A survey of barriers and facilitators to the adoption of buprenorphine prescribing after implementation of a New Jersey-wide incentivized DATA-2000 waiver training program.

BACKGROUND: Opioid-involved overdose deaths continue to rise in the US, despite availability of highly effective treatments for opioid use disorder (OUD), in part due to the insufficient number of treatment providers. Barriers include the need for providers to gain expertise and confidence in providing MOUD to their patients who need these treatments. To mitigate this barrier, New Jersey sponsored a buprenorphine training program with financial incentives for participation, which met the then existing requirement for the DATA-2000 waiver. In a 2019 follow-up survey, participants reported on barriers and facilitators to subsequent buprenorphine prescribing. METHODS: Participants in the training program completed a 10-min electronic survey distributed via email. The survey addressed demographics, practice characteristics, current buprenorphine prescribing, and barriers and facilitators to adoption and/or scale up of buprenorphine prescribing. RESULTS: Of the 440 attendees with a valid email address, 91 individuals completed the survey for a response rate of 20.6%. Of the 91 respondents, 89 were eligible prescribers and included in the final analysis. Respondents were predominantly female (n = 55, 59.6%) and physicians (n = 55, 61.8%); representing a broad range of specialties and practice sites. 65 (73%) of respondents completed the training and DEA-registration, but only 31 (34.8%) were actively prescribing buprenorphine. The most frequently cited barriers to buprenorphine prescribing were lack of access to support services such as specialists in addiction, behavioral health services, and psychiatry. The most frequently reported potential facilitators were integrated systems with direct access to addiction specialists and psychosocial services, easier referral to behavioral health services, more institutional support, and improved guidance on clinical practice standards for OUD treatment. CONCLUSION: More than half (52.3%) of those who completed incentivized training and DEA registration failed to actively prescribe buprenorphine. Results highlight provider perceptions of inadequate availability of support for the complex needs of patients with OUD and suggest that broader adoption of buprenorphine prescribing will require scaling up support to clinicians, including increased availability of specialized addiction and mental health services.

Racial/ethnic disparities in timely receipt of buprenorphine among Medicare disability beneficiaries.

BACKGROUND: Medicare disability beneficiaries (MDBs) have disproportionately high risk of opioid use disorder (OUD) and related harms given high rates of comorbidities and high-dose opioid prescribing. Despite this increased risk, little is known about timely receipt of medication for opioid use disorder (MOUD), including potential disparities by patient race/ethnicity or moderation by county-level characteristics. METHODS: National Medicare claims for a sample of MDBs with incident OUD diagnosis between March 2016 and June 2019 were linked with county-level data. Multivariable mixed effects Cox proportional hazards models estimated time (in days) to buprenorphine receipt within 180 days of incident OUD diagnosis. Primary exposures included individual-level race/ethnicity and county-level buprenorphine prescriber availability, percent non-Hispanic white (NHW) residents, and Social Deprivation Index (SDI) score. RESULTS: The sample (n=233,079) was predominantly White (72.3%), ≥45 years old (76.3%), and male (54.8%). Black (adjusted hazard ratio [aHR]=0.50; 95% CI, 0.47-0.54), Asian/Pacific Islander (aHR=0.54; 95% CI, 0.41-0.72), Hispanic/Latinx (aHR=0.81; 95% CI, 0.76-0.87), and Other racial/ethnic groups (aHR=0.75; 95% CI, 0.58-0.97) had a lower likelihood of timely buprenorphine than non-Hispanic white beneficiaries after adjusting for individual and county-level confounders. Timely buprenorphine receipt was positively associated with county-level buprenorphine prescriber availability (aHR=1.05; 95% CI, 1.04-1.07), percent non-Hispanic white residents (aHR=1.01; 95% CI, 1.00-1.01), and SDI (aHR=1.06; 95% CI, 1.01-1.10). CONCLUSIONS: Racial/ethnic disparities highlight the need to improve access to care for underserved groups. Implementing equity-focused quality and performance measures and developing interventions to increase office-based buprenorphine prescribing in predominantly minority race/ethnicity counties may reduce disparities in timely access to medication for OUD.

Overdose education and naloxone distribution program design informed by people who use drugs and naloxone distributors.

People who use drugs (PWUD) are the most directly affected by the overdose epidemic. However, they are not often targets of overdose education and naloxone distribution (OEND) programs. Instead, these programs target friends or family members of people prescribed opioids or general community members. This study aimed to understand the perspectives of PWUD and community naloxone distributors on OEND program design. We used a community-based participatory research model to elucidate participant perspectives on what OEND programs should look like in the context of each individual's specific risk environment. We conducted semi-structured in-depth interviews with PWUD and naloxone distributors (n = 30) in New Brunswick and Newark, New Jersey between February and November of 2022. We analyzed interviews using thematic analysis and identified the following themes: increasing naloxone knowledge, peer-based naloxone access, increasing PWUD-informed OEND program design, and desired broader OEND program scope. All Participants knew what naloxone was and emphasized that naloxone needed to be ubiquitous in the community. Participants prioritized peer-based distribution, integrating distribution into community organizations, and addressing psychosocial issues related to naloxone administration and drug use. In summary, PWUD and community naloxone distributors emphasized peer-led community naloxone distribution that prioritized novel ways for PWUD to access naloxone. OEND program design should prioritize PWUD's perspectives and direct community naloxone distribution.

HIV Prevention Research Experiences Among Men Who Have Sex With Men and Transgender Persons of Color.

PURPOSE: Black and Latinx MSM and transgender POC disproportionately experience new HIV diagnoses. Determining effective HIV prevention methods requires the inclusion of these communities in research and thorough post-trial experience evaluations. This study sought to evaluate the experiences of Black and Latinx MSM and transgender POC in HIV prevention research and identify facilitators and barriers to continued trials participation. METHODS: A survey was developed in partnership with the community engagement team based on emerging themes during research participant check-ins with the team. The survey was built in REDCap and distributed to participants via text message. The survey assessed experiences with the research process time commitments, study responsibilities, compensation, experiences with Truvada®, characteristics of the research study team and site, barriers to continued study participation, willingness to participate in future studies, and overall satisfaction. All statistical analysis was completed in Stata. RESULTS: Forty-four participants were enrolled in the study. Most participants (98%) were satisfied with their experiences in HIV prevention research. Job or school schedules were the most frequently cited barrier to study participation while Truvada® provision and adequate study visit compensation, length, number, and frequency were facilitators. Participants reported that research staff made them feel comfortable when talking about sexual behaviors, alcohol use, mental health, drug use, housing problems, violence in relationships, and legal problems. CONCLUSIONS: Evaluating the experiences of key communities in HIV prevention research can help identify barriers and facilitators to clinical trials engagement and improve the design of future trials.

The impact of COVID-19 on the treatment of opioid use disorder in carceral facilities: a cross-sectional study.

While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical.

Inclusion and diversity in clinical trials: Actionable steps to drive lasting change.

BACKGROUND: Improving diversity in clinical trials is essential in order to produce generalizable results. Although the importance of representation has become increasingly recognized, identifying strategies to approach this work remains elusive. This article reviews the proceedings of a multi-stakeholder conference about the current state of diversity in clinical trials and outlines actionable steps for improvement. METHODS: Conference attendees included representatives from the United States Food and Drug Administration (FDA), National Institutes of Health (NIH), practicing clinical investigators, pharmaceutical and device companies, community-based organizations, data analytics companies, and patient advocacy groups. At this virtual event, attendees were asked to consider key questions around best practices for engagement of underrepresented populations. RESULTS: Community engagement is an integral part of recruitment and retention of underrepresented groups. Decentralization of sites and use of digital tools can enhance the accessibility of clinical research. Finally, improving representation among investigators and clinical research staff may translate to diverse clinical trial participants. CONCLUSION: Improving diversity in clinical trials is an ethical and scientific imperative, which requires a multifaceted approach.

An atypical presentation of malaria in a 19-year-old woman.

We describe an atypical presentation of malaria in a 19-year-old female who emigrated from Nigeria to the United States one year prior to presentation. Her primary complaint was fever and occipital headache radiating down to the neck. Rapid antigen testing was positive for Plasmodium vivax/ovale and microscopy demonstrated the same. She received treatment with atovaquone-proguanil with improvement in symptoms but was lost to outpatient follow up. This case is unusual in several aspects: the 12-month latency in disease manifestation after her last epidemiologic exposure and the recovery of P. vivax/ovale which is uncommon in Nigeria. Appropriate identification of travel history, clinical presentation and disease epidemiology are necessary to guide pharmacologic treatment.

Satisfaction with group-based appointments among patients with opioid use disorder in an urban buprenorphine clinic.

Background: Successful implementation of group-based appointments can increase capacity to treat patients, reduce costs, and improve productivity. We sought to understand the acceptability of group-based appointments for opioid use disorder (OUD) in an urban clinical setting that treats predominantly ethnic minority populations. Methods: A survey collecting data on demographics, substance use, co-morbid psychiatric conditions, and satisfaction with group-based opioid treatment (GBOT) was conducted among patients 18 years and older with OUD attending an urban buprenorphine clinic between December 2019 and February 2020. Results: Thirty-nine patient surveys were completed. Among participants, 64.1% identified as Black/African American and 76.9% identified as male. The mean age was 51.2 years. Participants reported overall high levels of satisfaction with group-based appointments though GBOT was not strongly preferred over individual visits. On a 5-point Likert scale, 69.2% of participants agreed or strongly agreed that their medical needs were met during group-based appointments. A majority of participants agreed or strongly agreed that medical information received from the clinical team (97.4%) and other patients (82.1%) were valuable. Most participants (82.1%) reported adherence to treatment plans became easier since attending GBOT. Age and self-identified employment status as disabled or retired were positively associated with total satisfaction scores. Conclusions: Patients in a predominantly Black/African American and Hispanic/Latinx community with co-occurring mental health disorders and other substance use reported overall satisfaction with GBOT and would recommend this modality to other patients.

Perspectives of opioid use disorder treatment providers during COVID-19: Adapting to flexibilities and sustaining reforms.

OBJECTIVE: The COVID-19 pandemic led to unprecedented temporary federal and state regulatory flexibilities that rapidly transformed medication for opioid use disorder (MOUD) treatment delivery. This study aimed to understand changes in treatment providers' care during COVID-19, provider experiences with the adaptations, and perceptions of which changes should be sustained long-term. METHODS: We conducted in-depth, semi-structured interviews with 20 New Jersey MOUD providers, purposively sampled to reflect diversity in provider setting, specialty, and other characteristics. Using a rapid analysis approach, we summarized content within interview domains and analyzed domains across participants for recurring concepts and themes. RESULTS: MOUD treatment practice changes taking place during the COVID-19 pandemic included a rapid shift from in-person care to telehealth, reduction in frequency of toxicology testing and psychosocial/counseling services, and modifications to prescription durations and take-home methadone supplies. Modifications to practice were positively received and reinforced a sense of autonomy for providers as well as enhancing the ability to provide patient-centered care. All respondents expressed support for making temporary regulatory flexibilities permanent, but differed in their implementation of the flexibilities and the extent to which they planned to modify their own practices long-term. CONCLUSION: Findings support sustaining temporary regulatory and payment changes to MOUD practice, which may have improved treatment access and allowed for more flexible, individually tailored patient care. Few negative, unintended consequences were reported by providers, but more research is needed to evaluate the patient experience with changes to practice during the COVID-19 pandemic.

Comparisons of injection and non-injection opioid use among Black people in methadone treatment: A pilot in Detroit.

Rates of injection drug use (IDU) of opioids have been consistently lower among Black people relative to Non-Hispanic White people despite rising IDU estimates. While explanations have been proposed, no study has explored differences within a clinical sample of Black people in treatment who prefer IDU to non-IDU opioid administration. The purpose of this pilot study was to explore these differences guided by a seminal framework (e.g., market force, social network, and risk-taking characteristics), along with mental health symptoms, needle phobia, and injection perception variables. A purposive sample of 50 Black participants (58.0% male) were recruited from an opioid treatment program in Detroit by their preference for IDU (n = 16) versus non-IDU. The IDU group was younger, less educated, and younger at first treatment episode. They were more likely to report having been told they had bipolar disorder, PTSD, or anxiety, receiving mental health services as adults, and have a spouse/partner and close friends who injected opioids. The non-IDU group endorsed more symptoms of needle phobia. The non-IDU group also agreed more with statements that family and friends believe police mistreat people who inject drugs, and that people who inject opioids have a harder time quitting, are more likely to die from overdose, and have a harder time hiding it from family. These initial findings provide a rationale for a larger study with sex-specific analysis on factors associated with IDU among Black people to inform harm reduction efforts.

Long-acting buprenorphine vs. naltrexone opioid treatments in CJS-involved adults (EXIT-CJS).

The EXIT-CJS (N = 1005) multisite open-label randomized controlled trial will compare retention and effectiveness of extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) to treat opioid use disorder (OUD) among criminal justice system (CJS)-involved adults in six U.S. locales (New Jersey, New York City, Delaware, Oregon, Connecticut, and New Hampshire). With a pragmatic, noninferiority design, this study hypothesizes that XR-B (n = 335) will be noninferior to XR-NTX (n = 335) in retention-in-study-medication treatment (the primary outcome), self-reported opioid use, opioid-positive urine samples, opioid overdose events, and CJS recidivism. In addition, persons with OUD not eligible or interested in the RCT will be recruited into an enhanced treatment as usual arm (n = 335) to examine usual care outcomes in a quasi-experimental observational cohort.

No Significant Changes to Residual Viremia After Switch to Dolutegravir and Lamivudine in a Randomized Trial.

In the ASPIRE trial, antiretroviral therapy (ART) switch to dolutegravir plus lamivudine (DTG+3TC) was comparable to 3-drug ART in maintaining viral suppression by standard viral load assays. We used an ultrasensitive assay to assess whether this switch led to increased residual viremia. At entry, levels of residual viremia did not differ significantly between arms (DTG+3TC vs 3-drug ART: mean, 5.0 vs 4.2 HIV-1 RNA copies/mL; P = .64). After randomization, no significant between-group differences were found at either week 24 or 48. These results show no evidence for increased viral replication on DTG+3TC and support its further investigation as a dual ART strategy.

Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353.

BACKGROUND: The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable. OBJECTIVES: The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL. METHODS: Virological success was defined as HIV-1 RNA <50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA >200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (≤100 000 versus >100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684. RESULTS: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment. CONCLUSIONS: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA <500 000 copies/mL.

Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial.

Clinical Trials Registration: NCT02263326.

ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

Background: Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine. Methods: A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA <50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20 or >200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF. Results: One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the >100000 copies/mL and ≤100000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at ≥1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events. Conclusions: Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500000 copies/mL in this pilot trial, but a participant developed resistance mutations. Clinical Trials Registration: NCT02582684.

Long-Acting Antiretrovirals: Where Are We now?

PURPOSE OF REVIEW: Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. RECENT FINDINGS: Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

Determinants of HIV Phylogenetic Clustering in Chicago Among Young Black Men Who Have Sex With Men From the uConnect Cohort.

INTRODUCTION: Phylogenetic analysis determines similarities among HIV genetic sequences from persons infected with HIV, identifying clusters of transmission. We determined characteristics associated with both membership in an HIV transmission cluster and the number of clustered sequences among a cohort of young black men who have sex with men (YBMSM) in Chicago. METHODS: Pairwise genetic distances of HIV-1 pol sequences were collected during 2013-2016. Potential transmission ties were identified among HIV-infected persons whose sequences were ≤1.5% genetically distant. Putative transmission pairs were defined as ≥1 tie to another sequence. We then determined demographic and risk attributes associated with both membership in an HIV transmission cluster and the number of ties to the sequences from other persons in the cluster. RESULTS: Of 86 available sequences, 31 (36.0%) were tied to ≥1 other sequence. Through multivariable analyses, we determined that those who reported symptoms of depression and those who had a higher number of confidants in their network had significantly decreased odds of membership in transmission clusters. We found that those who had unstable housing and who reported heavy marijuana use had significantly more ties to other individuals within transmission clusters, whereas those identifying as bisexual, those participating in group sex, and those with higher numbers of sexual partners had significantly fewer ties. CONCLUSIONS: This study demonstrates the potential for combining phylogenetic and individual and network attributes to target HIV control efforts to persons with potentially higher transmission risk, as well as suggesting some unappreciated specific predictors of transmission risk among YBMSM in Chicago for future study.

Comparison of HIV Testing Uptake in an Urban Academic Emergency Department Using Different Testing Assays and Support Systems.

Despite 2006 recommendations by the Centers for Disease Control and Prevention for opt-out HIV testing in all healthcare settings, Emergency Department (ED) testing has been limited. We conducted an observational cohort study to assess the impact of two workflow interventions on the proportion of HIV tests ordered in an urban academic ED. First, a 4(th)-generation HIV antigen/antibody combination test replaced the existing assay, and ED staff continued to notify patients of their reactive tests. Six months later, the HIV Rapid Diagnosis Team, composed of an Infectious Diseases (ID) physician and the HIV Advanced Practice Nurse, immediately assisted with disclosure of positive results to the patients and facilitated linkage to outpatient care. The new assay did not change the proportion of HIV tests ordered (0.14-0.11%, χ2, p = 0.2). However, ID support was associated with a statistically significant increase in the proportion of HIV tests ordered (0.14-0.43%, χ2, p < 0.00010) and a nonstatistically significant increase in the proportion of new HIV diagnoses (1.6-6.8%, Fisher exact test = 0.113). Male gender and lack of insurance were associated with a reactive HIV test. Reduction of barriers to linkage to outpatient HIV care through a collaborative relationship between the ED and ID team increased HIV testing and diagnosis. The role of this model as a component of a universal HIV screening program will need to be further assessed.