Drug Decriminalization, Fentanyl, and Fatal Overdoses in Oregon.

Importance: With the implementation of Measure 110 (M110) in 2021, Oregon became the first US state to decriminalize small amounts of any drug for personal use. To date, no analysis of the association of this law with overdose mortality has fully accounted for the introduction of fentanyl-a substance that is known to drive fatal overdose-to Oregon's unregulated drug market. Objective: To evaluate whether the decriminalization of drug possession in Oregon was associated with changes in fatal drug overdose rates after accounting for the rapid spread of fentanyl in Oregon's unregulated drug market. Design, Setting, and Participants: In this cohort study, the association between fatal overdose and enactment of M110 was analyzed using a matrix completion synthetic control method. The control group consisted of the 48 US states and Washington, DC, all of which did not decriminalize drugs. The rapid spread of fentanyl in unregulated drug markets was determined using the state-level percentage of all samples reported to the National Forensic Laboratory Information System that were identified as fentanyl or its analogues. Mortality data were obtained from the Centers for Disease Control and Prevention for January 1, 2008, to December 31, 2022. Data analysis was performed from fall 2023 through spring 2024. Exposures: Measure 110 took effect in Oregon on February 1, 2021. Main Outcomes and Measures: The primary outcome assessed was fatal drug overdose rates per half-year. A changepoint analysis also determined when each state experienced a rapid escalation of fentanyl in its unregulated drug market. Results: In this analysis, rapid spread of fentanyl in Oregon's unregulated drug supply occurred in the first half of 2021, contemporaneous with enactment of M110. A positive crude association was found between drug decriminalization and fatal overdose rate per 100 000 per half year (estimate [SE], 1.83 [0.47]; P < .001). After adjusting for the spread of fentanyl as a confounder, the effect size changed signs (estimate [SE], -0.51 [0.61]; P = .41) and there was no longer an association between decriminalization and overdose mortality in Oregon. Sensitivity analyses were consistent with this result. Conclusions and Relevance: In this cohort study of fatal drug overdose and the spread of fentanyl through Oregon's unregulated drug market, no association between M110 and fatal overdose rates was observed. Future evaluations of the health effects of drug policies should account for changes in the composition of unregulated drug markets.

Housing and Displacement as Risk Factors for Negative Health Outcomes Among People Who Inject Drugs in Los Angeles, CA, and Denver, CO, USA.

Background The United States is currently experiencing a housing and homelessness crisis. In response, many cities have adopted policies of displacement that move unhoused people from place to place. Recent research indicates that these policies may have negative health impacts on unhoused people who use drugs. We sought to examine health risks associated with government-enforced displacement among unhoused people who inject drugs (PWID). Methods We interviewed a community-recruited sample of opioid-using PWID in Los Angeles, CA and Denver, CO between April 2021 and November 2022 (N = 472) about their demographic/socioeconomic characteristics, drug use patterns, housing status, government-enforced displacement including items discarded during displacements, and health risks. We constructed binomial generalized linear regression to examine the risk ratio of non-fatal overdose, and syringe and cooker/cotton sharing between four groups of participants: housed, unhoused and not displaced, unhoused and relocated voluntarily, and unhoused and displaced in the last three months. Results In the last 3 months, 52% of participants were unhoused and displaced by the government. Among those who were displaced, median number of government-enforced displacements was 3 with 69% reporting loss of syringes, 56% loss of naloxone, and 22% loss of buprenorphine medicine. In multivariate models, risk ratios for unhoused and displaced participants were higher for nonfatal overdose and cooker/cotton sharing as compared to housed participants. Risk ratios for syringe sharing amongst unhoused participants did not differ significantly. Conclusions Unhoused and displaced PWID experience elevated health risks. Ending the use of government-enforced displacement of unhoused PWID is essential to reducing health risk in this population.

Racialized environments and syringe services program implementation: County-level factors.

OBJECTIVE: Racialized health inequities in substance use-related harms might emerge from differential access to syringe service programs (SSPs). To explore this, we examined the association between county-level racialized environments, other factors, and (1) SSP presence, and (2) per capita syringe and (3) naloxone distribution. METHODS: 2021 US National Survey of SSP data (n=295/412;72 % response rate) was used to identify SSP presence and the sum of syringes and naloxone doses distributed in 2020 by county. Study measures included racial residential segregation (RRS; i.e., divergence and dissimilarity indexes for Black:Non-Hispanic White & Hispanic:Non-Hispanic White) and covariates (i.e., demographic proportions, urban/suburban/rural classifications, 2020 US presidential Republican vote share, and overdose mortality from 2019). We used logit Generalized Estimating Equations to determine factors associated with county-level SSP presence, and zero inflated negative binomial regression models to determine factors associated with per capita syringe and naloxone distribution. RESULTS: SSPs were reported in 9 % (283/3106) of US counties. SSP presence was associated with higher divergence and dissimilarity indexes, urban and suburban counties, higher opioid overdose mortality, and lower 2020 Republican presidential vote share. Per capita syringes distributed was associated with lower RRS (divergence and Hispanic:White dissimilarity), lower racially minoritized population proportions and rural counties, while per capita naloxone distribution was associated with lower Hispanic and "other" population proportions, and rural counties. CONCLUSIONS: Racialized environments are associated with SSP presence but not the scope of those programs. Preventing HIV and HCV outbreaks, and overdose deaths requires addressing community level factors that influence SSP implementation and accessibility.

Financial barriers, facilitators, and strategies among syringe services programs in the U.S., and their impact on implementation and health outcomes.

Syringe Services Programs (SSPs) provide evidence-based services like drug use equipment to prevent infectious disease, overdose prevention education, and naloxone distribution to people who use drugs (PWUD). However, inadequate funding threatens provision of these interventions. This study aimed to document how the current funding landscape impacted determinants of SSP implementation, particularly describing financial and staffing barriers, facilitators, and proposed strategies, using qualitative methods informed by three implementation research frameworks. We interviewed 20 leaders of SSPs in the United States using a semi-structured interview guide. Participants described how structural stigma against PWUD led to insufficient and restrictive funding, and burdensome reporting for SSPs. This resulted in harming program implementation outcomes like reach, fidelity, and sustainability. Inadequate funding also led to insufficient staffing and subsequent staff stress, burnout, and turnover. Taken together, these barriers threatened the implementation of evidence-based interventions that SSPs provided, ultimately harming their ability to effectively address health outcomes like infectious disease transmission and opioid overdose mortality within their communities. Interviewees described how upstream policy strategies like political advocacy might address structural stigma at the federal level. Participants also highlighted state-level efforts like harm reduction-centered funding, technical assistance and capacity-building, and clearinghouse programs that may facilitate better implementation and health outcomes. A more robust understanding of the relationship between financial barriers, facilitators, and strategies on implementation and health outcomes represents a novel and vital area of research within harm reduction literature.

"If everyone knew about this, how many lives could we save?": Do drug suppliers have a role in reducing overdose risk?

Introduction: An unpredictable illicit drug supply is driving high levels of overdose death in North America. Prior research has demonstrated the importance of involving people who use drugs in harm reduction intervention design and implementation. The inclusion of people who supply drugs in these efforts has been scant. We explore this possibility by interviewing persons targeted by a harm reduction educational program designed specifically for people who supply drugs. Methods: In-person interviews with people who use drugs were conducted in 2022 in Indianapolis, Indiana. We conducted a thematic analysis of data from six interviews with people who were either primarily or secondarily trained through this harm reduction training for people who supply drugs. Results: Participants described a diverse array of harm reduction strategies, some gained through the targeted education program, which they regularly practiced as they consumed and/or supplied drugs to others. People who supply drugs were regularly identified as key actors capable of widely reducing risk across drug networks. Participants described being motivated by a moral imperative to protect community members, tying the previous loss of friends and loved ones to overdose to their commitments to the safety of others. Conclusion: This article contributes to the scholarship on the role of people who supply drugs in implementing harm reduction interventions and reducing overdose risk. Better enabling grassroots harm reduction organizations to provide people who supply drugs with harm reduction training and access to harm reduction resources may help to reduce drug-related harms.

Comparing harm reduction and overdose response services between community-based and public health department syringe service programmes using a national cross-sectional survey.

Background: Syringe services programmes (SSPs) are an evidence-based strategy to reduce infectious diseases and deliver overdose prevention interventions for people who use drugs. They face regulatory, administrative, and funding barriers that limit their implementation in the US, though the federal government recently began providing funding to support these efforts. In this study we aim to understand whether the organisational characteristics of SSPs are associated with the provision of syringe and other overdose response strategies. Methods: We examine four outcomes using the National Survey of Syringe Services Programs (NSSSP) (N = 472): syringe distribution, naloxone distribution, fentanyl test strip (FTS) availability, and buprenorphine implementation. These outcomes are assessed across three organizational categories of SSPs-those operated by public health departments (DPH), community-based organizations (CBOs) with government funding, and CBOs without government funding-while adjusting for community-level confounders. Findings: The proportion of SSPs by organizational category was 36% DPH, 42% CBOs with government funding, and 22% CBOs without government funding. Adjusting for community-level differences, we found that CBO SSPs with government funding had significantly higher provision of all four syringe and overdose response services as compared to DPH SSPs and across three of the four services as compared to CBO SSPs without government funding. CBO SSPs without government funding still had significantly higher provision of three of the four services as compared to programmes maintained by the DPH. Interpretation: CBO SSPs have strong potential to expand overdose response services nationally, particularly if provided with sustained and adequate funding. Communities should aim to provide funding that does not hinder SSP innovation so they can remain flexible in responding to local needs. Funding: This study was supported by Arnold Ventures (20-05172).

Funding and Delivery of Syringe Services Programs in the United States, 2022.

Objectives. To describe the current financial health of syringe services programs (SSPs) in the United States and to assess the predictors of SSP budget levels and associations with delivery of public health interventions. Methods. We surveyed all known SSPs operating in the United States from February to June 2022 (n = 456), of which 68% responded (n = 311). We used general estimating equations to assess factors influencing SSP budget size and estimated the effects of budget size on multiple measures of SSP services. Results. The median SSP annual budget was $100 000 (interquartile range = $20 159‒$290 000). SSPs operating in urban counties and counties with higher levels of opioid overdose mortality had significantly higher budget levels, while SSPs located in counties with higher levels of Republican voting in 2020 had significantly lower budget levels. SSP budget levels were significantly and positively associated with syringe and naloxone distribution coverage. Conclusions. Current SSP funding levels do not meet minimum benchmarks. Increased funding would help SSPs meet community health needs. Public Health Implications. Federal, state, and local initiatives should prioritize sustained SSP funding to optimize their potential in addressing multiple public health crises. (Am J Public Health. 2024;114(4):435-443. https://doi.org/10.2105/AJPH.2024.307583).

Radical hospitality: Innovative programming to build community and meet the needs of people who use drugs at a government-sanctioned overdose prevention site in San Francisco, California.

BACKGROUND: The Tenderloin Center (TLC), a multi-service center where people could receive or be connected to basic needs, behavioral health care, housing, and medical services, was open in San Francisco for 46 weeks in 2022. Within a week of operation, services expanded to include an overdose prevention site (OPS), also known as safe consumption site. OPSs have operated internationally for over three decades, but government-sanctioned OPSs have only recently been implemented in the United States. We used ethnographic methods to understand the ways in which a sanctioned OPS, situated in a multi-service center, impacts the lives of people who use drugs (PWUD). METHODS: We conducted participant observation and in-depth interviews June-December 2022. Extensive field notes and 39 in-depth interviews with 24 TLC guests and 15 TLC staff were analyzed using an inductive analysis approach. Interviewees were asked detailed questions about their experiences using and working at the TLC. RESULTS: TLC guests and staff described an atmosphere where radical hospitality-welcoming guests with extraordinary warmth, generosity, and unconditional acceptance-was central to the culture. We found that the co-location of an OPS within a multi-service agency (1) allowed for the culture of radical hospitality to flourish, (2) yielded a convenient one-stop shop model, (3) created a space for community building, and (4) offered safety and respite to guests. CONCLUSIONS: The co-location of an OPS within a multi-service drop-in center is an important example of how such an organization can build positive sociality among PWUD while protecting autonomy and reducing overdose mortality. Overdose response and reversal is an act of relational accountability in which friends, peers, and even strangers intervene to protect and revive one another. This powerful intervention was operationalized as an anti-oppressive, horizontal activity through radical hospitality with a built environment that allowed PWUD to be both social and safe.

Organize and mobilize for implementation effectiveness to improve overdose education and naloxone distribution from syringe services programs: a randomized controlled trial.

BACKGROUND: The United States (US) continues to face decades-long increases in opioid overdose fatalities. As an opioid overdose reversal medication, naloxone can dramatically reduce opioid overdose mortality rates when distributed to people likely to experience or witness an opioid overdose and packaged with education on its use, known as overdose education and naloxone distribution (OEND). Syringe services programs (SSPs) are ideal venues for OEND with staff who are culturally competent in providing services for people who are at risk of experiencing or observing an opioid overdose. We carried out a randomized controlled trial of SSPs to understand the effectiveness of the organize and mobilize for implementation effectiveness (OMIE) approach at improving OEND implementation effectiveness within SSPs. METHODS: Using simple randomization, 105 SSPs were enrolled into the trial and assigned to one of two study arms - (1) dissemination of OEND best practice recommendations (Control SSPs) or the OMIE approach along with dissemination of the OEND best practice recommendations (i.e., OMIE SSPs). OMIE SSPs could participate in 60-min OMIE sessions once a month for up to 12 months. At 12-month post-baseline, 102 of 105 SSPs (97%) responded to the follow-up survey. RESULTS: The median number of sessions completed by OMIE SSPs was 10. Comparing OMIE SSPs to control SSPs, we observed significant increases in the number of participants receiving naloxone (incidence rate ratio: 2.15; 95% CI: 1.42, 3.25; p < 0.01) and the rate of naloxone doses distributed per SSP participant (adjusted incidence rate ratio: 1.97; 95% CI: 1.18, 3.30; p = 0.01). We observed no statistically significant difference in the number of adopted best practices between conditions (difference in means 0.2, 95% CI: - 0.7, 1.0; p = 0.68). We also observed a threshold effect where SSPs receiving a higher OMIE dose had greater effect sizes with regard to the number of people given naloxone and the number of naloxone doses distributed. CONCLUSIONS: In conclusion, the multifaceted OMIE approach was effective at increasing naloxone distribution from SSPs, despite substantial external shocks during the trial. These findings have major implications for addressing the overdose crisis, which has continued unabated for decades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03924505 . Registered 19 April 2019.

Characterizing Opioid Withdrawal Experiences and Consequences Among a Community Sample of People Who Use Opioids.

BACKGROUND: Opioid withdrawal symptoms are a highly salient and consequential health condition experienced by people who use opioids (PWUO). This study utilized qualitative interviews to explore opioid withdrawal experiences and consequences among PWUO in Los Angeles County, USA. METHODS: Semi-structured qualitative interviews were conducted with 22 PWUO (aged 27-63 years) between May 2021 and May 2022. Participants self-reported opioid and injection drug use in the last 30 days. We employed an inductive thematic approach to systematically code and synthesize textual interview data. RESULTS: Participants experienced withdrawal symptoms frequently, with many going to great lengths to avoid them. Withdrawal pain was described as incapacitating and interfered with PWUO's ability to sustain regular employment and ensure stable housing. Avoiding withdrawal was described as influential in driving decisions to continue using opioids. Mechanisms for managing withdrawal included using other substances to the point of sedation. PWUO who transitioned from heroin to fentanyl use revealed more frequent, painful, and faster onset of withdrawal symptoms. Adverse withdrawal experiences and fear of precipitated withdrawal from buprenorphine were barriers to treatment initiation and continuation. CONCLUSION: Withdrawal symptoms among PWUO increase health risk. Improved strategies to treat opioid withdrawal are urgently needed. Solutions such as safe supply and intentional opioid withdrawal interventions (educational trainings, withdrawal comfort kits) are needed to improve withdrawal management and reduce opioid-related harm.

Updates on syringe coverage and service uptake among needle and syringe programs in the United States, 2019-2020.

BACKGROUND: As injection drug use has increased in the US, so too has the prevalence of receptive syringe sharing. Since the 1980s, Needle and Syringe Programs (NSPs) have been an important source of clean injection equipment and disposal of used syringes. This study reports national syringe coverage and examines the impact of program attributes on organizational-level service uptake, defined as number of syringes distributed per participant contact per year. METHODS: In 2019 and 2020, we administered an annual cross-sectional survey to NSPs operating in the US (n = 260). A national estimate of coverage was calculated by dividing the total number of syringes distributed by the 2019 and 2020 population estimate of people who inject drugs (PWID). Frequency distributions and percentages were calculated for categorical variables (e.g., funding, census region, distribution policy/modality), and median and interquartile ranges (IQR) were calculated for continuous variables (e.g., participant contacts, syringes distributed). Bivariate and multivariable mixed effects logistic regression models were used to estimate the odds ratio associated with organizational characteristics on increasing service uptake at the NSP level. RESULTS: From 2019 to 2020, the total number of participant contacts by NSPs increased from 871,976 to 898,891, and the number of syringes distributed increased from 92,648,529 to 113,071,748. The national coverage estimate increased from 29.5 (95 % CI = 15.0, 58.2) to 35.8 (95 % CI = 18.2, 70.6) syringes per PWID. Fifty-eight percent of NSPs increased service uptake in 2020 as compared to the previous year. NSPs that received government funding and NSPs that changed to a less restrictive syringe distribution policy were more likely to increase service uptake (aOR 1.80, 95 % CI = 1.01, 3.22 and aOR 3.33, 95 % CI = 1.11, 9.94, respectively). Syringe distribution modalities also diversified, with more NSPs reaching participants via backpacking/outreach, fixed site pop-ups, mobile delivery, mail-based delivery, leaving supplies out, and secondary distribution. CONCLUSION: Both governmental investment in harm reduction programming and needs-based distribution of syringes increased service uptake and thus should be expanded and sustained to reduce harms associated with injection drug use.

Health risks associated with smoking versus injecting fentanyl among people who use drugs in California.

BACKGROUND: Given the attention, funding, and services that seek to reduce overdose mortality from fentanyl, it is important to understand whether a potential solution is for more people to switch from injecting to smoking fentanyl. As such, we set out to conduct a study to compare health and healthcare utilization outcomes associated with different modes of illicit fentanyl administration. METHODS: From January to February 2023, we recruited people who use drugs from 34 syringe services programs across California, USA (N=999) and surveyed their substance use, health outcomes, and healthcare utilization. We compared health risks among people who injected fentanyl (78% of whom also smoked) to people who solely smoked fentanyl (n=563). RESULTS: Of the 563 participants, forty-one percent injected fentanyl and 59% only smoked fentanyl. People who injected fentanyl were 40% more likely to have experienced a non-fatal overdose in the past 3 months (27% vs. 19%; aRR=1.40; 95% CI=1.03, 1.93) and 253% more likely to have had a skin and soft tissue infection in the past 3 months (39% vs. 15%; aRR=2.53; 95% CI=1.74, 3.67), compared to people who only smoked fentanyl. The average number of nights spent in the hospital was higher among people who injected fentanyl (average 1.2 nights vs. 0.7 nights; aIRR=1.78; 95% CI=1.02, 3.09; p=0.04).There were non-significant associations between mode of fentanyl administration and number of emergency department visits and probability of hospitalization. CONCLUSIONS: Findings suggested that people who injected fentanyl were at higher risk for overdose and skin and soft tissue infections than people who only smoked fentanyl. Distribution of safe smoking supplies may facilitate transitions from injecting to smoking fentanyl, thereby reducing health risks associated with fentanyl use.

Availability of telehealth-based services at syringe services programs under the COVID-19 Public Health Emergency.

INTRODUCTION: The expanded capacity of syringe services programs (SSPs) in the USA to integrate telehealth services was largely related to flexibility of buprenorphine prescription in response to the COVID-19 pandemic. SSPs demonstrated the potential of using telehealth to reach participants with both medical and non-medical services. The present study examines the implementation of medical and non-medical telehealth-based health services in 2020 at SSPs in the USA and organizational characteristics associated with adopting specific telehealth services. METHODS: We administered a cross-sectional survey among all known SSPs operating in the USA as of 2021. The two primary study outcomes were (1) implementation of medical telehealth and (2) implementation of non-medical telehealth in 2020. Medical services included HIV counseling/care, hepatitis C virus (HCV) counseling/care, and buprenorphine. Non-medical services included wellbeing/check-ins, overdose prevention training, health navigation, harm reduction and psychological counseling. Bivariate and multivariable mixed effects logistic regression models were used to directly estimate the odds ratio associated with organizational characteristics on the implementation of telehealth-based health services. RESULTS: Thirty percent of programs (n = 290) reported implementing telehealth-based health services. In multivariable logistic regression models, community-based organization SSPs had higher odds of implementing medical (aOR = 4.69, 95% CI [1.96, 11.19]) and non-medical (aOR = 2.18, 95% CI [1.10, 4.31]) health services compared to public health department SSPs. SSPs that received governmental funding had higher odds of implementing medical services via telehealth (aOR = 2.45, 95% CI [1.35, 4.47]) compared to programs without governmental funding. CONCLUSION: Community-based organization SSPs and those with government funding had the highest odds of telehealth implementation in response to the COVID-19 Public Health Emergency. Federal, state, and local governments must increase funding for low-barrier venues like SSPs to support telehealth implementation to serve the needs of people who use drugs.

Impact of a high-volume overdose prevention site on social and drug disorder in surrounding areas in San Francisco.

BACKGROUND: Between January and December 2022 a multi-service center incorporating an overdose prevention site (OPS) operated with city government sanction in San Francisco. One concern often expressed about OPS is that they may increase social nuisance associated with drug use in the surrounding area, despite international evidence that this is not the case. METHODS: We conducted systematic street observation of 10 indicators of drug- and homelessness-related social nuisance in a 500 m radius around the OPS and around a comparison point in the same city before and after the introduction of the OPS. We estimated the risk that any given street within sampling areas would have nuisance post-intervention relative to the control area using Poisson regression. RESULTS: Ratio of relative risks of any reported nuisance in the 500 m area surrounding the OPS from pre- to post-intervention to that of the comparison area was 0.69 (95% CI: 0.54, 0.87; p=0.002). The relative risk of drug-specific nuisance was similar to the comparison area pre/post intervention (0.90; 95% CI 0.66, 1.24; p=0.53). The risk of homelessness-specific nuisance decreased around the OPS (RR 0.7., 95% CI 0.52, 0.93; p=0.02) whereas they increased around the comparison area (RR 1.33, 95% CI 1.06, 1.68; p=0.02). CONCLUSION: We found that implementing authorized OPS services in a U.S. city did not increase the prevalence of visible signs of drug use and homelessness in the surrounding area. These findings are similar to those found at OPS outside the U.S.

Evaluating oxygen monitoring and administration during overdose responses at a sanctioned overdose prevention site in San Francisco, California: A mixed-methods study.

BACKGROUND: Overdose prevention sites (OPSs) are spaces where individuals can use pre-obtained drugs and trained staff can immediately intervene in the event of an overdose. While some OPSs use a combination of naloxone and oxygen to reverse overdoses, little is known about oxygen as a complementary tool to naloxone in OPS settings. We conducted a mixed methods study to assess the role of oxygen provision at a locally sanctioned OPS in San Francisco, California. METHODS: We used descriptive statistics to quantify number and type of overdose interventions delivered in 46 weeks of OPS operation in 2022. We used qualitative data from OPS staff interviews to evaluate experiences using oxygen during overdose responses. Interviews were coded and thematically analyzed to identify themes related to oxygen impact on overdose response. RESULTS: OPS staff were successful in reversing 100% of overdoses (n = 333) during 46 weeks of operation. Oxygen became available 18 weeks after opening. After oxygen became available (n = 248 overdose incidents), nearly all involved oxygen (91.5%), with more than half involving both oxygen and naloxone (59.3%). Overdoses involving naloxone decreased from 98% to 66%, though average number of overdoses concomitantly increased from 5 to 9 per week. Interviews revealed that oxygen improved overdose response experiences for OPS participants and staff. OPS EMTs were leaders of delivering and refining the overdose response protocol and trained other staff. Challenges included strained relationships with city emergency response systems due to protocol requiring 911 calls after all naloxone administrations, inconsistent supplies, and lack of sufficient staffing causing people to work long shifts. CONCLUSIONS: Although the OPS operated temporarily, it offered important insights. Ensuring consistent oxygen supplies, staffing, and removing 911 call requirements after every naloxone administration could improve resource management. These recommendations may enable success for future OPS in San Francisco and elsewhere.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial.

BACKGROUND: More than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxone's ability to improve naloxone distribution in general and among BIPOC specifically. METHODS: We will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxone's ability to improve SSPs' naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness. DISCUSSION: This trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.

"All carrots and no stick": Perceived impacts, changes in practices, and attitudes among law enforcement following drug decriminalization in Oregon State, USA.

BACKGROUND: By passing Ballot Measure 110 (BM 110), Oregon became the first U.S. state to decriminalize noncommercial possession of drugs that are illegal under the Controlled Substances Act. This study examined the perceived impacts of BM 110 on law enforcement and Oregon communities. METHODS: Our team visited four geographically distinct Oregon counties in August 2022 (two urban, two rural). The qualitative study involved conducting 34 hour-long interviews with law enforcement, other criminal legal system personnel, and representatives from emergency medical services/fire and substance use treatment and harm reduction agencies. Interviewees were asked about their perceptions of BM 110's effects on law enforcement, their communities, and agencies. RESULTS: Law enforcement interviewees viewed BM 110 as a failure; they perceived it resulted in an erosion of their authority. They expressed frustration that they could not use drug possession as a "tool" for investigations to pursue and build cases, establish probable cause, and impose what they believed necessary for social order. Law enforcement personnel in all four counties indicated they routinely seized drugs and drug paraphernalia during encounters with people using drugs, even when that was the only offense being committed. Police lacked knowledge that BM 110 included support for harm reduction services, housing assistance, and employment support. Law enforcement personnel had different opinions and practices regarding issuing Class E violations; those who did not issue them viewed them as a waste of time because they are not entry points into the criminal legal system. CONCLUSION: This study provides insights into drug decriminalization in Oregon. This examination is critical for informing BM 110's continued implementation as Oregon proceeds with increased treatment and support service provision. Our findings have important implications regarding other states' design and implementation of drug policy alternatives, including ones that remove law enforcement's role in addressing drug use.