Strategies of Managing Repeated Measures: Using Synthetic Random Forest to Predict HIV Viral Suppression Status Among Hospitalized Persons with HIV.

The HIV/AIDS epidemic remains a major public health concern since the 1980s; untreated HIV infection has numerous consequences on quality of life. To optimize patients' health outcomes and to reduce HIV transmission, this study focused on vulnerable populations of people living with HIV (PLWH) and compared different predictive strategies for viral suppression using longitudinal or repeated measures. The four methods of predicting viral suppression are (1) including the repeated measures of each feature as predictors, (2) utilizing only the initial (baseline) value of the feature as predictor, (3) using the last observed value as the predictors and (4) using a growth curve estimated from the features to create individual-specific prediction of growth curves as features. This study suggested the individual-specific prediction of the growth curve performed the best in terms of lowest error rate on an independent set of test data.

Temporal assessment of lesion morphology on radiological images beyond lesion volumes-a proof-of-principle study.

OBJECTIVES: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA). METHODS: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network. RESULTS: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network. CONCLUSIONS: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. KEY POINTS: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation.

Contribution of Risk Factors to the Development of Coronary Atherosclerosis as Confirmed via Coronary CT Angiography: A Longitudinal Radiomics-based Study.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Cardiovascular risk factors and illicit drug use may have a more profound effect on coronary atherosclerosis progression in people living with HIV.

OBJECTIVES: To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. METHODS: We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. RESULTS: There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm3/year vs. 4.9 [IQR: 1.5-18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm3/year vs. 0.2 [IQR: 0.0-0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm3/year vs. 0.1 [IQR: 0.0-3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm3, CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm3, CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm3, CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). CONCLUSIONS: The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. KEY POINTS: • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Patterns of Substance Use and Arrest Histories Among Hospitalized HIV Drug Users: A Latent Class Analysis.

Using baseline data from the NIDA Clinical Trials Network 0049 study (Project HOPE), we performed latent class analyses (LCA) to identify discrete classes, or clusters, of people living with HIV (PLWH) based on their past year substance use behaviors and lifetime arrest history. We also performed multinomial logistic regressions to identify key characteristics associated with class membership. We identified 5 classes of substance users (minimal drug users, cocaine users, substantial cocaine/hazardous alcohol users, problem polysubstance users, substantial cocaine/heroin users) and 3 classes of arrest history (minimal arrests, non-drug arrests, drug-related arrests). While several demographic variables such as age and being Black or Hispanic were associated with class membership for some of the latent classes, participation in substance use treatment was the only covariate that was significantly associated with membership in all classes in both substance use and arrest history LCA models. Our analyses reveal complex patterns of behaviors among substance using PLWH and suggest that HIV intervention strategies may need to take into consideration such nuanced differences to better inform future studies and program implementation.

Examining the Efficacy of HIV Risk-Reduction Counseling on the Sexual Risk Behaviors of a National Sample of Drug Abuse Treatment Clients: Analysis of Subgroups.

HIV counseling with testing has been part of HIV prevention in the U.S. since the 1980s. Despite the long-standing history of HIV testing with prevention counseling, the CDC released HIV testing recommendations for health care settings contesting benefits of prevention counseling with testing in reducing sexual risk behaviors among HIV-negatives in 2006. Efficacy of brief HIV risk-reduction counseling (RRC) in decreasing sexual risk among subgroups of substance use treatment clients was examined using multi-site RCT data. Interaction tests between RRC and subgroups were performed; multivariable regression evaluated the relationship between RRC (with rapid testing) and sex risk. Subgroups were defined by demographics, risk type and level, attitudes/perceptions, and behavioral history. There was an effect (p < .0028) of counseling on number of sex partners among some subgroups. Certain subgroups may benefit from HIV RRC; this should be examined in studies with larger sample sizes, designed to assess the specific subgroup(s).

Effect of Patient Navigation With or Without Financial Incentives on Viral Suppression Among Hospitalized Patients With HIV Infection and Substance Use: A Randomized Clinical Trial.

IMPORTANCE: Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates. OBJECTIVE: To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients. DESIGN, SETTING, AND PARTICIPANTS: From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months. INTERVENTIONS: Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was HIV viral suppression (≤200 copies/mL) relative to viral nonsuppression or death at the 12-month follow-up. RESULTS: Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249 patients (34.1%) in the usual-treatment group experienced treatment success compared with 89 of 249 patients (35.7%) in the navigation-only group for a treatment difference of 1.6% (95% CI, -6.8% to 10.0%; P = .80) and compared with 98 of 254 patients (38.6%) in the navigation-plus-incentives group for a treatment difference of 4.5% (95% CI -4.0% to 12.8%; P = .68). The treatment difference between the navigation-only and the navigation-plus-incentives group was -2.8% (95% CI, -11.3% to 5.6%; P = .68). CONCLUSIONS AND RELEVANCE: Among hospitalized patients with HIV infection and substance use, patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual. These findings do not support these interventions in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01612169.

Uptake of HIV testing in substance use disorder treatment programs that offer on-site testing.

Increasing rates of HIV testing within substance use disorder (SUD) treatment clients is an important public health strategy for reducing HIV transmission rates. The present study examined uptake of HIV testing among 1,224 clients in five SUD treatment units that offered on-site testing in Florida, New York, and California. Nearly one-third (30 %) of the participants, who had not previously tested positive, reported not having been tested for HIV within the past 12 months. Women, African Americans, and injection drug users had a higher likelihood of having been tested within the past 12 months. The SUD treatment program was the most frequently identified location of participants' last HIV test. Despite the availability of free, on-site testing, a substantial proportion of clients were not tested, suggesting that strategies to increase uptake of testing should include addressing barriers not limited to location and cost.

Identifying patients with problematic drug use in the emergency department: results of a multisite study.

STUDY OBJECTIVE: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment. METHODS: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use. RESULTS: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score ≥ 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use. CONCLUSION: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs.

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland.

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association.Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis.Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14 µmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10 years, suggesting that extended cocaine use may have a substantial influence on cognitive performance.Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment.

Homocysteine modifies the association of coronary stenosis and HIV infection in an inner city African American population.

BACKGROUND AND AIMS: People with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis. In addition, plasma Hcy levels are higher in PWH than in individuals living without HIV. The aim of this study was to investigate whether Hcy levels influence the association between HIV and coronary stenosis in an inner city African American population. METHODS: African Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and February 2015, were included in this analysis. Participants underwent coronary CT angiography to evaluate the presence of coronary stenosis, defined as luminal stenosis >10%. Hcy was measured from stored serum samples. RESULTS: In this analysis, the median [IQR] age of the 664 participants was 56 [50-66] years; 68.1% were living with HIV and 43.1% were women. Elevated Hcy (>15 µmol/L) was more prevalent in those with coronary stenosis (23.3%, 95% CI: 18.4%-28.2%) than in those without coronary stenosis (13.1%, 95% CI: 9.7%-16.5%) (p = 0.0007), and HIV was associated with coronary stenosis in those participants with an elevated Hcy (Prevalence Ratio: 1.94, 95% CI: 1.04-3.64, p = 0.0038) and not in those with a Hcy ≤15 µmol/L (Prevalence Ratio: 1.02, 95% CI: 0.83-1.25, p = 0.87). CONCLUSIONS: Our data suggest an association between elevated Hcy levels (>15 µmol/L) and the prevalence of coronary stenosis in PWH from this inner city African American population.

Effect of risk-reduction counseling with rapid HIV testing on risk of acquiring sexually transmitted infections: the AWARE randomized clinical trial.

IMPORTANCE: To increase human immunodeficiency virus (HIV) testing rates, many institutions and jurisdictions have revised policies to make the testing process rapid, simple, and routine. A major issue for testing scale-up efforts is the effectiveness of HIV risk-reduction counseling, which has historically been an integral part of the HIV testing process. OBJECTIVE: To assess the effect of brief patient-centered risk-reduction counseling at the time of a rapid HIV test on the subsequent acquisition of sexually transmitted infections (STIs). DESIGN, SETTING, AND PARTICIPANTS: From April to December 2010, Project AWARE randomized 5012 patients from 9 sexually transmitted disease (STD) clinics in the United States to receive either brief patient-centered HIV risk-reduction counseling with a rapid HIV test or the rapid HIV test with information only. Participants were assessed for multiple STIs at both baseline and 6-month follow-up. INTERVENTIONS: Participants randomized to counseling received individual patient-centered risk-reduction counseling based on an evidence-based model. The core elements included a focus on the patient's specific HIV/STI risk behavior and negotiation of realistic and achievable risk-reduction steps. All participants received a rapid HIV test. MAIN OUTCOMES AND MEASURES: The prespecified outcome was a composite end point of cumulative incidence of any of the measured STIs over 6 months. All participants were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), herpes simplex virus 2, and HIV. Women were also tested for Trichomonas vaginalis. RESULTS: There was no significant difference in 6-month composite STI incidence by study group (adjusted risk ratio, 1.12; 95% CI, 0.94-1.33). There were 250 of 2039 incident cases (12.3%) in the counseling group and 226 of 2032 (11.1%) in the information-only group. CONCLUSION AND RELEVANCE: Risk-reduction counseling in conjunction with a rapid HIV test did not significantly affect STI acquisition among STD clinic patients, suggesting no added benefit from brief patient-centered risk-reduction counseling. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01154296.

Cocaine Use May Moderate the Associations of HIV and Female Sex with Neurocognitive Impairment in a Predominantly African American Population Disproportionately Impacted by HIV and Substance Use.

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population.

Implementing rapid HIV testing with or without risk-reduction counseling in drug treatment centers: results of a randomized trial.

OBJECTIVES: We examined the effectiveness of risk reduction counseling and the role of on-site HIV testing in drug treatment. METHODS: Between January and May 2009, we randomized 1281 HIV-negative (or status unknown) adults who reported no past-year HIV testing to (1) referral for off-site HIV testing, (2) HIV risk-reduction counseling with on-site rapid HIV testing, or (3) verbal information about testing only with on-site rapid HIV testing. RESULTS: We defined 2 primary self-reported outcomes a priori: receipt of HIV test results and unprotected anal or vaginal intercourse episodes at 6-month follow-up. The combined on-site rapid testing participants received more HIV test results than off-site testing referral participants (P<.001; Mantel-Haenszel risk ratio=4.52; 97.5% confidence interval [CI]=3.57, 5.72). At 6 months, there were no significant differences in unprotected intercourse episodes between the combined on-site testing arms and the referral arm (P=.39; incidence rate ratio [IRR]=1.04; 97.5% CI=0.95, 1.14) or the 2 on-site testing arms (P=.81; IRR=1.03; 97.5% CI=0.84, 1.26). CONCLUSIONS: This study demonstrated on-site rapid HIV testing's value in drug treatment centers and found no additional benefit from HIV sexual risk-reduction counseling.

Cocaethylene, simultaneous alcohol and cocaine use, and liver fibrosis in people living with and without HIV.

BACKGROUND: The simultaneous consumption of cocaine and alcohol results in the production of cocaethylene (CE) in the liver, a highly toxic metabolite. Prior research suggests that cocaine use contributes to liver disease and its concomitant use with alcohol may increase its hepatotoxicity, but studies in humans are lacking. We evaluated the role of cocaine, its simultaneous use with alcohol, and CE on liver fibrosis. METHODS: We performed a cross-sectional analysis of the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was determined via self-report, urine screen, and blood metabolites, using liquid chromatography with tandem mass spectrometry. Hazardous drinking was determined with the AUDIT-C and liver fibrosis with the Fibrosis-4 Index (FIB-4). RESULTS: Out of 649 participants included in this analysis, 281 (43.3%) used cocaine; of those, 78 (27.8%) had CE in blood. Cocaine users with CE had higher concentrations of cocaine metabolites in blood and were more likely to drink hazardously than cocaine users without CE and cocaine non-users. Overall, cocaine use was associated with liver fibrosis. CE in blood was associated with 3.17 (95% CI: 1.61, 6.23; p = 0.0008) times the odds of liver fibrosis compared to cocaine non-users, adjusting for covariates including HIV and HCV infection. The effect of CE on liver fibrosis was significantly greater than that of cocaine or alcohol alone. CONCLUSIONS: CE is a reliable marker of simultaneous use of cocaine and alcohol that may help identify individuals at risk of liver disease and aid in the prevention of its development or progression.

HIV, psychological resilience, and substance misuse during the COVID-19 pandemic: A multi-cohort study.

OBJECTIVE: The COVID-19 pandemic has dramatically impacted mental health, increasing rates of substance misuse. Resilience is a positive adaptation to stress that may act as a buffer against adverse mental health outcomes. Based on prior knowledge, we hypothesized that PLWH would display higher resilience than HIV-uninfected peers, and that high resilience would be associated with lower risk of substance misuse. METHODS: This analysis of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) included data from six USA cohorts that administered a COVID-19-related survey with a 3-month follow-up during May 2020 and March 2021. All data was self-reported. The Brief Resilience Scale and General Anxiety Disorder-7 were utilized. Primary analyses consisted of multivariate generalized linear mixed models with random intercepts using binary logistic regression. RESULTS: A total of 1430 participants completed both surveys, of whom 670 (46.9%) were PLWH. PLWH had lower odds of anxiety (OR=0.67, 95% CI: 0.51-0.89) and higher odds of high resilience (OR=1.21, 95% CI: 1.02-1.44) than HIV-uninfected participants, adjusted for covariates. The presence of anxiety was associated with higher risk of misuse of all substances. High resilience was associated with lower risk of anxiety and misuse of substances, adjusted for covariates. CONCLUSIONS: Psychological resilience was associated with lower risk of anxiety and substance misuse, potentially serving as a buffer against poor mental and behavioral health during the COVID-19 pandemic. Further research is needed to identify pathways of resilience in the context of substance misuse and comprehensive resilience-focused interventions.

Cocaine use associated gut permeability and microbial translocation in people living with HIV in the Miami Adult Study on HIV (MASH) cohort.

OBJECTIVE: Determine if cocaine use impacts gut permeability, promotes microbial translocation and immune activation in people living with HIV (PLWH) using effective antiretroviral therapy (ART). METHODS: Cross-sectional analysis of 100 PLWH (ART ≥6 months, HIV-RNA <200 copies/mL) from the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was assessed by self-report, urine screen, and blood benzoylecgonine (BE). Blood samples were collected to assess gut permeability (intestinal fatty acid-binding protein, I-FABP), microbial translocation (lipopolysaccharide, LPS), immune activation (sCD14, sCD27, and sCD163) and markers of inflammation (hs-CRP, TNF-α and IL-6). Multiple linear regression models were used to analyze the relationships of cocaine use. RESULTS: A total of 37 cocaine users and 63 cocaine non-users were evaluated. Cocaine users had higher levels of I-FABP (7.92±0.35 vs. 7.69±0.56 pg/mL, P = 0.029) and LPS (0.76±0.24 vs. 0.54±0.27 EU/mL, P<0.001) than cocaine non-users. Cocaine use was also associated with the levels of LPS (P<0.001), I-FABP (P = 0.033), and sCD163 (P = 0.010) after adjusting for covariates. Cocaine users had 5.15 times higher odds to exhibit higher LPS levels than non-users (OR: 5.15 95% CI: 1.89-13.9; P<0.001). Blood levels of BE were directly correlated with LPS (rho = 0.276, P = 0.028), sCD14 (rho = 0.274, P = 0.031), and sCD163 (rho = 0.250, P = 0.049). CONCLUSIONS: Cocaine use was associated with markers of gut permeability, microbial translocation, and immune activation in virally suppressed PLWH. Mitigation of cocaine use may prevent further gastrointestinal damage and immune activation in PLWH.

Reducing HIV-related risk behaviors among injection drug users in residential detoxification.

This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes.

Design of NIDA CTN Protocol 0047: screening, motivational assessment, referral, and treatment in emergency departments (SMART-ED).

BACKGROUND: Medical settings such as emergency departments (EDs) present an opportunity to identify and provide services for individuals with substance use problems who might otherwise never receive any form of assessment, referral, or intervention. Although screening, brief intervention, and referral to treatment models have been extensively studied and are considered effective for individuals with alcohol problems presenting in EDs and other medical settings, the efficacy of such interventions has not been established for drug users presenting in EDs. OBJECTIVES: This article describes the design of a NIDA Clinical Trials Network protocol testing the efficacy of an screening, brief intervention, and referral to treatment model in medical EDs, highlighting considerations that are pertinent to the design of other studies targeting substance use behaviors in medical treatment settings. METHODS: The protocol is described, and critical design decisions are discussed. RESULTS: Design challenges included defining treatment conditions, study population, and site characteristics; developing the screening process; choosing the primary outcome; balancing brevity and comprehensiveness of assessment; and selecting the strategy for statistical analysis. CONCLUSION: Many of the issues arising in the design of this study will be relevant to future studies of interventions for addictions in medical settings. SCIENTIFIC SIGNIFICANCE: Optimal trial design is critical to determining how best to integrate substance abuse interventions into medical care.

NIDA's Clinical Trials Network: an opportunity for HIV research in community substance abuse treatment programs.

BACKGROUND/OBJECTIVES: HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. RESULTS: While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. CONCLUSION/SIGNIFICANCE: While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.