Structural Discrimination against and Structural Support for Lesbian, Gay, and Bisexual People as a Predictor of Late HIV Diagnoses among Black Men who Have Sex with Men.

Black men who have sex with men (MSM) have been consistently reported to have the highest estimated HIV incidence and prevalence among MSM. Despite broad theoretical understanding that discrimination is a major social and structural determinant that contributes to disparate HIV outcomes among Black MSM, relatively little extant research has empirically examined structural discrimination against sexual minorities as a predictor of HIV outcomes among this population. The present study therefore examines whether variation in policies that explicitly discriminate against lesbian, gay, and bisexual (LGB) people and variation in policies that explicitly protect LGB people differentially predict metropolitan statistical-area-level variation in late HIV diagnoses among Black MSM over time, from 2008 to 2014. HIV surveillance data on late HIV diagnoses among Black MSM in each of the 95 largest metropolitan statistical areas in the United States, from 2008 to 2014, were used along with data on time-varying state-level policies pertaining to the rights of LGB people. Results from multilevel models found a negative relationship between protective/supportive laws and late HIV diagnoses among Black MSM, and a positive relationship between discriminative laws and late HIV diagnoses among Black MSM. These findings illuminate the potential epidemiological importance of policies pertaining to LGB populations as structural determinants of HIV outcomes among Black MSM. They suggest a need for scrutiny and elimination of discriminatory policies, where such policies are currently in place, and for advocacy for policies that explicitly protect the rights of LGB people where they do not currently exist.

Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area.

BACKGROUND: Recent studies underscore the significance of adopting a syndemics approach to study opioid misuse, overdose, hepatitis C (HCV) and HIV infections, within the broader context of social and environmental contexts in already marginalized communities. Social interactions and spatial contexts are crucial structural factors that remain relatively underexplored. This study examines the intersections of social interactions and spatial contexts around injection drug use. More specifically, we investigate the experiences of different residential groups among young (aged 18-30) people who inject drugs (PWID) regarding their social interactions, travel behaviors, and locations connected to their risk behaviors. By doing so, we aim to achieve a more comprehensive understanding of the multidimensional risk environment, thereby facilitating the development of informed policies. METHODS: We collected and examined data regarding young PWID's egocentric injection network and geographic activity spaces (i.e., where they reside, inject drugs, purchase drugs, and meet sex partners). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multidimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. RESULTS: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residential group on the West side of Chicago in Illinois where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages. Significant differences were observed in social network structures and travel behaviors: suburban participants had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections, while the urban group had the shortest travel distance for all types of risk activities. CONCLUSION: Distinct residential groups exhibit varying patterns of network interaction, travel behaviors, and geographical contexts related to their risk behaviors. Nonetheless, these groups share common concentrated risk activity spaces in a large outdoor urban drug market area, underscoring the significance of accounting for risk spaces and social networks in addressing syndemics within PWID populations.

Central projections from Johnston's organ in the locust: Axogenesis and brain neuroarchitecture.

Johnston's organ (Jo) acts as an antennal wind-sensitive and/or auditory organ across a spectrum of insect species and its axons universally project to the brain. In the locust, this pathway is already present at mid-embryogenesis but the process of fasciculation involved in its construction has not been investigated. Terminal projections into the fine neuropilar organization of the brain also remain unresolved, information essential not only for understanding the neural circuitry mediating Jo-mediated behavior but also for providing comparative data offering insights into its evolution. In our study here, we employ neuron-specific, axon-specific, and epithelial domain labels to show that the pathway to the brain of the locust is built in a stepwise manner during early embryogenesis as processes from Jo cell clusters in the pedicel fasciculate first with one another, and then with the two tracts constituting the pioneer axon scaffold of the antenna. A comparison of fasciculation patterns confirms that projections from cell clusters of Jo stereotypically associate with only one axon tract according to their location in the pedicellar epithelium, consistent with a topographic plan. At the molecular level, all neuronal elements of the Jo pathway to the brain express the lipocalin Lazarillo, a cell surface epitope that regulates axogenesis in the primary axon scaffold itself, and putatively during fasciculation of the Jo projections to the brain. Central projections from Jo first contact the primary axon scaffold of the deutocerebral brain at mid-embryogenesis, and in the adult traverse mechanosensory/motor neuropils similar to those in Drosophila. These axons then terminate among protocerebral commissures containing premotor interneurons known to regulate flight behavior.

Creation and Validation of a New Socio-built Environment Index Measure of Opioid Overdose Risk for Use in Both Non-urban and Urban Settings.

A great deal of literature has examined features of the physical built environment as predictors of opioid overdose and other substance use-related outcomes. Other literature suggests that social characteristics of settings are important predictors of substance use outcomes. However, there is a dearth of literature simultaneously measuring both physical and social characteristics of settings in an effort to better predict opioid overdose. There is also a dearth of literature examining built environment as a predictor of overdose in non-urban settings. The present study presents a novel socio-built environment index measure of opioid overdose risk comprised of indicators measuring both social and physical characteristics of settings - and developed for use in both urban and non-urban settings - and assesses its validity among 565 urban, suburban, and rural New Jersey municipalities. We found that this novel measure had good convergent validity, based on significant positive associations with a social vulnerability index and crime rates, and significant negative associations with a municipal revitalization index and high school graduation rates. The index measure had good discriminant validity, based on lack of association with three different racial isolation indices. Finally, our index measure had good health outcome-based criterion validity, based on significant positive associations with recent overdose mortality. There were no major differences between rural, suburban, and urban municipalities in validity analysis findings. This promising new socio-built environment risk index measure could improve ability to target and allocate resources to settings with the greatest risk, in order to improve their impact on overdose outcomes.

A Novel Index Measure of Housing-related Risk as a Predictor of Overdose among Young People Who Inject Drugs and Injection Networks.

Background: For people who inject drugs (PWID), housing instability due to decreasing housing affordability and other factors (e.g., loss of housing due to severed relational ties, evictions due to drug use) results in added pressure on an already vulnerable population. Research has shown that housing instability is associated with overdose risk among PWID. However, the construct of housing instability has often been operationalized as a single dimension (e.g., housing type, homelessness, transience). We propose a multi-dimensional measure of housing instability risk and examine its association with drug overdose to promote a more holistic examination of housing status as a predictor of overdose. Methods: The baseline data from a network-based, longitudinal study of young PWID and their networks living in metropolitan Chicago, Illinois was analyzed to examine the relationship between a housing instability risk index-consisting of five dichotomous variables assessing housing instability-and lifetime overdose count using negative binomial regression. Results: We found a significant positive association between the housing instability risk score and lifetime overdose count after adjusting for 12 variables. Conclusions: Our results support the practical utility of a multi-dimensional measure of housing instability risk in predicting overdose and highlight the importance of taking a holistic approach to addressing housing instability when designing interventions.

Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area.

Background: It is estimated that there are 1.5% US adult population who inject drugs in 2018, with young adults aged 18-39 showing the highest prevalence. PWID are at a high risk of many blood-borne infections. Recent studies have highlight the importance of employing the syndemic approach to study opioid misuse, overdose, HCV and HIV, along with the social and environmental contexts where these interrelated epidemics occur in already marginalized communities. Social interactions and spatial contexts are important structural factors that are understudied. Methods: Egocentric injection network and geographic activity spaces for young (aged 18-30) PWID and their injection, sexual, and social support network members (i.e., where reside, inject drugs, purchase drugs, and meet sex partners) were examined using baseline data from an ongoing longitudinal study (n=258). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multi-dimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. Results: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residence group on the West side of Chicago where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages (e.g., higher poverty rate, p <0.001). Significant ( p <0.01 for all) differences were observed in social network structures: suburban had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections. Conclusion: We identified concentrated risk activity spaces among PWID from urban, suburban, and transient groups in a large outdoor urban drug market area, which highlights the need for considering the role of risk spaces and social networks in addressing the syndemics in PWID populations.

Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated randomised, double-blind, placebo-controlled phase 2 study.

BACKGROUND: A gluten-free diet is insufficient to treat coeliac disease because intestinal injury persists and acute reactions with cytokine release follow gluten exposure. Nexvax2 is a specific immunotherapy using immunodominant peptides recognised by gluten-specific CD4+ T cells that might modify gluten-induced disease in coeliac disease. We aimed to assess the effects of Nexvax2 on gluten-induced symptoms and immune activation in patients with coeliac disease. METHODS: This was a randomised, double-blind, placebo-controlled phase 2 trial done at 41 sites (29 community, one secondary, and 11 tertiary centres) in the USA, Australia, and New Zealand. Patients with coeliac disease aged 18-70 years who had excluded gluten for at least 1 year, were HLA-DQ2.5 positive, and had a worsening of symptoms after an unmasked 10 g vital gluten challenge were eligible for inclusion. Patients were stratified by HLA-DQ2.5 status (HLA-DQ2.5 non-homozygous vs homozygous). Patients who were non-homozygous were centrally (ICON; Dublin, Ireland) randomly assigned (1:1) to receive subcutaneous Nexvax2 (non-homozygous Nexvax2 group) or saline (0·9% sodium chloride; non-homozygous placebo group) twice a week escalating from 1 µg to 750 µg during the first 5 weeks followed by 11 weeks of maintenance therapy at 900 µg per dose. The exploratory homozygous group was centrally randomly assigned (2:1) to receive Nexvax2 (homozygous Nexvax2 group) or placebo (homozygous placebo group); patients who were homozygous received the same dosage as those who were non-homozygous. The primary endpoint was change in coeliac disease patient reported outcomes (total gastrointestinal domain) from pretreatment baseline to the day of masked bolus 10 g vital gluten challenge given in week 14 analysed in the non-homozygous intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03644069. FINDINGS: Between Sept 21, 2018, and April 24, 2019, 383 volunteers were screened for inclusion, of whom 179 (47%; 133 [74%] women, 46 [26%] men; median age 41 years [IQR 33-55]) were randomly assigned. One (1%) of 179 patients was excluded from analysis due to misassignment of genotype. The non-homozygous Nexvax2 group included 76 patients, the non-homozygous placebo group included 78 patients, the homozygous Nexvax2 group included 16 patients, and the homozygous placebo group included eight patients. The study was discontinued after planned interim analysis of 66 patients who were non-homozygous. We report an unmasked post-hoc analysis of all available data for the primary endpoint and secondary symptom-based endpoints combining data from 67 (66 were assessed in the planned interim analysis for the primary endpoint). Mean change from baseline to day of first masked gluten challenge in total gastrointestinal score for the non-homozygous Nexvax2 group was 2·86 (SD 2·28) compared with 2·63 (2·07) for the non-homozygous placebo group (p=0·43). Adverse events were similar between all patients who received Nexvax2 and those who received placebo. Serious adverse events were reported in five (3%) of 178 patients (two [2%] of 92 who received Nexvax2 and three [4%] of 82 who received placebo). One patient in the non-homozygous Nexvax2 group had a serious adverse event that occurred during gluten challenge (left-sided mid-back muscle strain with imaging suggestive of partial left kidney infarction). Serious adverse events were reported for three (4%) of 78 patients in the non-homozygous placebo group (one each with exacerbation of asthma and appendicitis, and one who had forehead abscess, conjunctivitis, and folliculitis) and one (1%) patient in the non-homozygous Nexvax2 group developed a pulmonary embolism. The most frequent adverse events in all 92 patients who received Nexvax2 compared with all 86 patients who received placebo were nausea (44 [48%] of 92 patients who received Nexvax2 vs 29 (34%) of 86 patients who received placebo), diarrhoea (32 [35%] vs 25 [29%]), abdominal pain (31 [34%] vs 27 [31%]), headache 32 [35%] vs 20 [23%]), and fatigue (24 [26%] vs 31 [36%]). INTERPRETATION: Nexvax2 did not reduce acute gluten-induced symptoms. Masked bolus vital gluten challenge provides an alternative to extended gluten challenge in efficacy studies for coeliac disease. FUNDING: ImmusanT.

Network ethnic homophily and injection equipment sharing among Latinx and White non-Latinx people who inject drugs.

Latinx people who inject drugs (PWID) are less likely to engage in injection equipment sharing, but are more vulnerable to injection drug use (IDU)-related morbidity and mortality than Whites. Identifying subgroups of Latinx PWID who do engage in equipment sharing and likely bear the brunt of this health burden is a priority. Ethnic disparities may reflect contextual drivers, including injection networks. Latinx PWID with low ethnic homophily (the proportion of individuals with the same ethnic background) may be more likely to share equipment due to forced distancing from health-protective ethnocultural resources and power imbalances within injection networks. The current study offers a framework and examines how associations between network ethnic homophily and injection equipment sharing differ among 74 Latinx and 170 non-Latinx White PWID in the Chicagoland area (N = 244). Latinx had less homophilous than non-Latinx Whites (p <.001). Ethnic homophily was protective for equipment sharing among Latinx (OR = 0.17, 95%CI [0.77, 0.04], p = .02), but not non-Latinx Whites (OR = 1.66, 95%CI [0.40, 6.93], p = .49). Our findings implicate the need for targeted cultured interventions that focus on Latinx PWID who are more vulnerable to morbidity and mortality, potentially due to less access to ethnic peers.

Community-, network-, and individual-level predictors of uptake of medication for opioid use disorder among young people who inject drugs and their networks: A multilevel analysis.

BACKGROUND: Opioid use has been increasing at alarming rates over the past 15 years, yet uptake of medication for opioid use disorder (MOUD) remains low. Much of the research on individual characteristics predicting MOUD uptake is equivocal, and there is a dearth of research on setting-level and network-level characteristics that predict MOUD uptake. Towards a more holistic, multilevel understanding, we explore individual-level, network-level, and community-level characteristics associated with MOUD uptake. METHODS: Baseline data from a longitudinal study of young people who inject drugs and their injection and support network members living in Chicago (N = 165) was used to conduct cross-sectional multilevel logistic regression analyses to examine associations between MOUD uptake and a set of potential predictors at the individual-, network-, and community-levels that were chosen based on theoretical relevance or support from previous empirical studies. RESULTS: Stigma at both the individual and community levels was significantly associated with MOUD uptake (though in different directions). Greater individual-level stigma was associated with a higher likelihood of MOUD uptake, while having a more normatively stigmatizing community environment was associated with a lower likelihood of MOUD uptake. Using heroin and cocaine simultaneously and having a larger support network were associated with a greater likelihood of MOUD uptake. CONCLUSIONS: The present study's holistic, multilevel approach identified three individual-level characteristics, one network-level characteristic, and one community-level characteristic associated with MOUD uptake. However, more research is needed examining multilevel predictors, to help with developing interventions addressing barriers to MOUD use at multiple levels of influence.

Pilot Testing Two Versions of a Social Network Intervention to Increase HIV Testing and Case-finding among Men in South Africa's Generalized HIV Epidemic.

Locating undiagnosed HIV infections is important for limiting transmission. However, there is limited evidence about how best to do so. In South Africa, men have been particularly challenging to reach for HIV testing due, in part, to stigma. We pilot-tested two versions of a network-based case-finding and care-linkage intervention. The first, TRIP, asked "seeds" (original participants) to recruit their sexual and/or injection partners. The second, TRIPLE, aimed to circumvent some stigma-related issues by asking seeds to recruit anyone they know who might be at risk of being HIV-positive-unaware. We recruited 11 (18% male) newly diagnosed HIV-positive (NDP) seeds from two clinics in KwaZulu-Natal, South Africa and randomly assigned them to either TRIP or TRIPLE. Network members were recruited two steps from each seed. The TRIP arm recruited 12 network members; the TRIPLE arm recruited 62. Both arms recruited NDPs at higher rates than local clinic testing, with TRIP (50.0%) outperforming (p = 0.012) TRIPLE (14.5%). However, TRIPLE (53.2%) was far superior to clinics (27.8%) and to TRIP (25.0%) at recruiting men. Given challenges around testing and treating men for HIV in this context, these findings suggest that the TRIPLE expanded network-tracing approach should be tested formally among larger samples in multiple settings.

Toward a Theory of the Underpinnings and Vulnerabilities of Structural Racism: Looking Upstream from Disease Inequities among People Who Use Drugs.

Structural racism is increasingly recognized as a key driver of health inequities and other adverse outcomes. This paper focuses on structural racism as an "upstream" institutionalized process, how it creates health inequities and how structural racism persists in spite of generations of efforts to end it. So far, "downstream" efforts to reduce these health inequities have had little success in eliminating them. Here, we attempt to increase public health awareness of structural racism and its institutionalization and sociopolitical supports so that research and action can address them. This paper presents both a theoretic and an analytic approach to how structural racism contributes to disproportionate rates of HIV/AIDS and related diseases among oppressed populations. We first discuss differences in disease and health outcomes among people who use drugs (PWUD) and other groups at risk for HIV from different racial and ethnic populations. The paper then briefly analyzes the history of racism; how racial oppression, class, gender and other intersectional divisions interact to create health inequities; and how structural racism is institutionalized in ways that contribute to disease disparities among people who use drugs and other people. It examines the processes, institutions and other structures that reinforce structural racism, and how these, combined with processes that normalize racism, serve as barriers to efforts to counter and dismantle the structural racism that Black, indigenous and Latinx people have confronted for centuries. Finally, we discuss the implications of this analysis for public health research and action to undo racism and to enhance the health of populations who have suffered lifetimes of racial/ethnic oppression, with a focus on HIV/AIDS outcomes.

Egocentric network characteristics of people who inject drugs in the Chicago metro area and associations with hepatitis C virus and injection risk behavior.

BACKGROUND: Hepatitis C (HCV) infection has been rising in the suburban and rural USA, mainly via injection-based transmission. Injection and sexual networks are recognized as an important element in fostering and preventing risky behavior; however, the role of social support networks has received somewhat less attention. METHODS: Using baseline data from an ongoing longitudinal study, we examined the composition and structure of injection drug use (IDU), sex, and social support networks of young people who inject drugs (aged 18-30) and their injection network members. Lasso logistic regression was used to select a subset of network characteristics that were potentially important predictors of injection risk behaviors and HCV exposure. RESULTS: Several measures of IDU, sexual, and support network structure and composition were found to be associated with HCV exposure, receptive syringe sharing (RSS), and ancillary equipment sharing. Gender and sexual relationships were important factors for all risk behaviors. Support network characteristics were also important, notably including a protective effect of majority Hispanic support networks for RSS and HCV exposure. Both IDU network residence heterogeneity and support network geography were associated with injection equipment sharing. CONCLUSIONS: The associations of IDU and support network geography with equipment sharing highlight the need to extend harm reduction efforts beyond urban areas. Greater understanding of support network influences on risk behavior may provide important insights to strengthen the benefits of harm reduction. In considering the probability of HCV transmission, it is important to consider setting and network structures that promote propagation of risk.

Conceptualizing the Socio-Built Environment: An Expanded Theoretical Framework to Promote a Better Understanding of Risk for Nonmedical Opioid Overdose Outcomes in Urban and Non-Urban Settings.

Nonmedical opioid (NMO) use has been linked to significant increases in rates of NMO morbidity and mortality in non-urban areas. While there has been a great deal of empirical evidence suggesting that physical features of built environments represent strong predictors of drug use and mental health outcomes in urban settings, there is a dearth of research assessing the physical, built environment features of non-urban settings in order to predict risk for NMO overdose outcomes. Likewise, there is strong extant literature suggesting that social characteristics of environments also predict NMO overdoses and other NMO use outcomes, but limited research that considers the combined effects of both physical and social characteristics of environments on NMO outcomes. As a result, important gaps in the scientific literature currently limit our understanding of how both physical and social features of environments shape risk for NMO overdose in rural and suburban settings and therefore limit our ability to intervene effectively. In order to foster a more holistic understanding of environmental features predicting the emerging epidemic of NMO overdose, this article presents a novel, expanded theoretical framework that conceptualizes "socio-built environments" as comprised of (a) environmental characteristics that are applicable to both non-urban and urban settings and (b) not only traditional features of environments as conceptualized by the extant built environment framework, but also social features of environments. This novel framework can help improve our ability to identify settings at highest risk for high rates of NMO overdose, in order to improve resource allocation, targeting, and implementation for interventions such as opioid treatment services, mental health services, and care and harm reduction services for people who use drugs.

Economic Challenges and Behavioral and Mental Health Risks for Overdose during the COVID-19 Pandemic among People Who Inject Drugs.

People who inject drugs (PWID) are a population that disproportionately struggles with economic and mental health challenges. However, despite numerous reports of people globally experiencing new or exacerbated economic and/or mental health challenges during the COVID-19 pandemic, the literature on the effect of the pandemic on PWID and their risk for harm (e.g., overdose) remains sparse. The present study will describe reported changes during the pandemic in risk factors for drug overdose (including changes in mental health symptoms and care access) among PWID in Chicago, and it will examine associations between such risk factor changes and the experience of economic challenges during the pandemic. Participants from an ongoing longitudinal study of young PWID from the Chicago suburbs and their injection risk network members (N = 138; mean age = 28.7 years) were interviewed about changes in their experiences, substance use behavior, and mental health since the start of the COVID-19 pandemic. Bivariate cross tabulations were computed of each "overdose risk factor" with experiences of economic challenges during the pandemic. Fisher's Exact Tests were used to assess statistical significance. Adjusted logistic regression models were also conducted that controlled for sociodemographic characteristics, for time elapsed since the start of the pandemic, and for pre-pandemic income, homelessness, and injection frequency. Over half of our sample reported using alone more than usual during the pandemic, and over 40% reported using more than usual and/or buying drugs that were of a decreased purity or quality. Additionally, a large proportion of our sample (52.5% of those asked) reported more difficulty than usual accessing mental health care. Experiencing loss of a source of income during the pandemic was associated with using more drugs, using alone more, using a larger amount of drugs while using alone, wanting to stop using but being unable, and difficulty accessing mental health care. The preliminary associations found by the present study suggest that economic challenges or disruptions experienced during the pandemic are likely to increase risk for overdose among PWID experiencing such challenges, via changes in the above behaviors and/or conditions that are associated with risk for overdose. Intervention efforts should therefore be focused not only directly on overdose prevention, but also on assisting PWID with their economic challenges and helping them regain economic stability and access to services that may have been impeded by financial difficulty.

The stigma system: How sociopolitical domination, scapegoating, and stigma shape public health.

Stigma is a fundamental driver of adverse health outcomes. Although stigma is often studied at the individual level to focus on how stigma influences the mental and physical health of the stigmatized, considerable research has shown that stigma is multilevel and structural. This paper proposes a theoretical approach that synthesizes the literature on stigma with the literature on scapegoating and divide-and-rule as strategies that the wealthy and powerful use to maintain their power and wealth; the literatures on racial, gender, and other subordination; the literature on ideology and organization in sociopolitical systems; and the literature on resistance and rebellion against stigma, oppression and other forms of subordination. we develop a model of the "stigma system" as a dialectic of interacting and conflicting structures and processes. Understanding this system can help public health reorient stigma interventions to address the sources of stigma as well as the individual problems that stigma creates. On a broader level, this model can help those opposing stigma and its effects to develop alliances and strategies with which to oppose stigma and the processes that create it.

Trajectories of and disparities in HIV prevalence among Black, White, and Hispanic/Latino High Risk Heterosexuals in 89 U.S. Metropolitan statistical areas, 1992-2013.

PURPOSE: Estimates of HIV prevalence, and how it changes over time, are needed to inform action (e.g., resource allocation) to improve HIV-related public health. However, creating adequate estimates of (diagnosed and undiagnosed) HIV prevalence is challenging due to biases in samples receiving HIV testing and due to difficulties enumerating key risk populations. To our knowledge, estimates of HIV prevalence among high risk heterosexuals in the United States produced for geographic areas smaller than the entire nation have to date been only for single years and/or for single cities (or other single geographic locations). METHODS: The present study addresses these gaps by using multilevel modeling on multiple data series, in combination with previous estimates of HIV prevalence among heterosexuals from the extant literature, to produce annual estimates of HIV prevalence among high risk heterosexuals for each of 89 metropolitan statistical areas, from 1992 to 2013. It also produces estimates for these MSAs and years by racial/ethnic subgroup to allow for an examination of change over time in racial/ethnic disparities in HIV prevalence among high risk heterosexuals. RESULTS: The resulting estimates suggest that HIV prevalence among high risk heterosexuals has decreased steadily, on average, from 1992 to 2013. Examination of these estimates by racial/ ethnic subgroup suggests that this trend is primarily due to decreases among Black and Hispanic/Latino high risk heterosexuals. HIV prevalence among white high risk heterosexuals remained steady over time at around 1% during the study period. Although HIV prevalence among Black and Hispanic/Latino high risk heterosexuals was much higher (approximately 3.5% and 3.3%, respectively) than that among whites in 1992, over time these differences decreased as HIV prevalence decreased over time among these subgroups. By 2013, HIV prevalence among Hispanic/Latino high risk heterosexuals was estimated to be very similar to that among white high risk heterosexuals (approximately 1%), with prevalence among Black high risk heterosexuals still estimated to be almost twice as high. CONCLUSIONS: It is likely that as HIV incidence has decreased among heterosexuals from 1992 to 2013, mortality due to all causes has remained disparately high among racial/ethnic minorities, thereby outpacing new HIV cases. Future research should aim to empirically examine this by comparing changes over time in estimated HIV incidence among heterosexuals to changes over time in mortality and causes of death among HIV-positive heterosexuals, by racial/ethnic subgroup.

Sexually Transmitted Infection Epidemiology and Care in Rural Areas: A Narrative Review.

BACKGROUND: Although rural areas contain approximately 19% of the US population, little research has explored sexually transmitted infection (STI) risk and how urban-developed interventions may be suitable in more population-thin areas. Although STI rates vary across rural areas, these areas share diminishing access to screening and limited rural-specific testing of STI interventions. METHODS: This narrative review uses a political ecology model of health and explores 4 domains influencing STI risk and screening: epidemiology, health services, political and economic, and social. Articles describing aspects of rural STI epidemiology, screening access and use, and intervention utility within these domains were found by a search of PubMed. RESULTS: Epidemiology contributes to risk via multiple means, such as the presence of increased-risk populations and the at-times disproportionate impact of the opioid/drug use epidemic. Rural health services are diminishing in quantity, often have lesser accessibility, and may be stigmatizing to those needing services. Local political and economic influences include funding decisions, variable enforcement of laws/statutes, and systemic prevention of harm reduction services. Social norms such as stigma and discrimination can prevent individuals from seeking appropriate care, and also lessen individual self-efficacy to reduce personal risk. CONCLUSIONS: Sexually transmitted infection in rural areas is significant in scope and facing diminished prevention opportunities and resources. Although many STI interventions have been developed and piloted, few have been tested to scale or operationalized in rural areas. By considering rural STI risk reduction within a holistic model, purposeful exploration of interventions tailored to rural environments may be explored.

A Sensitive Whole Blood Assay Detects Antigen-Stimulated Cytokine Release From CD4+ T Cells and Facilitates Immunomonitoring in a Phase 2 Clinical Trial of Nexvax2 in Coeliac Disease.

Improved blood tests assessing the functional status of rare gluten-specific CD4+ T cells are needed to effectively monitor experimental therapies for coeliac disease (CD). Our aim was to develop a simple, but highly sensitive cytokine release assay (CRA) for gluten-specific CD4+ T cells that did not require patients to undergo a prior gluten challenge, and would be practical in large, multi-centre clinical trials. We developed an enhanced CRA and used it in a phase 2 clinical trial ("RESET CeD") of Nexvax2, a peptide-based immunotherapy for CD. Two participants with treated CD were assessed in a pilot study prior to and six days after a 3-day gluten challenge. Dye-dilution proliferation in peripheral blood mononuclear cells (PBMC) was assessed, and IL-2, IFN-γ and IL-10 were measured by multiplex electrochemiluminescence immunoassay (ECL) after 24-hour gluten-peptide stimulation of whole blood or matched PBMC. Subsequently, gluten-specific CD4+ T cells in blood were assessed in a subgroup of the RESET CeD Study participants who received Nexvax2 (maintenance dose 900 µg, n = 12) or placebo (n = 9). The pilot study showed that gluten peptides induced IL-2, IFN-γ and IL-10 release from PBMCs attributable to CD4+ T cells, but the PBMC CRA was substantially less sensitive than whole blood CRA. Only modest gluten peptide-stimulated IL-2 release could be detected without prior gluten challenge using PBMC. In contrast, whole blood CRA enabled detection of IL-2 and IFN-γ before and after gluten challenge. IL-2 and IFN-γ release in whole blood required more than 6 hours incubation. Delay in whole blood incubation of more than three hours from collection substantially reduced antigen-stimulated IL-2 and IFN-γ secretion. Nexvax2, but not placebo treatment in the RESET CeD Study was associated with significant reductions in gluten peptide-stimulated whole blood IL-2 and IFN-γ release, and CD4+ T cell proliferation. We conclude that using fresh whole blood instead of PBMC substantially enhances cytokine secretion stimulated by gluten peptides, and enables assessment of rare gluten-specific CD4+ T cells without requiring CD patients to undertake a gluten challenge. Whole blood assessment coupled with ultra-sensitive cytokine detection shows promise in the monitoring of rare antigen-specific T cells in clinical studies.

Mental Health and Perceived Access to Care among People Who Inject Drugs in Athens, Greece.

Poor mental health among human immunodeficiency virus (HIV)-positive people who inject drugs (PWID) may contribute to stigma, and together they act as barriers to medical care. This analysis aims to examine factors associated with the mental health of PWID and their network contacts, and the association of poor mental health with the experience of HIV-related stigmatizing events, with HIV-related social support, and with perceived access to care. Data were collected during the Transmission Reduction Intervention Project (TRIP) conducted in Athens, Greece (2013-2015). PWID (n = 292; n = 122 HIV-positive) were interviewed both at baseline and follow-up. Items of depression, anxiety, and general positive affect subscales of the Mental Health Inventory were used to explore the psychological distress and well-being of participants at follow-up. Items of the Access to Care Scale were used to evaluate perceived access to medical care at baseline and follow-up. Linear regression showed that unemployment was positively related to depression (ß = 1.49, p = 0.019), while injecting drug use was a risk factor for a low general positive affect score (ß = -3.21, p = 0.015). Poor mental health was not linked to HIV-related stigma or social support. Positive perception of access to care was associated in multivariable analyses with low depression (ß = -0.22, p = 0.049). The perceived access to care score improved from baseline to follow-up (p = 0.019) and HIV-positive participants had a higher score than HIV-negative participants. Future interventions should include targets to improve the mental well-being of participants, reduce psychosocial distress, and minimize perceived barriers to accessing medical care.

Drug use-related stigma, safer injection norms, and hepatitis C infection among a network-based sample of young people who inject drugs.

BACKGROUND: Identifying risk for hepatitis C (HCV) infection is important for understanding recent increases in HCV incidence among young people who inject drugs (PWID) in suburban and rural areas; and for refining the targeting of effective HCV preventive interventions. Much of the extant research has focused on individual health behaviors (e.g., risky drug injection behaviors) as predictors of HCV infection. The present study examines two social factors (substance use-related stigma and injection-related social norms), and the interaction between these factors, as predictors of HCV infection. METHODS: Baseline data were used from an ongoing longitudinal study of young PWID (N = 279; mean age = 30.4 years) from the Chicago suburbs and their injection risk network members. Adjusted logistic regression models were used to examine relationships among substance use-related stigma, safer injection norms, and HCV infection. RESULTS: Despite a marginal bivariate association between less safe injection norms and HCV infection (OR = 0.74; 95 % CI[0.39, 1.02]; p = .071), a significant stigma X norms interaction (AOR = 0.68; 95 % CI[0.51, 0.90]) suggested that at high levels of stigma, probability of HCV infection was high regardless of injection norms. CONCLUSIONS: Findings suggest that social factors - specifically, substance use-related stigma and injection norms - are important predictors of HCV infection risk. The interaction found between these social factors suggests that intervening only to change injection norms or behaviors is likely insufficient to reduce risk for HCV infection in high-stigma settings or among high-stigma populations. Future research should develop and evaluate stigma-reduction interventions in combination with safer-injection interventions in order to maximize HCV risk reduction.