Xylazine co-occurrence with illicit fentanyl is a growing threat in the Deep South: a retrospective study of decedent data.

BACKGROUND: Xylazine is a dangerous veterinary sedative found mainly in illicit fentanyl in the Northeast and Midwest. Its role in the Deep South overdose crisis is not well-characterized. METHODS: We conducted a retrospective review of autopsy data in Jefferson County, Alabama to identify trends in xylazine prevalence among people who fatally overdosed from June 2019 through June 2023. RESULTS: 165 decedents met inclusion criteria. While the first identified xylazine-associated overdose was in June 2019, xylazine has become consistently prevalent since January 2021. All cases of xylazine-associated fatal overdoses were accompanied by fentanyl, and most (75.4%) involved poly-drug stimulant use. The average age was 42.2, and most decedents were white (58.8%) and male (68.5%). Overall, 18.2% of people were unhoused at the time of death. DISCUSSION: Xylazine is prevalent in the Deep South. Efforts to promote harm reduction, publicly viewable drug supply trends, and legalization of drug checking and syringe service programs should be prioritized.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel.

Importance: Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice. Objective: Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection. Evidence Review: A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered. Findings: Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential. Conclusions and Relevance: Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

Human Immunodeficiency Virus/Sexually Transmitted Infection Testing Preferences for Young Black Men Who Have Sex With Men in the Southeastern United States: Implications for a Post-COVID-19 Era.

BACKGROUND: Little is known regarding human immunodeficiency virus (HIV)/sexually transmitted infection (STI) testing preferences for location, staffing, and hours of operation among Young Black men who have sex with men (YBMSM) in the Southeastern United States, a population at high risk for HIV/STIs. We used a discrete choice experiment to explore these preferences. METHODS: Young Black men who have sex with men ages 16 to 35 years in Birmingham, AL and Jackson, MS completed online surveys evaluating their preferences (best/worst) for HIV/STI testing locations, staffing, hours, method of results notification, and cost. They also selected preferred combinations of these variables through choice tasks. Results were analyzed using joint best/worst and discrete choice experiment models. RESULTS: Between June 2018 and December 2019, participants in Alabama (n = 54) and Mississippi (n = 159) completed online surveys. Both groups preferred stationary testing locations over mobile testing vans, with the most significant difference favoring STI testing-only clinics in Mississippi and local health departments in Alabama (P < 0.001). Technician-performed tests or self-testing were significantly less preferred compared with clinician-performed testing for both groups (P < 0.0001 and P < 0.0001, respectively). Free testing and phone results notification (versus text) were preferred by both groups. The most desirable combination among all participants was weekday clinician-performed testing at the health department for $5. CONCLUSIONS: Young Black men who have sex with men in the Southeastern United States prefer traditional testing locations staffed by experienced personnel. Combination choices are influenced by services that are low or no cost. More research is needed to inform the best way(s) to provide affordable, high-quality HIV/STI testing services for YBMSM, particularly in the post-COVID-19 era when sexual health care delivery models are evolving toward home-based and remote health-focused strategies.

Expanding access to substance use services and mental health care for people with HIV in Alabama, a technology readiness assessment using a mixed methods approach.

BACKGROUND: Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a large rural burden of disease. Mental health (MH) and substance use disorders (SUD) represent obstacles to HIV care in rural areas lacking Medicaid expansion and infrastructure. Evidence-informed technologies, such as telehealth, may enhance SUD and MH services but remain understudied in rural regions. METHODS: We conducted a readiness assessment using a mixed methods approach to explore opportunities for enhanced SUD and MH screening using electronic patient reported outcomes (ePROs) and telehealth at five Ryan White HIV/AIDS Program-funded clinics in AL. Clinic providers and staff from each site (N = 16) completed the Organizational Readiness to Implement Change (ORIC) assessment and interviews regarding existing services and readiness to change. People with HIV from each site (PLH, N = 18) completed surveys on the acceptability and accessibility of technology for healthcare. RESULTS: Surveys and interviews revealed that all clinics screen for depression annually by use of the Patient Health Questionnaire-9 (PHQ9). SUD screening is less frequent and unstandardized. Telehealth is available at all sites, with three of the five sites beginning services due to the COVID-19 pandemic; however, telehealth for MH and SUD services is not standardized across sites. Results demonstrate an overall readiness to adopt standardized screenings and expand telehealth services beyond HIV services at clinics. There were several concerns including Wi-Fi access, staff capacity, and patients' technological literacy. A sample of 18 people with HIV (PWH), ages 18 to 65 years, participated in surveys; all demonstrated adequate technology literacy. A majority had accessed telehealth and were not concerned about it being too complicated or limiting communication. There were some concerns around lack of in-person interaction and lack of a physical exam and high-quality care with telehealth. CONCLUSION: This study of PWH and the clinics that serve them reveals opportunities to expand SUD and MH services in rural regions using technology. Areas for improvement include implementing routine SUD screening, expanding telehealth while maintaining opportunities for in-person interaction, and using standardized ePROs that are completed by patients, in order to minimize stigma and bias.

Transportability From Randomized Trials to Clinical Care: On Initial HIV Treatment With Efavirenz and Suicidal Thoughts or Behaviors.

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001-2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: -0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.

An Integrated Hospital Protocol for Persons With Injection-Related Infections May Increase Medications for Opioid Use Disorder Use but Challenges Remain.

BACKGROUND: Hospital-based strategies that link persons with infectious complications of opioid use disorder (OUD) to medications for OUD (MOUD) are of great interest. The objective of this study is to determine whether a hospital-based protocol would increase the use of MOUD and to identify barriers to MOUD during admission and at the time of discharge. METHODS: This study included participants with a documented or suspected history of injection drug usage receiving care for an infection at the University of Alabama at Birmingham Hospital from 2015 to 2018. The protocol, the intravenous antibiotic and addiction team (IVAT), included Addiction Medicine and Infectious Diseases consultation and a 9-item risk assessment. We quantified MOUD use before and after IVAT and used logistic regression to determine factors associated with MOUD. We explored barriers to MOUD uptake using chart review. RESULTS: A total of 37 and 98 patients met criteria in the pre- and post-IVAT periods, respectively. With IVAT, the percentage with OUD receiving MOUD significantly increased (29% pre-IVAT and 37% post-IVAT; P = .026) and MOUD use was higher in "high risk" participants (62%). Clinical and sociodemographic factors were not associated with MOUD receipt. CONCLUSIONS: A hospital-based protocol may increase the use of MOUD; however, the uptake of MOUD remains suboptimal (<50%).

Quantitative evaluation on the challenges and opportunities in the recruitment of young Black men who have sex with men for sexual health research in the southern US.

Background Young Black men who have sex with men (YBMSM) in the Deep South are at increased risk of sexually transmissible infections (STIs) and HIV. The present two-phase study evaluated the recruitment of YBMSM, both HIV infected and uninfected, for a sexual health study in Birmingham (AL, USA) from 2017 to 2019 and explored alternative patient-centred recruitment methods. METHODS: In Phase 1, YBMSM were recruited to participate in focus groups related to STI testing. To recruit participants, flyers were displayed in businesses, clinics and lesbian, gay, bisexual and transgender (LGBT)-friendly organisations. In addition, research staff at an HIV clinic referred participants and a recruiter attended community events. In Phase 2, YB men were asked, in an electronic survey, 'What is the best way to recruit young, Black men for surveys about sexual health?' and 'If you selected 'social media', which social media sites or 'apps' do you think are best to recruit young, Black men?'. RESULTS: In Phase 1, 38 YBMSM participated in focus groups. Twelve (32%) were recruited by referral, 9 (24%) were recruited from an HIV clinic and 11 (29%) were recruited from an LGBT organisation. The recruiter was unable to recruit any participants. In Phase 2, 55 YBMSM completed the electronic survey. Twenty-six (48%) selected social media as the best way to recruit young Black men for surveys about sexual health, and their suggested platforms included Instagram, Facebook, Twitter, Snapchat, Kik and dating apps. Seventeen (31%) selected 'Having young gay black men recruit from their friends and acquaintances' as the ideal recruitment strategy. CONCLUSION: Challenges persist when recruiting YBMSM for sexual health research. Social media may provide better access to this vulnerable population.

A 9-Point Risk Assessment for Patients Who Inject Drugs and Require Intravenous Antibiotics: Focusing Inpatient Resources on Patients at Greatest Risk of Ongoing Drug Use.

A 9-point risk assessment identified persons with a history of injection drug use who were safe for discharge. "Low-risk" patients were discharged with outpatient antibiotics; others continued inpatient treatment. Use of the assessment reduced the mean length of stay by 20 days and total direct cost by 33%, creating capacity for an additional 333 patients.

Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug.

PURPOSE OF REVIEW: The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations. Although TDF is well tolerated, the potential for kidney and bone toxicity has important implications for public health given the large number of individuals exposed to TDF worldwide. This review summarizes the recent literature on kidney and bone health in individuals treated with TDF and the newer prodrug tenofovir alafenamide (TAF). RECENT FINDINGS: Risk factors for TDF toxicity appear to be similar in patients treated for HIV or hepatitis B virus and in HIV-uninfected PrEP users, although drug-drug interactions are a more important concern in HIV-positive individuals. The risk of toxicity appears to be lower with TAF, but further studies are needed to confirm the safety of long-term use and to evaluate the efficacy of TAF-based PrEP. SUMMARY: Nephrologists should be aware of the potential kidney and bone toxicity of TDF, as well as unique situations in which the newer prodrug TAF may contribute to kidney injury.

Mental health service utilization is associated with retention in care among persons living with HIV at a university-affiliated HIV clinic.

BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons living with HIV (PLWH) and are associated with poor health outcomes. Optimizing retention in primary care is vital, as poor retention is associated with delayed receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health outcomes, including failure to suppress viral load, decreased CD4 counts, and clinically significant ARV drug resistance. We hypothesized that MH service utilization would be associated with improved retention in care for patients with HIV and MH comorbidities. METHODS: This is a retrospective analysis of PLWH initiating outpatient HIV health care at a university-affiliated HIV clinic between January 2007 and December 2013. We examined the association between MH service utilization and retention in care, the outcome of interest, using univariate and multivariable logistic regression. RESULTS: Overall, 627 (84.4%) out of 743 patients were retained in care using the Health Resources & Services Administration HIV/AIDS Bureau (HRSA/HAB) metric. A multivariable model adjusted for several sociodemographic factors, MH comorbidities, and MH service utilization. The results suggest that lack of health insurance (public ORadj = 0.3, p < 0.01; no insurance ORadj = 0.4, p < 0.01) and ≥ 3 MH comorbidities (ORadj = 0.3, P = 0.01) were associated with decreased retention in care. Conversely, older age (> 45 years, ORadj. = 1.6, p = 0.14) and ≥ 3 MH service utilization visits (ORadj. = 6.8, p < 0.01) were associated with increased retention in care. CONCLUSIONS: Even in the absence of documented MH comorbidities, improved retention in care was observed with increasing MH service utilization. In order to achieve the US-based National HIV/AIDS Strategy goal of 90% retention in care for PLWH, MH service utilization should be considered along with other evidence-based interventions to improve retention for PLWH newly engaged in care.

Antiretroviral Therapy Initiation and Changes in Self-Reported Depression.

In this retrospective study of treatment-naive PLWH initiating antiretroviral therapy, the score for the depression scale of the Patient Health Questionnaire (PHQ-9) was significantly higher at baseline (median, 6.0; interquartile range, 2-11) than at 12 months (3.0; 0-8; P < .001). Baseline depression and lack of insurance are associated with 12-month depression, but receipt of efavirenz-based antiretroviral therapy is not.

Immunization costs and programmatic barriers at an urban HIV clinic.

BACKGROUND: Although the increasing number of recommended immunizations is essential for patients infected with human immunodeficiency virus (HIV), the potentially uncompensated costs of expanded immunizations will present significant challenges for clinics and health systems serving HIV-infected patients. METHODS: We estimated costs of providing Gardasil, Prevnar, and Zostavax to eligible patients at a US Ryan White Part C academically affiliated HIV clinic in 2013. Clinic expenditures were calculated using vaccine price and administrative fees. Revenue was calculated using insurance reimbursement data for vaccination and administration. Three scenarios were used: 100% uptake of vaccines, adjusted uptake based on published rates, and adjusted reimbursement according to pre-Affordable Care Act (ACA) insurance status. RESULTS: 2887 patients (27% Medicare, 13% Alabama Medicaid, 26% Commercial, 34% Uninsured), received care with wide variation in immunization reimbursement ($0 to $210) by insurance and vaccine. The net yield (revenue minus expenditure) was calculated for each vaccine. Prevnar was most costly: annual net yield of -$60 691. Provision of all 3 vaccines would lead to a net yield of -$97 122. Adjusting for reduced uptake led to annual clinic losses of $44 119. Using pre-ACA reimbursement for immunization of the uninsured led to reduced clinic losses (-$62 326), attributable to reimbursement via Ryan White funds. CONCLUSIONS: A cost analysis of 3 vaccines shows great variation in insurance coverage, with potential losses of almost $100 000 for one HIV clinic if eligible patients received vaccinations in one calendar year. Adequate, cost neutral reimbursement should be instituted if medical providers and health systems are to achieve Advisory Committee on Immunization Practices immunization recommendations for both HIV positive and negative adults.

Injection Drug Use Alters Plasma Regulation of the B Cell Response.

The opioid epidemic continues to be a major public health issue that includes millions of people who inject drugs (PWID). PWID have increased incidence of serious infections, including HIV as well as metabolic and inflammatory sequelae. We sought to discern the extent of systemic alterations in humoral immunity associated with injection drug use, including alterations in the plasma proteome and its regulation of B cell responsiveness. Comprehensive plasma proteomics analysis of HIV negative/hepatitis C negative individuals with a history of recent injection heroin use was performed using mass spectrometry and ELISA. The effects of plasma from PWID and healthy controls on the in vitro proliferation and transcriptional profile of B cell responses to stimulation were determined by flow cytometry and RNA-Seq. The plasma proteome of PWID was distinct from healthy control individuals, with numerous immune-related analytes significantly altered in PWID, including complement (C3, C5, C9), immunoglobulin (IgD, IgM, kappa light chain), and other inflammatory mediators (CXCL4, LPS binding protein, C-reactive protein). The plasma of PWID suppressed the in vitro proliferation of B cells. Transcriptome analysis indicated that PWID plasma treatment increased B cell receptor and CD40 signaling and shifted B cell differentiation from plasma cell-like toward germinal center B cell-like transcriptional profiles. These results indicate that the systemic inflammatory milieu is substantially altered in PWID and may impact their B cell responses.

Strategies to Improve Patient-Centered Care for Drug Use-Associated Infective Endocarditis: JACC Focus Seminar 2/4.

Drug use-associated infective endocarditis (DUA-IE) is a major cause of illness and death for people with substance use disorder (SUD). Investigations to date have largely focused on advancing the care of patients with DUA-IE and included drug use disorder treatment, decisions about surgery, and choice of antibiotics during the period of hospitalization. Transitions from hospital to outpatient care are relatively unstudied and frequently a key factor of uncontrolled infection, continued substance use, and death. In this paper, we review the evidence supporting cross-disciplinary care for people with DUA-IE and highlight domains that need further clinician, institutional, and research investment in clinicians and institutions. We highlight best practices for treating people with DUA-IE, with a focus on addressing health disparities, meeting health-related social needs, and policy changes that can support care for people with DUA-IE in the hospital and when transitioning to the community.

Hospitalization is a missed opportunity for HIV screening, pre-exposure prophylaxis, and treatment.

BACKGROUND: Hospitalization is a "reachable moment" for people who inject drugs (PWID), but preventive care including HIV testing, prevention and treatment is rarely offered within inpatient settings. METHODS: We conducted a multisite, retrospective cohort study of patients with opioid use disorder with infectious complications of injection drug use hospitalized between 1/1/2018-12/31/2018. We evaluated HIV care continuum outcomes using descriptive statistics and hypothesis tests for intergroup differences. RESULTS: 322 patients were included. Of 300 patients without known HIV, only 2 had a documented discussion of PrEP, while only 1 was prescribed PrEP on discharge. Among the 22 people with HIV (PWH), only 13 (59%) had a viral load collected during admission of whom all were viremic and 10 (45%) were successfully linked to care post-discharge. Rates of readmission, Medicaid or uninsured status, and unstable housing were high in both groups. DISCUSSION: We observed poor provision of HIV testing, PrEP and other HIV services for hospitalized PWID across multiple U.S. medical centers. Future initiatives should focus on providing this group with comprehensive HIV testing and treatment services through a status neutral approach.

Perspectives on benefits and risks of creation of an "injection drug use" billing code.

People with substance use disorder (SUD) face barriers to prevention and treatment services, increasing risk for hospitalization and death. Injection drug use (IDU) can lead to an increased risk of overdose and infections. However, identifying people who inject drugs (PWID) within healthcare systems is challenging. International Classification of Disease (ICD-10) codes are used for billing and tracking healthcare utilization. In this commentary, experts in the field weigh the benefits and risks of creating an IDU-specific ICD-10 code. Potential benefits include earlier identification, better access to health services, and improved systems of resource allocation. Potential risks include further stigmatization of PWID and, if not tied to financial reimbursement, low rates of code utilization. As the current systems of identifying PWID are lacking, we feel that a guided operationalization of an ICD code to identify PWID could improve quantitative and epidemiological research accuracy and, therefore, support the health and well-being of PWID.

Multi-task transfer learning for the prediction of entity modifiers in clinical text: application to opioid use disorder case detection.

BACKGROUND: The semantics of entities extracted from a clinical text can be dramatically altered by modifiers, including entity negation, uncertainty, conditionality, severity, and subject. Existing models for determining modifiers of clinical entities involve regular expression or features weights that are trained independently for each modifier. METHODS: We develop and evaluate a multi-task transformer architecture design where modifiers are learned and predicted jointly using the publicly available SemEval 2015 Task 14 corpus and a new Opioid Use Disorder (OUD) data set that contains modifiers shared with SemEval as well as novel modifiers specific for OUD. We evaluate the effectiveness of our multi-task learning approach versus previously published systems and assess the feasibility of transfer learning for clinical entity modifiers when only a portion of clinical modifiers are shared. RESULTS: Our approach achieved state-of-the-art results on the ShARe corpus from SemEval 2015 Task 14, showing an increase of 1.1% on weighted accuracy, 1.7% on unweighted accuracy, and 10% on micro F1 scores. CONCLUSIONS: We show that learned weights from our shared model can be effectively transferred to a new partially matched data set, validating the use of transfer learning for clinical text modifiers.