Purpose Investigate whether characteristics of geographic areas are associated with condomless sex and injection-related risk behavior among racial/ethnic groups of people who inject drugs (PWID) in the United States. Methods PWID were recruited from 19 metropolitan statistical areas for 2009 National HIV Behavioral Surveillance. Administrative data described ZIP codes, counties, and metropolitan statistical areas where PWID lived. Multilevel models, stratified by racial/ethnic groups, were used to assess relationships of place-based characteristics to condomless sex and injection-related risk behavior (sharing injection equipment). Results Among black PWID, living in the South (vs. Northeast) was associated with injection-related risk behavior (adjusted odds ratio [AOR] = 2.24, 95% confidence interval [CI]  = 1.21–4.17; P =.011), and living in counties with higher percentages of unaffordable rental housing was associated with condomless sex (AOR = 1.02, 95% CI = 1.00–1.04; P =.046). Among white PWID, living in ZIP codes with greater access to drug treatment was negatively associated with condomless sex (AOR = 0.93, 95% CI = 0.88–1.00; P =.038). Conclusions Policies that increase access to affordable housing and drug treatment may make environments more conducive to safe sexual behaviors among black and white PWID. Future research designed to longitudinally explore the association between residence in the south and injection-related risk behavior might identify specific place-based features that sustain patterns of injection-related risk behavior.

Objective: Opening Doors to Recovery (ODR) is a community navigation and recovery support model created in southeast Georgia by diverse, collaborative stakeholders. Following promising results from a quasi-experimental study, this randomized controlled trial hypothesized that, among patients with serious mental illnesses being discharged from inpatient psychiatric settings, compared to those randomized to traditional case management (CM) services, those randomized to ODR would have (1) lower likelihood of hospitalization, fewer hospitalizations, and fewer inpatient days; (2) lower likelihood of arrest, fewer arrests, and longer time to arrest; and, secondarily, (3) greater housing satisfaction and housing stability; and (4) higher scores on several scales measuring recovery-related constructs. Methods: 240 individuals with Structured Clinical Interview for DSM-5 Disorders-based psychotic or mood disorders, functional impairment, and repeated hospitalizations were randomized (December 2014 to June 2018) to ODR or CM. Hospitalization and arrest data were collected from State agencies after 12 months, and housing- and recovery-related measures were collected in person, longitudinally at 4, 8, and 12 months. Intention-to-treat analyses were conducted. Effects of dropout were accounted for, and sensitivity analyses were run. Results: ODR was associated with fewer days hospitalized (RR = 0.86, P = .001), a lower incidence of arrests (OR = 0.35, P < .0005), and longer time to arrest (HR = 0.42, P = .001). In addition, measures of housing satisfaction (Cohen d = 0.45) and recovery (Cohen d = 0.33) were significantly more improved in ODR patients compared to CM patients. Conclusions: The ODR model appears to have advantages over more traditional CM services and could fill a gap in the service array. Studying the mediators of success, cost benefit, dissemination, fidelity, and financing of the model is warranted. Trial Registration: ClinicalTrials.gov identifier: NCT04612777.

Background: Although a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treatment outcomes. To the best of our knowledge, this is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder. Methods: Eligible participants (n = 60) had a primary diagnosis of major depressive disorder and were assigned to either escitalopram or cognitive behavioral therapy based on fluorodeoxyglucose positron emission tomography activity in the right anterior insula. The overall study remission rate after 12 weeks of treatment, based on the end point Hamilton Depression Rating Scale score, was then examined for futility and benefit of the strategy. Results: Remission rates demonstrated lack of futility at the end of stage 1 (37%, 10/27), and the study proceeded to stage 2. After adjustment for the change in stage 2 sample size, the complete remission rate did not demonstrate evidence of benefit (37.7%, 95% confidence interval, 26.3%–51.4%, p = .38). However, total remission rates (complete and partial remission) did reach significance in post hoc analysis (49.1%, 95% confidence interval, 37.6%–60.7%, p = .020). Conclusions: The study shows some evidence for a role of the right anterior insula in the clinical choice of major depressive disorder monotherapy. The effect size, however, is insufficient for the use of insula activity as a sole predictive biomarker of remission. The study also demonstrates the logistical difficulties in establishing clinical utility of biomarkers.

Background Housing instability has been associated with poor health outcomes among people who inject drugs (PWID). This study investigates the associations of local-level housing and economic conditions with homelessness among a large sample of PWID, which is an underexplored topic to date. Methods PWID in this cross-sectional study were recruited from 19 large cities in the USA as part of National HIV Behavioral Surveillance. PWID provided self-reported information on demographics, behaviours and life events. Homelessness was defined as residing on the street, in a shelter, in a single room occupancy hotel, or in a car or temporarily residing with friends or relatives any time in the past year. Data on county-level rental housing unaffordability and demand for assisted housing units, and ZIP code-level gentrification (eg, index of percent increases in non-Hispanic white residents, household income, gross rent from 1990 to 2009) and economic deprivation were collected from the US Census Bureau and Department of Housing and Urban Development. Multilevel models evaluated the associations of local economic and housing characteristics with homelessness. Results Sixty percent (5394/8992) of the participants reported homelessness in the past year. The multivariable model demonstrated that PWID living in ZIP codes with higher levels of gentrification had higher odds of homelessness in the past year (gentrification: adjusted OR=1.11, 95% CI=1.04 to 1.17). Conclusions Additional research is needed to determine the mechanisms through which gentrification increases homelessness among PWID to develop appropriate community-level interventions.

Background Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depression. Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone (CRH)-containing circuits are involved in the pathophysiology of the disease. This Phase II trial aims to evaluate the efficacy of a CRH type 1 receptor (CRHR1) antagonist in the treatment of PTSD. Methods/design Currently untreated adult women, ages 18 to 65 years, with a primary psychiatric diagnosis of PTSD of at least 3 months’ duration, are being enrolled in a parallel-group, double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of GSK561679, a novel CRHR1 receptor antagonist. GSK561679 (or matching placebo) is prescribed at a fixed dose of 350 mg nightly for six weeks. The primary trial hypothesis is that GSK561679 will reduce symptoms of PTSD, as measured by the Clinician-Administered PTSD Scale (CAPS), significantly more than placebo after six weeks of treatment. Putative biological markers of PTSD which may influence treatment response are measured prior to randomization and after five weeks’ exposure to the study medication, including: fear conditioning and extinction using psychophysiological measures; variants of stress-related genes and gene expression profiles; and indices of HPA axis reactivity. In addition, the impact of PTSD and treatment on neuropsychological performance and functional capacity are assessed at baseline and after the fifth week of study medication. After completion of the six-week double blind treatment period, subjects enter a one-month follow-up period to monitor for sustained response and resolution of any adverse effects. Discussion Considerable preclinical and human research supports the hypothesis that alterations in central nervous system CRH neuronal activity are a potential mediator of PTSD symptoms. This study is the first to assess the efficacy of a specific antagonist of a CRH receptor in the treatment of PTSD. Furthermore, the biological and neuropsychological measures included in this trial will substantially inform our understanding of the mechanisms of PTSD.

Introduction: Adolescents living with perinatally acquired HIV have low rates of retention in care and viral suppression after the transition from paediatric to adult care. In this study, we developed and validated a tool to identify adolescent transition readiness. Methods: We developed the HIV Adolescent Readiness for Transition Scale (HARTS) from June 2016 to May 2019 by iteratively adapting existing transition readiness scales for other chronic illnesses by conducting focus groups with 11 healthcare providers and 20 adolescents in South Africa. We administered a preliminary questionnaire to 131 adolescents to determine psychometric properties and assess test–retest variability. We used confirmatory factor analysis to verify the proposed scale structure using the underlying variable approach. We correlated responses to self-described transition readiness and age using linear regression. We subsequently validated the scale by prospectively administering it to 199 adolescents in a second South African setting before their transition. We then used multivariable logistic regression to assess the effects of the HARTS and relevant socio-behavioural covariates on viral suppression one year after transition. Results: We identified four domains relevant to transition readiness: disclosure, health navigation, self-advocacy and health literacy. Fifteen questions with a significant factor loading of 0.3 to 0.9 were identified. No significant test–retest variability was seen among 10% of participants. Positive correlations with self-described transition readiness were significant with the overall HARTS and domains of health navigation, self-advocacy and health literacy. In the prospective analysis, for adolescents not using drugs, each 10-point increase in the HARTS was associated with 0.62 odds of viral failure (95% CI 0.45 to 0.86; p = 0.004). The individual domains of self-advocacy (AOR 0.56; 95% CI 0.33 to 0.94; p = 0.029), disclosure (AOR 0.02; 95% CI 0.01 to 0.25; p = 0.002), health navigation (AOR 0.51; 95%CI 0.25 to 1.02; p = 0.056) and health literacy (AOR 0.37; 95% CI 0.10 to 1.30; p = 0.121) were associated with viral failure adjusting for age at antiretroviral therapy initiation, ART regimen, sex, disclosure status, and alcohol use in both analyses. Conclusions: The HARTS is a validated scale that can be used to identify which adolescents may require additional interventions prior to transitioning to adult care to improve viral suppression after transition.

Background A reliable and meaningful quantitative index of success is paramount in the trial of any new treatment. However, existing methods for defining response and remission for treatments tested for psychiatric disorders are limited in that they often minimize the variance in change over time among individual patients and generally use arbitrarily chosen levels of functioning at specified times during treatment. Purpose To suggest and determine the properties of an alternative measure of treatment success, the Illness Density Index (IDI), that may be more sensitive to fluctuations in symptoms over the course of treatment compared to existing measures. Methods We examined data from 64 depressed patients with multiple assessments of the Hamilton Depression Rating Scale (HDRS) over 12 weeks of randomized treatment in order to compare and contrast varying numerical definitions of response and remission, including percent change and linear slope over time. Results Examination of the indices comparing the within-sample rank of individual patients revealed that these indices agree in cases where patients have little or no response as well as clear and sustained response, while they differ in patients who have a slow (or late) response as well as relapse during the treatment course. Limitations The measure may not be useful for all types of studies, especially short-term treatment trials. Conclusions The IDI is highly correlated with both categorical (e.g., remission) and continuous (e.g., percent change) definitions of treatment success. Furthermore, it differentiates certain trajectories of change that current definitions do not. Thus, the proposed index may be a valuable addition to current measures of efficacy, especially when trying to identify biological substrates of illness or predictors of long-term outcome.

Background: Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV-induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency. Methods: Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4+ T-cell (%HLA-DR+/ CD38+) and Treg (%CD4+CD25+FoxP3+) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway. Results: Lifetime IPV was associated with increased CD4+ activation (r = 0.331, P = 0.004), a shift in CD4+ phenotype from naïve to effector memory (r = 0.343, P = 0.003), and a decrease in naive (%HLA-DR+/CD45RA-) Treg frequency (r = -0.337, P = 0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4+ activation (P = 0.004 and P = 0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant (P = 0.012). Alcohol use and depression were identified as potential pathway moderators. Conclusion: Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway.

Objectives: Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. Methods: We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. Results: Escalation of premorbid use in the 5 years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR = 3.6, p < 0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR = 2.2, p < 0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (= 0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. Conclusions: These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations.

Introduction We analyzed relationships between place characteristics and being HIV-negative among black, Latino, and white people who inject drugs (PWID) in the US. Methods Data on PWID (N = 9077) were from the Centers for Disease Control and Prevention's 2009 National HIV Behavioral Surveillance. Administrative data were analyzed to describe the 968 ZIP codes, 51 counties, and 19 metropolitan statistical areas (MSAs) where they lived. Multilevel multivariable models examined relationships between place characteristics and HIV status. Exploratory population attributable risk percents (e-PAR %s) were estimated. Results Black and Latino PWID were more likely to be HIV-negative if they lived in less economically disadvantaged counties, or in MSAs with less criminal-justice activity (i.e., lower drug-related arrest rates, lower policing/corrections expenditures). Latino PWID were more likely to be HIV-negative in MSAs with more Latino isolation, less black isolation, and less violent crime. E-PAR%s attributed 8-19% of HIV cases among black PWID and 1-15% of cases among Latino PWID to place characteristics. Discussion Evaluations of structural interventions to improve economic conditions and reduce drug-related criminal justice activity may show evidence that they protect black and Latino PWID from HIV infection.