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The United States is in the fourth wave of the opioid epidemic marked by the increase in fentanyl and co‐occurring stimulant use related overdose deaths. Measures are needed to quickly diagnose opioid and stimulant use disorders, yet current traditional diagnostic assessments pose barriers to providing rapid diagnoses. This study aimed to (1) validate an updated version of the Rapid Opioid Dependence Screen (RODS) from DSM‐IV criteria for opioid dependence to the now DSM‐5 moderate‐to‐severe opioid use disorder, the Rapid Opioid Use Disorder Assessment (ROUDA); and (2) create and validate the Rapid Stimulant Use Disorder Assessment to DSM‐5 stimulant use disorder (RSUDA) when compared to the substance use disorder module from the DSM‐5 version of the Mini International Neuropsychiatric Interview. One‐hundred and fifty adults completed study assessments, 122 reported opioid misuse and 140 reported stimulant misuse within their lifetime. The ROUDA had a sensitivity of 82.5% (95% confidence interval [CI] 75.7, 89.2), specificity of 100.0% (95% CI: 100, 100), and strong internal consistency α= 0.94. The RSUDA had similarly high sensitivity (83.8%, 95% CI: 77.7, 89.9), specificity (91.4%, 95% CI: 86.8, 96.1), and internal consistency α= 0.87. The ROUDA and RSUDA are efficient and valid measures that can be administered in various settings by non‐clinical staff to rapidly diagnose opioid and stimulant use disorders and allow for immediate treatment and harm reduction interventions. The ROUDA and RSUDA are efficient and valid measures that can be administered by non‐clinicians to rapidly diagnose opioid and stimulant use disorders. The Rapid Opioid Dependence Screen has been updated to the Rapid Opioid Use Disorder Assessment (ROUDA) to identify those who meet DSM‐5 criteria for moderate to severe opioid use disorder.The Rapid Stimulant Use Disorder Assessment (RSUDA) is a new valid tool that can be administered quickly and easily in a variety of settings to identify those with a moderate to severe stimulant use disorder per DSM‐5 criteria.Both the ROUDA and RSUDA can be administered by clinical and non‐clinical personnel in a variety of settings, increasing the accessibility to opioid and/or stimulant use disorder diagnoses.Identifying those with opioid and/or stimulant use disorder can provide a reachable moment for education, harm reduction, and linkage to treatment. The Rapid Opioid Dependence Screen has been updated to the Rapid Opioid Use Disorder Assessment (ROUDA) to identify those who meet DSM‐5 criteria for moderate to severe opioid use disorder. The Rapid Stimulant Use Disorder Assessment (RSUDA) is a new valid tool that can be administered quickly and easily in a variety of settings to identify those with a moderate to severe stimulant use disorder per DSM‐5 criteria. Both the ROUDA and RSUDA can be administered by clinical and non‐clinical personnel in a variety of settings, increasing the accessibility to opioid and/or stimulant use disorder diagnoses. Identifying those with opioid and/or stimulant use disorder can provide a reachable moment for education, harm reduction, and linkage to treatment.

Background Previous research has shown gender differences with respect to entry into medication treatment of substance use disorders (SUDs), yet few have examined gender differences among participants consented to be treated with extended-release naltrexone (XR-NTX). Understanding gender differences is critical to developing interventions to overcome barriers to initiation of and retention on medication treatment for SUDs.Methods Data from two double-blind placebo-controlled trials of XR-NTX among persons with HIV and alcohol or opioid use disorders leaving the criminal justice system (CJS) were analyzed for gender differences among clinical characteristics, mental health, drug use severity, and other domains. The study that recruited persons with alcohol use disorder (AUD) was conducted from September 2010–February 2016 at two sites in Connecticut (CT), and the opioid use disorder (OUD) study was conducted from September 2010–March 2016 at three sites in CT and one site in Massachusetts.Results Baseline data were analyzed from 193 participants consented to be randomized to XR-NTX or placebo; 40 women and 153 men. Women were younger, had worse mental health severity, and were more likely to be diagnosed with cocaine use disorder. There were no statistical differences between men and women in the prescription of antiretroviral therapy (ART) or ART adherence.Conclusions Women had greater mental health severity and a higher prevalence of cocaine use as compared to men, both of which are known to be barriers to engagement and retention on medication treatment for alcohol and opioid use disorders. For women with CJS involvement and living with HIV and SUDs, understanding factors that may affect initiation and retention on medication treatment of SUDs are necessary to improve treatment outcomes in women.

AbstractBackground:Previous research has shown gender differences with respect to entry into medication treatment of substance use disorders (SUDs), yet few have examined gender differences among participants consented to be treated with extended-release naltrexone (XR-NTX). Understanding gender differences is critical to developing interventions to overcome barriers to initiation of and retention on medication treatment for SUDs. Methods: Data from two double-blind placebo-controlled trials of XR-NTX among persons with HIV and alcohol or opioid use disorders leaving the criminal justice system (CJS) were analyzed for gender differences among clinical characteristics, mental health, drug use severity, and other domains. The study that recruited persons with alcohol use disorder (AUD) was conducted from September 2010–February 2016 at two sites in Connecticut (CT), and the opioid use disorder (OUD) study was conducted from September 2010–March 2016 at three sites in CT and one site in Massachusetts. Results: Baseline data were analyzed from 193 participants consented to be randomized to XR-NTX or placebo; 40 women and 153 men. Women were younger, had worse mental health severity, and were more likely to be diagnosed with cocaine use disorder. There were no statistical differences between men and women in the prescription of antiretroviral therapy (ART) or ART adherence. Conclusions: Women had greater mental health severity and a higher prevalence of cocaine use as compared to men, both of which are known to be barriers to engagement and retention on medication treatment for alcohol and opioid use disorders. For women with CJS involvement and living with HIV and SUDs, understanding factors that may affect initiation and retention on medication treatment of SUDs are necessary to improve treatment outcomes in women.

Although the WHO strategy aims to eliminate the hepatitis C virus (HCV) as a public health threat by 2030, national strategies are variable worldwide. This study aimed to assess the establishment of different policies and strategies to eliminate HCV in the Americas.

Over 1.2 million Americans aged 13 and older have been diagnosed with HIV. While HIV incidence has been declining since 2017, the risk of HIV acquisition and transmission persists among persons who use drugs via injection drug use and unprotected sexual intercourse associated with substance use. Untreated substance use disorder is associated with poor adherence to HIV antiretroviral therapy, poor HIV outcomes, and increased risk for HIV acquisition. Herein, we describe the intertwined syndemic of HIV and substance use disorder, as well as treatment strategies and evidence-based public health efforts to engage and retain persons who use drugs into care.

In the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system.

Background: Medication treatment for opioid use disorder (OUD) (MOUD; buprenorphine and methadone) reduces opioid use and overdose. Discontinuation of MOUD can quickly lead to relapse, overdose and death. Few persons who initiate MOUD are retained on treatment, thus it is critical to identify factors associated with retention. Methods: Evaluated data was from an ongoing prospective cohort study of adults aged 18 or older with DSM-5 moderate to severe OUD seeking MOUD in the community and followed for 6 months. Participants were considered retained on MOUD through 6 months if they reported taking MOUD at every study interview without discontinuation. A high dose of MOUD was defined as a methadone dose > 85 mg or buprenorphine dose ≥ 16 mg. Multivariable logistic regression was conducted to assess factors associated with 6-month MOUD retention. Results: A total of 118 participants (73% male, 58% white, 36% with HIV) were included. Buprenorphine was initiated by 58% and 42% started methadone. MOUD retention was 49% and 58% among buprenorphine and methadone, respectively, at 6-months. In adjusted models, a high MOUD dose (OR = 4.71, 95% CI 2.05–10.84) and higher pain interference (OR = 1.59, 95% CI 1.15–2.19) was associated with MOUD retention. Conclusions: Adequate dosing of MOUD leads to improved retention on MOUD. Further, persons with high pain interference at baseline had higher odds of retention on MOUD. Both methadone and buprenorphine have analgesic effects, thus those with high pain interference could have dual benefits of MOUD for treating OUD and pain. Interventions should be tailored to improve adequate MOUD dosing to improve retention on MOUD.

Background: To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges. Methods: This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952).The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included. Discussion: The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost.

Reincarceration in prison or jail correlates with non-sustained HIV viral suppression, but HIV treatment outcomes in released prisoners who are reincarcerated have not recently been systematically assessed despite advances in antiretroviral treatment (ART) potency, simplicity, and tolerability.

IMPORTANCE Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined. OBJECTIVE To evaluate HIV treatment outcomes throughout incarceration, including jail and prison. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data on 882 prisoners within the Connecticut Department of Correction (2005-2012) with confirmed HIV infection, who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and CD4 lymphocyte measurements, and were prescribed antiretroviral therapy. MAIN OUTCOMES AND MEASURES Three electronic databases (correctional, laboratory, and pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, <400 copies/mL) on intake and release. Secondary outcomes were mean change in log-transformed HIV-1 RNA levels and mean change in CD4 lymphocyte count during incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt of directly observed therapy, and duration of incarceration were analyzed as possible explanatory variables for HIV viral suppression in logistic regression models. RESULTS Among 882 HIV-infected prisoners with 1185 incarceration periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count increased by 98 cells/µL over time, with a higher proportion achieving viral suppression by release compared with entry (70.0% vs 29.8%; P < .001); 36.9% of antiretroviral therapy (ART) regimens were changed during incarceration. After adjusting for baseline HIV-1 RNA level, prerelease viral suppression correlated with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26-2.59) and psychiatric disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI, 1.12-1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing strategy, or directly observed therapy. CONCLUSIONS AND RELEVANCE Though just one-third of HIV-infected prisoners receiving ART entered correctional facilities with viral suppression, HIV treatment was optimized during incarceration, resulting in the majority achieving viral suppression by release. Treatment for HIV within prison is facilitated by a highly structured environment and, when combined with simple well-tolerated ART regimens, can result in viral suppression during incarceration. In the absence of important and effective community-based resources, incarceration can be an opportunity of last resort to initiate continuous ART for individual health and, following the “treatment as prevention” paradigm, potentially reduce the likelihood of HIV transmission to others after release if continuity of HIV care is sustained.

The prevalence of HIV infection in correctional settings is several-fold higher than found in community settings. New approaches to identifying HIV infection among prisoners are urgently needed. In order to determine the HIV seroprevalence and to identify the correlates of HIV infection among female prisoners, an anonymous, but linked HIV serosurvey was conducted at Connecticut’s sole correctional facility for women (census=1,100). After removing all individual identifiers for inmates’ standardized clinical and risk behavior information, data are linked by a third source to blinded HIV-testing information by a third party. This three-step sequential process allows for anonymous HIV testing that can still be linked with deidentified clinical and behavioral data. Of the 3,315 subjects with complete information, 250 (7,5%) were HIV+. Of these, 157 (63%) selfreported being HIV+. Using multiple logistic regression analysis, having sex with a known HIV+ person [adjusted odds ratio (AOR)=9.1] and injection drug use (AOR=6.1) were the most highly correlated risk factors for HIV, whereas leukopenia (AOR=9.4) and hypoalbuminemia (AOR=7.2) were the most significant laboratory markers. Other independent correlates of HIV included self-report of syphilis (AOR=1.9) or genital herpes infection (AOR=2.7) and being Black (AOR=2.1) or Hispanic (AOR=2.2). The prevalence of HIV and HIV-risk behaviors is high among incarcerated women. Existing voluntary HIV counseling and testing programs do not completely target high-risk groups who remain part of the evolving epidemic. Defined demographic, behavioral, and clinical assessments may provide useful information for encouraging targeted counseling and testing. Newer targeted approaches merit further study to determine the effectiveness of this approach. Alternative methods of facilitating more widespread HIV testing, such as saliva tests, rapid serologic tests, and more routine testing in high HIV-prevalence areas should be considered both for clinical and for public health benefits.

The zebrafish lens opaque (lop) mutant was identified in a chemical mutagenesis screen. The lop mutant, which develops normally through 4 days postfertilization (dpf), exhibits several signs of lens and retinal degeneration at 7 dpf. Histology revealed disrupted lens fibers and increased numbers of nucleated cells within the mutant lens and anterior chamber. The mutant lens also exhibited aberrant epithelial cell morphologies and lacked a definitive transition zone, which suggests that secondary fiber differentiation was interrupted. In addition, the mutant exhibits severely reduced photoreceptors and a reduction in the number of horizontal cells at 7 dpf. Other retinal cell classes appeared unaffected in the mutant. Transmission electron microscopy and opsin immunohistochemistry showed that the different photoreceptor types were generated at the retinal margin, but the rods and cones failed to mature and disappeared. The mutant lens and retina also displayed increased cell proliferation based on proliferating cell nuclear antigen immunolabeling, suggesting that the lens opacity was due to unregulated cell proliferation and undifferentiated cell accumulation within the mutant lens. The lop mutant phenotype supports recent studies showing the lens has a role in regulating teleost retinal development. Developmental Dynamics 233:52–65, 2005. © 2005 Wiley‐Liss, Inc.

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%–20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%–20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.

Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV (PLH). Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To understand the role of MOUD – opioid agonist methadone, partial agonist buprenorphine and antagonist naltrexone – in HIV-1 persistence and reactivation, we will use molecular virology approaches to carry out the first prospective, longitudinal studies of adults living with HIV with OUD initiating MOUD. One of the major challenges to studying the impact of MOUD on HIV persistence is the low retention rate of study participants and the requirement of large-volume blood sampling to study the HIV proviral landscape and expression profiles.

Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV. Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To address the question of modulation of immune responses by MOUDs, we describe state of the art systems biology approaches to carry out the first prospective, longitudinal study of persons with and without HIV infection with OUD initiating MOUD.