillance reports consistently indicate that gonorrhea, chlamydia, and syphilis incidences are substantially higher among racial/ethnic minorities relative to Whites.62 In 2018, African Americans had the highest rates of gonorrhea (548.9 cases per 100,000) and chlamydia (1,192.5 cases per 100,000). American Indians/Alaska Natives (AI/AN) had the second highest rates of gonorrhea (329.5 cases per 100,000) and chlamydia (784.8 cases per 100,000) in the United States. Combined, these rates were approximately 4 to 8 times the rate among Whites in 2018. Moreover, primary and secondary syphilis cases have increased for all racial/ethnic groups from 2014 to 2018, more than doubling for AI/AN (7.2–15.5 cases per 100,000) and multiracial individuals (4.6–9.4 cases per 100,000). In 2018, African Americans and Hispanics accounted for more than half of all reported primary and secondary syphilis with known racial/ethnic information.62 Geographical variations have also been well documented, with Southern states having clusters of high STI prevalence.94–96
Differing rates of illicit substance use have also been observed by race/ethnicity. According to the 2019 National Survey on Drug Use and Health, 13.1% multiracial, 11.3% AI/AN, and 9.1% White individuals 12 years and older used illicit drugs in the past year, exceeding the national average of 8.6%; whereas the proportion of African Americans, Hispanics, and Asians with past-year illicit drug use was below the national average.20
Although illicit drug use can lead to unsafe sexual practices including condomless sex and multiple sexual partners, national population-based studies suggest that racial/ethnic disparities in STIs are not fully explained by differences in individual sexual and drug use patterns.89,97 Rather, social and environmental conditions including social and sexual networks, shortage of health care providers, differential access to health services, and economic inequalities contribute to persistent disparities.98 For racial/ethnic groups residing in rural/remote regions of the United States including American Indian tribal reservations and Southern states, geographic isolation, privacy, and confidential concerns also contribute to differential STI prevalence.99–101 For example, studies have shown rurality and proximity to health care services influence STI screening and treatment.102–104 In addition, one study found that STD clinic patients were more likely to seek sexual partners in close geographic proximity.105 Where people live, work, and interact can create and sustain geographic disparities in STIs.106
The national prevalence of past-month illicit drug use, including misuse of prescription psychotherapeutics, cocaine, heroin, hallucinogens, inhalants, or methamphetamine, was 3.2% among people 12 years or older.20,74 Similar to racial/ethnic disparities with STIs, there is a geographical component to drug use patterns in the United States. In 2018, although the prevalence of past-month illicit drug use was similar in Western states (3.5%) versus Southern states (3.1%),20,74 Western states reported the highest prevalence of substance use behaviors among women and MSW with syphilis in 2018. In particular, 13.7% of MSW and 17.8% of women in the West with syphilis reported injection drug use in the past 12 months, and 25.6% of MSW and 32.1% of women with syphilis in the West reported meth use in the past 12 months.74 The 2017–2018 National Survey on Drug Use and Health found several substate regions (e.g., counties or groups of counties) in Mississippi, Alabama, Florida, and South Carolina had past-month illicit drug use prevalence estimates that were higher than the national average.107 These regions also overlapped with Southern US counties reporting some of the highest prevalence of chlamydia and gonorrhea.62
More recently, there has been a spike in synthetic opioid deaths throughout the United States, primarily driven by fentanyl.108 Northeastern states had the highest rate of synthetic opioid–involved deaths, a region of the United States also experiencing an increase in illicit fentanyl,109 although evidence of parallel increases in the West are now evident.110 A rise in heterosexual syphilis transmission has been reported in these regions as well. During a 5-year period, Western states had the highest proportion of heterosexual men and women with primary and secondary syphilis who also reported in the past year having sex with PWID. During the same 5-year period, Northeastern states experienced a slow increase in heterosexual syphilis transmission among individuals with sexual partners who were PWID.63
Overall, prior research indicates geographic heterogeneity in drug-related morbidity and mortality is driven by structural factors at the population level including economic insecurity, high unemployment, low educational attainment, and poverty.111,112 Within these regions of concentrated disadvantage, social conditions further contribute to disparate STI prevalence by race/ethnicity.113,114 A recent study found that mortgage discrimination and racial/ethnic concentration were independently associated with same race/ethnicity sexual partnerships among PWID in 19 US cities, suggesting that structural interventions to eliminate racism and discrimination could have downstream influences on STI risks.115
VENUE-BASED INTERVENTIONS
Given that many persons with SUD are at increased risk of acquiring and transmitting STIs, identifying opportunities where these individuals can obtain STI screening and treatment is in the broad interest of public health. Examples of such venues include detoxification and substance abuse treatment programs, criminal justice settings, EDs, and harm reduction programs. However, because both the epidemiologies of STIs and SUDs vary significantly by geographic region and key sociodemographic factors (e.g., sex, race/ethnicity, age, sexual minority subgroup, and socioeconomic status), implementing universal screening and treatment across all these programs is unlikely to be cost-effective. This is especially true for nonresidential programs using STI testing platforms that require considerable turnaround time, as the opportunity to diagnose and treat clients may be lost. The development of an increasing number of rapid, point-of-care tests for multiple pathogens offers hope that on-site screening and treatment can be offered for STIs of greatest public health importance.
Studies examining the utility of STI screening in SUD treatment programs have generated mixed results. In a study of an inpatient drug treatment program in Birmingham, AL, in 1999, Bachmann et al.116 found that high-risk sexual behaviors were common and the prevalence rates of C. trachomatis, N. gonorrhoeae, trichomoniasis, and syphilis were 2.3%, 1.6%, 43%, and 6%, respectively. These authors concluded that screening at SUD treatment clinics was warranted. In contrast, in a large study of people attending detoxification and methadone programs in Boston, MA, in 2001, Liebschutz and colleagues117 found 0.9% prevalence of C. trachomatis infection and 0% prevalence of gonorrhea. All Chlamydia cases were identified in detox programs. These authors recommended that universal screening in this setting was not warranted but that routine screening among younger clients and in settings with high STI prevalence should be considered. Importantly, because both of these studies preceded the worsening of the opioid epidemic, their findings may no longer be generalizable. In particular, Boston recently documented a cluster of HIV cases among PWID,118 serving as a reminder that surveillance of drug use trends could serve as an indicator about when and where screening for STIs and preexposure prophylaxis (PrEP) for HIV infection should be stepped up.
Even in settings where STI prevalence is relatively low, drug treatment programs can serve as venues where use of condoms and other contraceptives is offered in the context of improving sexual and reproductive health. Furthermore, because methadone and buprenorphine are known to be cost-effective treatment modalities for reducing OUD,3 efforts to increase their initiation and adherence among people with OUD are likely to indirectly reduce the number of STIs attributable to high-risk sexual behaviors in this population. In particular, residential programs that offer childcare, on-site reproductive health services, and a trauma-informed approach to addiction treatment may encourage greater numbers of pregnant women and those with dependent children to seek sexual and reproductive health care, which could reduce the number of congenital syphilis cases. A recent study found that mirtazapine, a drug used to treat depression, significantly reduced methamphetamine use and associated high-risk sexual behaviors among MSM, which offers hope that this treatment could also indirectly reduce STI incidence.119
Studies of STI screening in US correctional settings have more consistently indicated that such settings could be sustainable for routine screening. In a recent systematic review of screening for chlamydia, gonorrhea, and syphilis in a variety of US nonclinical sites (i.e., correctional settings, bathhouses and sex venues, and self-collected at-home testing), Bernstein and colleagues120 found that criminal justice settings such as prisons and jails tended to identify a significant proportion of asymptomatic STI cases, supporting earlier research.121 However, the value and sustainability of STI screening in the other nonclinical venues examined was not clear, in part because key metrics such as proportion of new positives treated and programmatic costs were often lacking. A modeling study found that condom provision in male prisons could significantly reduce transmission of syphilis, gonorrhea, hepatitis B virus, and HIV, but had a modest impact on controlling chlamydia.122 In a recent study of opt-out STI screening in 2 US immigration detention centers,123 8.5% tested positive for at least one STI and cost to detect any STI ranged from $500 to $961. However, half of inmates declined to be tested, which underscores the need for culturally sensitive and noncoercive approaches to STI testing and treatment.
Emergency department and urgent care clinics offer another opportunity for identifying asymptomatic STIs, while simultaneously identifying persons with SUDs who may be in need of treatment. In a systematic review of literature from 1995 to 2010, positivity of gonorrhea and chlamydia was comparable with other high-risk populations and deemed sufficient for selected screening to be cost-effective, especially if point-of-care testing is available.124 However, a recent study of urgent care clinics found that, although most could treat on-site for chlamydia and gonorrhea, they continued to rely on referrals and prescriptions for treating syphilis.125 Furthermore, in a national survey of 135 pediatric ED directors, only 16% reported having a universal STI screening program, 59% said they “always” asked parents to leave the room before asking sensitive questions, and only 18% always notified patients who tested positive for an STI.126 Additional efforts are needed to help ED providers overcome structural barriers such as knowledge of CDC guidelines, laboratory testing and reporting requirements, and creating adequate and appropriate time for obtaining sexual history and offering risk reduction counseling.124,125
Apart from the correctional system, reaching substance users who are at the highest risk of having asymptomatic STIs means extending screening outside the traditional health care system. There are now more than 200 syringe service programs (SSPs) in the United States that provide PWID sterile syringes in exchange for used ones, many of which offer ancillary services. The prevalence of STI can be high among SSP users, especially among women.127,128 In a study of 1445 SSP users in California conducted in 2000, 11% of women reported having had an STI in the prior 5 years compared with 5% among men.128 A study of SSP users in New Jersey found a prevalence of 17.5% for chlamydia or gonorrhea, with women being 3 times more likely to test positive. This study also concluded that it was feasible to co-locate STI testing and treatment within mobile and stationary SSPs with treatment completion levels that rivaled that of traditional STD control programs.127 More recently, a study of female SSP users in Philadelphia who were offered PrEP for HIV infection found that 66% initiated treatment, and adherence was higher among more frequent SSP users.129 These studies underscore the need for comprehensive sexual and reproductive health care assessments among high-risk substance users, such as those attending SSPs.
Unfortunately, historical opposition against these programs in the United States has forced many to operate illegally, despite the overturning of a Congressional ban preventing the use of federal funds to support SSPs in 2015. In 2013, a nationwide survey of SSPs130 found that, although the majority offered on-site HIV testing and counseling, the proportion offering STI screening was much lower and varied by urbanicity (50% urban, 40% rural, 27% suburban). In 2020, of 173 SSPs surveyed, 43% reported diminished services such as STI testing due to the COVID-19 epidemic, and 25% had closed down.131 In countries such as Canada and Australia, and in some Western European countries, supervised injection facilities represent yet another “touch point” where PWID can potentially be reached for STI screening and on-site treatment. To date, moral opposition has also hampered the legal implementation of these programs in the United States to the detriment of prevention programs for overdose, HIV, and STIs.
CONCLUSIONS
The US epidemics of opioid and methamphetamine use have led to dramatic increases in overdose deaths, as well as rising incidence of blood-borne and STIs. The intersection between drug use and STI epidemics is not new. The US crack epidemic in the mid-1980s was followed by similar increases in primary, secondary, and congenital syphilis associated with high-risk sexual behaviors such as trading of sex for money or drugs.132 Efforts to improve STI surveillance among substance users are needed, for example, through programs such as the National HIV Behavioral Surveillance Study. National and state-level monitoring of substance use trends, such as recent increases in methamphetamine14 and fentanyl,110 may also help policymakers and program planners decide how STI screening and treatment approaches can be tailored to local needs. However, current CDC testing and treatment guidelines do not consider people who use drugs, including PWID, to be a “special” population worthy of attention, unlike key populations such as adolescents, MSM, incarcerated populations, and pregnant women. As a result, there is no funding earmarked for sentinel surveillance and outreach programs to increase STI case finding for substance users.
When the HIV epidemic began in the early 1980s, STI prevention and treatment became a lower public health priority, and state policymakers and health departments have struggled to obtain adequate resources for STI screening and contact tracing. More recently, significant funding for the prevention and treatment of HIV, TB, and malaria has been redirected toward the COVID-19 pandemic,133 which may further tighten resources for STI prevention and treatment. In addition to these competing health priorities, there are renewed concerns that Roe vs. Wade may be rescinded, making it more difficult for uninsured people to obtain STI testing and treatment, and harder for women to seek abortions. As a consequence, rates of STIs and congenital syphilis may continue to increase, especially among economically disadvantaged people, which includes substance users.
In light of these ongoing challenges, efforts are needed to determine how to best integrate health services for populations that are at risk of substance use and syndemic infections, such as HIV, STIs, and HCV and COVID-19, which has disproportionately affected underrepresented minorities.134 Zang et al.135 recently used dynamic modeling to show that, if an opt-out approach to HIV testing was linked with SARS-CoV-2 testing campaigns, it could substantially reduce HIV incidence and direct and indirect health care costs attributable to HIV in 6 US cities. Similar modeling exercises could be used to determine how to optimize STI screening, as well as PrEP, at venues frequented by high-risk substance users. Removing structural barriers to promote uptake of medications to treat OUD would reduce the public health burden of opioid addiction but could also have a significant downstream impact on STI incidence. Cooperation is needed across agencies and sectors to address structural drivers that influence high-risk sexual networks and impede access to STI testing and treatment, and to provide integrated care delivery models for STIs and related syndemics, including HIV, HCV, and substance use.
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