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Official websites use. Share sensitive information only on official, secure websites. Address correspondence to Dr. Although rates of methamphetamine use continue to increase throughout the United States, little is known about the individuals who sell methamphetamine at the street level. This exploratory study examined the prevalence and correlates of drug-dealing behavior in a sample of heterosexually-identified methamphetamine users who were participants in a sexual risk reduction intervention in San Diego, CA. These characteristics, particularly intensity of drug use and hostility, may be associated with greater resistance to drug treatment and lower success in treatment programs. Drug dealers and drug users are often viewed as distinct groups in the context of social, legal, and public health risk, but many drug users also participate in the drug economy, blurring this distinction. Drug users' involvement in the drug economy may include a number of activities, including trading or selling drugs to support their own habits, 1 or packaging and transporting drugs. A complex set of characteristics may explain the behaviors of the drug user who is part of the drug economy, rendering a differentiation of the users and dealers difficult. In Baltimore, MD, drug users involved in the drug economy were using drugs significantly more often and were significantly more likely to be injectors than those who were not involved in the drug economy. These drug users, who were predominantly heroin users, also had larger drug and social networks than other drug users. Throughout the US, drug dealers have been a primary target of law enforcement crackdowns on drug markets. As evidenced in studies of injection drug users, police crackdowns have been associated with reluctance to access needle exchange and overdose prevention programs. In order to develop effective intervention programs, it is imperative that we enhance our understanding of the social, behavioral, and psychological correlates of drug-dealing behavior. Social stigma and threat of legal punishment are documented barriers to research participation among adult drug dealers. Studies of adolescents suggest that the sale of drugs, particularly cannabis, occurs primarily within informal friendship networks. Among adult drug users, the two most common reasons that street-level dealers sell drugs are to generate personal income and to cover the cost of their own drug use. In Kerr et al. Behavioral factors associated with drug dealing included frequent heroin and cocaine injection, binge drug use, syringe lending, recent overdose, and receiving help injecting. Studies that have examined psychological characteristics as potential correlates of drug-dealing behavior are few in number. We reasoned that specific characteristics of the drug-dealing environment, including the experience of violence, social stigma, lack of trust in relationships, and isolation from mainstream society 4 , 5 , 15 may be associated with elevated levels of psychological symptoms among drug dealers. In a recent study, drugs users who reported involvement in criminal activity, primarily drug dealing, had significantly more symptoms of psychological distress ie, anxiety, depressive symptoms as compared to those who did not report criminal activity. The present study sought to identify socio-demographic, behavioral, and psychological correlates of drug-dealing behavior among methamphetamine users. We focused on methamphetamine users for several reasons. First, methamphetamine dealing may be a highly prevalent activity among users due to the stimulating quality of methamphetamine and the associated desire for repetitive use that creates a high demand. Second, methamphetamine use is associated with risky sexual behavior and high rates of HIV infection and other sexually transmitted infections. Baseline data from a sample of heterosexually-identified, methamphetamine-using men and women were used in these analyses. One-on-one counseling sessions used motivational interviewing, 22 social cognitive strategies, 23 and cognitive behavioral therapy 24 to promote behavior change. Eligible participants were at least 18 years of age, self-identified as heterosexual, and reported having had unprotected vaginal or anal sex with an opposite-sex partner in the previous two months. Study eligibility also required that participants used methamphetamine at least twice during the past two months, and at least once during the past 30 days. Participants were recruited through multiple sources, including community-based service providers, poster and media campaigns, street outreach, and referrals from enrolled participants. A dichotomized variable was created for age using a median split where less than or equal to 38 years was coded 1 younger and greater than 38 years was coded 0 older. The interviewer-administered survey collected data on socio-demographics, lifetime and recent substance use history, modes of administration of methamphetamine and other drug use, and binge use, as previously described. Amount of methamphetamine used in the past 30 days was recorded as number of grams. Dealing was assessed by asking respondents if they had sold or traded methamphetamine in the past two months. Sexual sensation-seeking was assessed using the item scale developed by Kalichman et al. Each item was rated on a 5-point scale ranging from 0 not at all to 5 extremely. Summary scores ranged in value from 0 to Assertiveness was measured using 5 items from the drug item subscale of The Assertion Questionnaire in Drug Use. The assertion scale has good test-retest reliability and adequate convergent and discriminant validity. Group differences in continuous and categorical variables were examined using t -test and chi-square, respectively. Logistic regression analyses were used to identify factors associated with methamphetamine dealing in the last 2 months. A total of four logistic regressions were performed. In the first logistic equation, seven socio-demographic variables were examined in relation to methamphetamine dealing ie, gender, age, ethnicity, education, income, employment status, living arrangement. The second equation examined five substance use variables in relation to methamphetamine dealing ie, binge use of methamphetamine, frequency of use, number of grams of methamphetamine used, injection use, and frequency of alcohol use. A third logistic equation examined psychological characteristics of the individual in relation to dealing behavior ie, depressive symptoms, anxiety, hostility, assertiveness in turning down drugs, sexual sensation-seeking. The final logistic regression included all variables that were significantly associated with methamphetamine-dealing behavior in the first three logistic equations. The average age was Fifty-nine percent reported having a felony conviction. Participants who reported dealing methamphetamine in the past two months were significantly more likely to be male, younger, and have a felony conviction compared to their counterparts who did not deal methamphetamine see Table 1. Fifty-two percent of the sample self-identified as binge users of methamphetamine. Twenty-six percent reported injecting methamphetamine in the past two months. Mean number of grams of methamphetamine used in the past 30 days was Fourteen percent of the sample did not consume alcohol in the past month. Participants who reported dealing methamphetamine were significantly more likely to report injecting methamphetamine, used methamphetamine on more days in the previous month, and used more grams of methamphetamine in the past 30 days compared to those who did not deal drugs see Table 1. Participants who reported dealing methamphetamine scored significantly higher on BSI hostility and sexual sensation-seeking see Table 1. In the first logistic regression, socio-demographic variables were examined in relation to methamphetamine-dealing behavior. Ethnicity, employment status, income, education, and living arrangements were not associated with methamphetamine-dealing behavior. In the second logistic regression, five substance use variables were examined in relation to methamphetamine-dealing behavior. Binge use of methamphetamine and frequency of alcohol use were not associated with dealing behavior. In a third logistic regression, psychological characteristics of the individual were examined in relation to methamphetamine-dealing behavior. BSI hostility symptoms and sexual sensation-seeking were associated with drug-dealing behavior. Depressive symptoms, assertiveness in turning down drugs, and anxiety symptoms were not associated with dealing methamphetamine. The final logistic regression included the seven variables that were associated with methamphetamine-dealing behavior in the above analyses. Five variables were significantly associated with methamphetamine dealing Table 2. Being male, younger age, greater frequency of methamphetamine use, injection use of methamphetamine, and higher BSI hostility scores were factors independently associated with dealing methamphetamine in the past two months. Because of the high rate of felony convictions among methamphetamine dealers identified in the univariate analyses, we conducted a separate logistic regression with the felony variable added to the final logistic equation reported in Table 2. In this large sample of methamphetamine users who were participants in a sexual and drug risk reduction intervention in San Diego, CA, nearly one third reported dealing methamphetamine within the last two months. Our finding that methamphetamine dealers tended to be younger, higher intensity users is consistent with previous studies in other drug-using populations. For example, Kerr et al. Individuals who are arrested but not charged with trafficking or selling violations should be referred to drug treatment programs. Kubiak, Arfken, Swartz and Koch 32 proposed that brief interventions during the arrest phase may motivate individuals to seek more comprehensive substance use treatment. Schwartz and colleagues 33 found that interim methadone maintenance provided to community-based drug users in Baltimore, MD who were on the waiting list for treatment was effective in reducing drug use. However, the lack of a proven substitution therapy for methamphetamine limits the kinds of drug treatment modalities that may be offered. The relationship between drug dealing and psychological characteristics of the individual eg, hostility, sexual sensation seeking suggests that dealers who come into contact with the criminal justice system should also have access to psychological services. In the United Kingdom and the US, drug treatment programs that address the mental health of arrestees have been shown to reduce drug use and drug-related criminal activity. Several other studies have reported that drug treatment for offenders has beneficial effects for the individual, and enhances public health and safety. Incarceration of drug-abusing dealers in the absence of effective treatment programs is likely to result in a return to drug-related criminal behavior. Indeed, it appears that having a felony conviction was not an effective deterrent for the majority of drug dealers in our sample. Seventy-seven percent of those who dealt methamphetamine in the past two months reported a felony convinction in their past. This study also highlights the importance of hostility as a correlate of drug-dealing behavior among methamphetamine users. Hostility is distinguishable from anger, which is conceptualized as an emotional state or personality trait. It is possible that hostile individuals are less threatened or intimidated by the dangers and challenges of drug dealing. Indeed, hostility in the family environment has been implicated in the incidence of substance use, delinquency, and dysfunctional coping among adolescents. A study of violent male substance users reported significantly higher levels of hostility and suspiciousness compared to non-violent substance users. Longitudinal, prospective research is needed to understand the reciprocal relationship between hostility and drug-dealing behavior as well as the trajectory of hostility symptoms over time among methamphetamine dealers. Behavioral or overt expressions of hostility are also strongly associated with antisocial personality disorder. In terms in treatment, methamphetamine dealers who exhibit high levels of hostility may benefit from from antidepressant treatment eg, fluoxetine 44 and cognitive behavioral therapy eg, cognitive restructuring, relaxation. We found that men had approximately twice the odds of being a drug dealer compared to women. Several explanations are plausible. Men may have more opportunity to deal drugs. Indeed, previous research has shown that males have greater opportunity to purchase drugs compared to females. A qualitative study of drug users in Tijuana, Mexico found that male drug users tended to acquire and use drugs in more public settings with a large number of people, whereas female drug users tended to buy and use drugs from the same person and places, and had fewer drug users in their social networks. It is also likely that women, particularly those who have children, are less likely to engage in drug dealing activities because of the value placed on family roles as well as the care and protection of young children. In a qualitative study of methamphetamine users in three sites, Morgan and Joe 21 found that gender differences in drug-related activity ie, dealing, distribution, manufacturing varied by study site. In San Francisco, the proportion of women who sold methamphetamine was greater than for men; the opposite was true in Honolulu. More research is needed to ascertain the role of women as dealers in the illicit drug economy. It is possible that women dealers are a hidden population that are in urgent need of intervention. Future studies should also seek to identify and understand gender differences in motivations and barriers associated with drug-dealing behavior so that effective gender-responsive treatment programs can be developed. Being younger was associated with a greater odds of drug-dealing behavior. Age may be a marker for a range of factors, including economic need, social inexperience, and age-related personality traits such as fearlessness, thrill-seeking, and impulsivity. Also, younger persons may be more likely than their older counterparts to view the social and economic benefits of drug dealing as outweighing the threat of legal punishment. More research is needed to understand the mechanisms that link age to drug-dealing behavior. This information could be critical to the development of drug treatment programs targeting drug dealers. Taken together, these findings indicate that socio-demographic factors, substance use variables, and psychological symptoms are important factors to consider in the development of an empirically-based profile of methamphetamine dealers. Additional factors should be examined in future studies. Data on the social networks of dealers could be key to understanding drug-dealing behavior and developing effective treatment programs. Fitzgerald 5 reported that the social networks of low-level drug dealers are comprised almost exclusively of drug-using friends and family, as well as others who are involved in the drug market eg, paying customers, producers, enforcers. In addition, drug dealers are often isolated from those in the dominant social community. Thus, programs that integrate substance use treatment with the development of a supportive non-drug-using social network may increase the likelihood of exiting from a drug-dealing lifestyle. The present study contributes to our understanding of drug-dealing behavior by focusing on an understudied group of individuals who deal methamphetamine. However, like all studies, this study is not without limitations. The volunteer nature of this project limits the generalizability of our research findings. The inclusion of treatment-seeking participants in our sample may further limit the generalizability of our findings to the broader population of methamphetamine dealers. This study was also limited to heterosexual methamphetamine users, despite continuing popularity of this drug among gay and bisexual men in the US. To our knowledge, the present sample did not include any high-level distributors that functioned within well-organized selling organizations that manufacture or transport methamphetamine across international borders. Thus, the factors associated with drug-dealing behavior are likely to differ depending on their role in the local drug economy. Also, we did not provide participants with a formal definition of drug dealing, and we do not know to what extent participants shared a common definition. Future studies should include descriptive data that details the frequency and amount of drugs sold, the number and characteristics of buyers, the location of drug deals, strategies for acquiring clients, and the variety of drugs sold. Another limitation stems from the self-report nature of the data. In particular, this study may underestimate the prevalence of methamphetamine-dealing behavior. Given that drug dealers are a primary target of law enforcement efforts, it is not unreasonable to assume that individuals would not be forthcoming about this activity, despite confidentiality assurances. However, we have no reason to suspect that under-reporting would have biased the associations we observed in an upward direction. It is also of note that the drug dealer question was asked in a two-month time frame so that we could identify a sufficient number of methamphetamine dealers for these analyses. It is possible that the disparate timeframes associated with our measure of drug dealing and drug use behaviors eg, amount and frequency of methamphetamine use were measured over 30 days may have resulted in an underestimation of the associations between these variables. Finally, since this study is limited by the use of cross-sectional data, we cannot infer causality about the associations we observed. Longitudinal data are needed to investigate reciprocal relationships in key variables. In summary, this study identified correlates of methamphetamine-dealing behavior that could represent barriers to participation in drug treatment and HIV prevention programs. Future studies should examine intensity of drug use, hostility, gender, and age in relation to treatment motivation and resistance among individuals who engage in methamphetamine-dealing behavior. This research was funded by grants T32 DA Dr. Strathdee and R01 MH Dr. Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper. As a library, NLM provides access to scientific literature. Am J Addict. Published in final edited form as: Am J Addict. Find articles by Shirley J Semple. Find articles by Steffanie A Strathdee. Find articles by Tyson Volkmann. Find articles by Jim Zians. Find articles by Thomas L Patterson. Issue date Nov. PMC Copyright notice. The publisher's version of this article is available at Am J Addict. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. With other adults who are not sexual partners. Injection drug use in past two months mean, SD. Number of days methamphetamine used in past 30 days mean, SD. Number of grams of methamphetamine used in past 30 days mean, SD. Psychological Characteristics. Sexual sensation-seeking mean, SD. Assertiveness in turning down drugs mean, SD. Days per month of methamphetamine use high frequency vs. Amount of methamphetamine used in the past 30 days high vs. Sexual sensation-seeking per unit increase.

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Official websites use. Share sensitive information only on official, secure websites. Antiretroviral therapy has been effective in suppressing HIV viral load and enabling people living with HIV to experience longer, more conventional lives. However, as people living with HIV are living longer, they are developing aging-related diseases prematurely and are more susceptible to comorbidities that have been linked to chronic inflammation. Coincident with HIV infection and aging, drug abuse has also been independently associated with gut dysbiosis, microbial translocation, and inflammation. Here, we hypothesized that injection drug use would exacerbate HIV-induced immune activation and inflammation, thereby intensifying immune dysfunction. Plasma immune profiles were characterized by immunoproteomics, and cellular immunophenotypes were assessed using mass cytometry. In conclusion, a comprehensive analysis of inflammatory mediators and cell immunophenotypes revealed remarkably similar patterns of immune dysfunction in HIV-infected individuals and in people who inject drugs with and without HIV-1 infection. Injection drug use IDU of opioids and synthetic opioids i. Moreover, chronic diseases such as diabetes, cardiovascular diseases, premature aging, and neurologic diseases seen in PLWH could further be enhanced due to IDU, coinfection, dysbiosis, and chronic inflammation. In this cross-sectional study, we investigated the potential synergistic impacts of chronic HIV infection and IDU on immune functions by comprehensively analyzing the inflammatory cytokines and mediators, as well as the immune cell population profiles between PLWH and PWID. Written informed consent was obtained from all study participants, and all study data were deidentified before analysis and publication. After completion, each participant is given recruitment coupons that they can pass out to people they know who qualify for the study. Those who are recruited through coupons are then given more coupons and recruitment spreads through the local community. Participants were eligible for an incentive for completing the survey and for each recruitment coupon that resulted in a new participant. Overall, most eligible participants who responded to solicitation i. We were unable to estimate the proportion of coupons that were not passed on to potential new participants i. At the study site after obtaining written informed consent and conducting the survey, we performed HIV rapid antibody tests cat. A portion of whole blood was reserved for mass cytometry staining. The Cytodelics whole-blood preservation kit was used to stabilize the stained whole blood for storage and shipping cat. Importantly, our study performed the staining of fresh whole blood prior to stabilization, freezing, and shipping in order to avoid any negative staining effects. Graphical representation of study design and methodology. Whole-blood samples were collected and partitioned into plasma while reserving some whole blood. The plasma was subjected to the Olink proximity extension assay with the Olink Target 96 inflammation panel. The reserved whole blood was heparin blocked and isotope labeled before stabilization, fixation, washing, and quantification on the mass cytometer at OMRF. Created with BioRender. MDIPA contains a standard panel of 30 antibodies that can identify 37 immune cell populations. Adding the T-cell expansion pack 1 allows further characterization of T-cell activation and exhaustion. Cytodelics Stabilizer was added to 2-mL cryovials ratio with whole blood and equilibrated to room temperature for 5 to 10 min. Finally, the stained whole blood was transferred from the MDIPA tube to the cryovials containing the Cytodelics Stabilizer, mixed by inverting 10 to 15 times, and incubated at room temperature for 10 min. The cells were fixed with fresh 1. The normalized FCS files were used for downstream analyses. The percentage of lineage parent was calculated for each cell population and used for downstream analysis i. GraphPad Prism v9. The well plate was sealed, frozen, and shipped to Olink on dry ice. HIV-1 plasma viral load was quantified as described previously. Statistical analysis was performed in GraphPad Prism v9. These analyses were performed in R, and results are provided in tabular format in the supplemental materials Supplementary Table 3. Finally, multivariable linear regression with main effects for HIV status, IDU status, and their interaction was performed with adjustment for the potential confounding variables discussed above. Due to the use of all observations in the study for these comparisons, the assumption of residual normality is more likely to hold due to the central limit theorem, whereas this was not the case in unadjusted pairwise comparisons. We did not correct the P values here for studying multiple outcomes since this analysis was exploratory in nature, which may limit the power to detect observed differences in outcomes as was done in previous studies. Continuous variables are shown as median with interquartile range and compared using Mann-Whitney tests. The P values are italicized and significant P values are bolded. The self-reported non-injection drug use NIDU characteristics, treatment program history, and the results of urine toxicology tests performed at the time of blood sample collection were also compared between the groups Table 2. Injectors were more likely to have engaged in NIDU in the past 12 mo and to have participated in drug treatment programs than non-injectors Table 2. Finally, the self-reported use of multiple non-injection and injection drugs was analyzed for common combinations of drugs and visualized using heatmaps of the row percentages Supplementary Fig. For example, 1 of 38 speedball injectors 2. The most frequently reported non-injection drug was alcohol Supplementary Fig. Buprenorphine and alcohol were the most frequently co-occurring substances; of the 22 individuals who reported using buprenorphine through non-injection routes, Drug abuse has been shown to affect the levels of isolated cytokines in various studies, 16 — 18 , 21 , 22 but no study in humans has comprehensively investigated the extent to which IDU affects peripheral immune soluble inflammatory mediators. To evaluate differentials in plasma inflammatory profiles between injectors and non-injectors, we employed an established Olink proximity extension assay Target 96 Inflammation Panel; Olink Bioscience AB Fig. Finally, outlier samples were not detected. Exploratory PCA of inflammatory mediators and cellular immunophenotypes. In each case, the input data were standardized and centered. Studies to define the impact of IDU on the immune cell populations have focused on limited cell lineages. To develop a more comprehensive appreciation of how IDU alters peripheral immune cell phenotypes, we employed a mass cytometry panel of 36 isotopically defined mass markers to detect 47 immune cell populations, including granulocytes, in a single assay MDIPA; Fluidigm Fig. Surprisingly, this group included the exhausted T-cell subsets. This HIV association was not observed in the remaining excluded populations. We calculated the percentage of lineage parent i. Then, we applied PCA, and outliers were not detected Fig. Data sets for both inflammatory mediators and cellular immunophenotypes were merged for 59 participants, and PCA was applied Fig. Since the merged data set provided the best group segregation, we projected the PCA results in 3 dimensions Supplementary Fig. High variation between samples within groups and lack of tight clustering highlight the heterogeneity intrinsic to hard-to-reach human populations in a non-clinical setting. To ensure that potentially confounding demographic differences between groups Table 1 were not immunologically confounding factors, adjustment for age, homelessness, gender, marital status, employment status, and education was performed as described in the Materials and Methods and applied to all downstream analyses. Nevertheless, pairwise comparisons are needed to elucidate finer resolution differences between the groups and identify any potential additivity or synergy between HIV infection and IDU. In this confounder-adjusted analysis, 34 of 74 detectable inflammatory mediators were significant in at least 1 comparison. C GO enrichment analysis was performed for the inflammatory mediators with significant interaction effects in B, and the most specific subclass of the hierarchical ontology cluster is shown. To investigate the functional roles of these cytokines, we performed GO enrichment analysis Fig. While these GO enrichments and interaction effects are significant, they have small coefficient estimates i. We would therefore caution against overinterpretation. Because it was anticipated that different types of drugs abused and the frequency of use could differentially affect inflammatory profiles, we also investigated the associations of inflammatory mediators with drug use parameters collected during the study surveys Table 2 , Table 3. Nine inflammatory mediators correlated with the extent of polysubstance abuse evident in the urine test Supplementary Fig. These results indicate that the number of drugs abused can additionally influence plasma inflammatory mediator profiles. EM, effector memory; TE, terminal effector. Surprisingly, significant differences in the neutrophil and monocyte populations were not detected, contrary to what was expected since injectors would likely have increased exposure to pathogens. Thus, we employed an unbiased clustering algorithm of our live, singlet population. No global cell population differences were detected between our cohorts using this strategy Supplementary Fig. Further, no cell populations had a statistically significant correlation with the number of positive drugs in urine tests Supplementary Fig. Like the soluble mediators, there were significant interaction effects, but the coefficient estimates i. Thus, the biological significance of these subtle synergies is unclear. Overall, these data suggest that HIV has a larger effect on the peripheral immune cell populations than IDU but only a marginal synergistic effect in the context of IDU. Although previous studies have analyzed aspects of the effects of HIV and IDU on the immune system, this study, to our knowledge, provides the most comprehensive peripheral immune profiling data set available on PWID. Furthermore, this study focused on a unique population of Puerto Rican PWID and PLWH for whom the potential impacts of both insults on immune dysfunction have not been previously analyzed. Despite their significance, these interaction effects were accompanied by weak coefficient estimates, reinforcing the subtlety of any potential synergy. Moreover, the considerable differences in inflammatory mediators between PLWH and PWID vs controls did not translate into notable changes in cell phenotypes, and only weak to moderate correlations were noted between cell phenotypes and their associated inflammatory mediators Supplementary Fig. This is further reinforced by the lack of concordance between inflammatory mediators and cell populations with significant HIV, IDU, or interaction effects Fig. The inflammatory mediators may be originating from tissue-resident cells i. The effects of HIV infection and injection drug use on the peripheral immune repertoire. The upregulated cytokines are shown in the cloud Venn diagram for HIV infection, injection drug use, and those that are in common. The upregulated cytokines and dysregulated cell populations with significant interaction effects synergy between HIV infection and injection drug use are shown. The smaller text size indicates a less significant effect, while the larger text size indicates a more significant effect. Albeit through potentially different mechanisms, both drug abuse and HIV infection have been associated with gut dysbiosis and microbial translocation. Such translocation could explain the similarity in peripheral immune profiles. Microbial translocation can result from gut dysbiosis, weakening of the mucosal barrier, or an immune deficiency 35 and has been implicated in systemic inflammation. To our knowledge, this study is the first to apply Olink technology and mass cytometry to the study of immune dysfunction in PWID. The results are concordant with published studies using other assays in the context of drug abuse. Importantly, this did not translate into any functional innate or adaptive differences, 32 suggesting that although we detect differential cell population numbers, these are unlikely to translate into functional changes in the immune response. Further, in the study of abstinent cocaine users seeking treatment, Araos et al. Given the anticipation of high HCV prevalence and the aforementioned rates of self-reported HCV infection, we were unable to control for HCV infection status in our study and therefore did not seek to quantify HCV viral load. This supports the notion that our PWID have already been infected by HCV, which was likely not a confounding factor in the cytokine dysregulation detected in our study. This cross-sectional study has described the most comprehensive and contemporary data set on comparative immune profiling of PWID with and without HIV infection. While cause and effect cannot be established, this study has generated preliminary results using novel contemporary approaches upon which future studies can build. Finally, other recent studies have reported minimal and complex synergistic effects between HIV infection and heroin use. However, the disproportionality is representative of the natural populations. Additionally, it is important to note that the demographics of San Juan are not necessarily representative of the rest of Puerto Rico or the continental United States. It would be important for future studies to obtain a large sample from diverse regions and poverty levels, allowing the study to be more generalizable and evaluate the subtle differences between groups that may prove biologically or therapeutically relevant. There was also a higher proportion of males in our injectors group than non-injectors. Again, this is representative of the natural populations 6 and was accounted for in the confounder-adjusted analyses. However, when we removed the non-injectors with evidence of NIDU, our results remained largely the same. While many inflammatory mediators were significantly different between the mono- and dual-affected individuals and controls, there were very few differences between the mono- and dual-affected individuals themselves. We also identified subtle synergistic effects between HIV infection and IDU, but these effects may not be biologically relevant and did not translate into differences in peripheral immune cell phenotypes. Future studies with larger sample sizes and a focus on single drug-using populations would better elucidate how each drug of abuse affects the peripheral immune profile, and analysis of the gut microbiome, microbial translocation, and functional analysis of immune cells would paint a complete picture of how IDU and HIV infection, in combination, affect the immune system. Supplementary materials are available at Journal of Leukocyte Biology online. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. J Leukoc Biol. Published in final edited form as: J Leukoc Biol. Find articles by Sydney J Bennett. Find articles by Carmen Ana Davila. Find articles by Zahiraliz Reyes. Find articles by Kim Gocchi Carrasco. Find articles by Roberto Abadie. Find articles by M Caleb Marlin. Find articles by Marci Beel. Find articles by Andrew G Chapple. Find articles by Samodha Fernando. Find articles by Joel M Guthridge. Find articles by Kathy S Chiou. Find articles by Kirk Dombrowski. Find articles by John T West. Find articles by Charles Wood. Author contributions J. PMC Copyright notice. The publisher's version of this article is available at J Leukoc Biol. Open in a new tab. Conflict of interest statement. None declared. Supplementary material Supplementary materials are available at Journal of Leukocyte Biology online. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. 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