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.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQß1.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQß1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQß1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQß1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQß1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQß1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

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).

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.

Optimizing naloxone distribution to prevent opioid overdose fatalities: results from piloting the Systems Analysis and Improvement Approach within syringe service programs.

BACKGROUND: Opioid overdose fatalities are preventable with timely administration of naloxone, an opioid antagonist, during an opioid overdose event. Syringe service programs have pioneered naloxone distribution for potential bystanders of opioid overdose. The objective of this study was to pilot test a multi-component implementation strategy-the systems analysis and improvement approach for naloxone (SAIA-Naloxone)-with the goal of improving naloxone distribution by syringe service programs. METHODS: Two syringe service programs participated in a 6-month pilot of SAIA-Naloxone, which included (1) analyzing program data to identify gaps in the naloxone delivery cascade, (2) flow mapping to identify causes of attrition and brainstorm programmatic changes for improvement, and (3) conducting continuous quality improvement to test and assess whether modifications improve the cascade. We conducted an interrupted time series analysis using 52 weeks of data before and 26 weeks of data after initiating SAIA-Naloxone. Poisson regression was used to evaluate the association between SAIA-Naloxone and the weekly number of participants receiving naloxone and number of naloxone doses distributed. RESULTS: Over the course of the study, 11,107 doses of naloxone were distributed to 6,071 participants. Through SAIA-Naloxone, syringe service programs prioritized testing programmatic modifications to improve data collection procedures, proactively screen and identify naloxone-naïve participants, streamline naloxone refill systems, and allow for secondary naloxone distribution. SAIA-Naloxone was associated with statistically significant increases in the average number of people receiving naloxone per week (37% more SPP participants; 95% CI, 12% to 67%) and average number of naloxone doses distributed per week (105% more naloxone doses; 95% CI, 79% to 136%) beyond the underlying pre-SAIA-Naloxone levels. These initial increases were extended by ongoing positive changes over time (1.6% more SSP participants received naloxone and 0.3% more naloxone doses were distributed in each subsequent week compared to the weekly trend in the pre-SAIA Naloxone period). CONCLUSIONS: SAIA-Naloxone has strong potential for improving naloxone distribution from syringe service programs. These findings are encouraging in the face of the worsening opioid overdose crisis in the United States and support testing SAIA-Naloxone in a large-scale randomized trial within syringe service programs.

A national survey of law enforcement post-overdose response efforts.

Background: Law enforcement agencies in the US have provided naloxone to officers and developed initiatives to follow-up after a non-fatal overdose. However, the prevalence and characteristics of these efforts have yet to be documented in research literature.Objectives: We sought to understand the national prevalence of naloxone provision among law enforcement and examine the implementation of post-overdose follow-up.Methods: We administered a survey on drug overdose response initiatives using a multimodal approach (online and mail) to a nationally representative sample of law enforcement agencies (N = 2,009; 50.1% response rate) drawn from the National Directory of Law Enforcement Administrators database. We further examine a subsample of agencies (N = 1,514) that equipped officers with naloxone who were also asked about post-overdose follow-up.Results: We found 81.7% of agencies reported officers were equipped with naloxone; among these, approximately one-third (30.3%) reported follow-up after an overdose. More than half (56.8%) of agencies indicated partnership in follow-up with emergency medical services as the most common partner (68.8%). There were 21.4% of agencies with a Quick Response Team, a popular national post-overdose model, and were more likely to indicate partnership with a substance use disorder treatment provider than when agencies were asked generally about partners in follow-up (74.5% and 26.2% respectively).Conclusion: Many law enforcement agencies across the US have equipped officers with naloxone, and about one-third of those are conducting follow-up to non-fatal overdose events. Post-overdose follow-up models and practices vary in ways that can influence treatment engagement and minimize harms against persons who use drugs.

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.

How do contextual factors influence naloxone distribution from syringe service programs in the USA: a cross-sectional study.

BACKGROUND: Naloxone is a medication that can quickly reverse an opioid overdose. Syringe service programs (SSPs) are community-based prevention programs that provide a range of evidence-based interventions in the USA, including naloxone distribution. Attributes of SSPs make them ideal settings for naloxone distribution-they have staff and delivery models that are designed to reach people who use drugs where they are. We assessed which outer and inner setting factors of SSPs were associated with naloxone distribution in the USA. METHODS: We surveyed SSPs in the USA known to the North American Syringe Exchange Network in 2019. Using the exploration, preparation, implementation and maintenance framework, we assessed inner and outer contextual factors associated with naloxone distribution among SSPs (n = 263 or 77% of SSPs). We utilized negative binomial regression to assess which factors were associated with the number of naloxone doses distributed and people receiving naloxone. RESULTS: SSPs reported distributing 710,232 naloxone doses to 230,506 people in the prior year. Regarding outer setting, SSPs located in areas with high levels of community support had a higher level of naloxone distribution (aIRR = 3.07; 95% confidence interval (CI): 2.09-4.51; p < 0.001) and 110% (p = 0.022) higher rate of people receiving naloxone (aIRR = 2.10; 95% CI 1.46-3.02; p < 0.001) in the past 12 months. The legal status of SSPs and the level of need was not significantly associated with naloxone distribution. Regarding inner setting, SSPs with proactive refill systems (aIRR = 2.08; 95% CI 1.27-3.41; p = 0.004), greater number of distribution days (aIRR = 1.09 per day; 95% CI 1.06-1.11; p < 0.001) and older programs (aIRR = 1.06 per year; 95% CI 1.02-1.11; p = 0.004) were associated with higher levels of naloxone distribution. Also, SSPs with proactive refill systems (aIRR = 2.23; 95% CI 1.38-3.58; p = 0.001); greater number of distribution days (aIRR = 1.04; 95% CI 1.02-1.07; p < 0.001) and older programs (aIRR = 1.11; 95% CI 1.05-1.17; p < 0.001) were associated with a higher number of people receiving naloxone. CONCLUSION: We identified outer and inner setting factors of SSPs that were associated with greater naloxone distribution. It is critical to ensure SSPs are adequately resourced to build community support for services and develop service delivery models that maximize naloxone distribution to address the nation's opioid overdose crisis.

Population-Level Health Effects of Involuntary Displacement of People Experiencing Unsheltered Homelessness Who Inject Drugs in US Cities.

Importance: At least 500 000 people in the US experience homelessness nightly. More than 30% of people experiencing homelessness also have a substance use disorder. Involuntary displacement is a common practice in responding to unsheltered people experiencing homelessness. Understanding the health implications of displacement (eg, "sweeps," "clearings," "cleanups") is important, especially as they relate to key substance use disorder outcomes. Objective: To estimate the long-term health effects of involuntary displacement of people experiencing homelessness who inject drugs in 23 US cities. Design, Setting, and Participants: A closed cohort microsimulation model that simulates the natural history of injection drug use and health outcomes among people experiencing homelessness who inject drugs in 23 US cities. The model was populated with city-level data from the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system and published data to make representative cohorts of people experiencing homelessness who inject drugs in those cities. Main Outcomes and Measures: Projected outcomes included overdose mortality, serious injection-related infections and mortality related to serious injection-related infections, hospitalizations, initiations of medications for opioid use disorder, and life-years lived over a 10-year period for 2 scenarios: "no displacement" and "continual involuntary displacement." The population-attributable fraction of continual displacement to mortality was estimated among this population. Results: Models estimated between 974 and 2175 additional overdose deaths per 10 000 people experiencing homelessness at 10 years in scenarios in which people experiencing homelessness who inject drugs were continually involuntarily displaced compared with no displacement. Between 611 and 1360 additional people experiencing homelessness who inject drugs per 10 000 people were estimated to be hospitalized with continual involuntary displacement, and there will be an estimated 3140 to 8812 fewer initiations of medications for opioid use disorder per 10 000 people. Continual involuntary displacement may contribute to between 15.6% and 24.4% of additional deaths among unsheltered people experiencing homelessness who inject drugs over a 10-year period. Conclusion and Relevance: Involuntary displacement of people experiencing homelessness may substantially increase drug-related morbidity and mortality. These findings have implications for the practice of involuntary displacement, as well as policies such as access to housing and supportive services, that could mitigate these harms.

Reduced Emergency Department Visits and Hospitalisation with Use of an Unsanctioned Safe Consumption Site for Injection Drug Use in the United States.

BACKGROUND: Safe consumption sites (SCS) are an evidence-based intervention to prevent drug use-related harm. In late 2014, an organisation in an undisclosed location in the USA opened an unsanctioned SCS. OBJECTIVE: To evaluate whether use of the unsanctioned SCS affected medical outcomes. DESIGN: A prospective cohort study. SETTING: Neighbourhoods surrounding the SCS. PARTICIPANTS: People who injected drugs were recruited and interviewed at baseline and 6 and 12 months from 2018 to 2020. INTERVENTION: People using the SCS could bring pre-obtained drugs to consume via injection, which were monitored by trained staff with naloxone. MAIN MEASURES: Any overdose, number of non-fatal overdoses, skin and soft tissue infections, emergency department utilisation, number of emergency department visits, hospitalisation and number of nights spent in hospital. KEY RESULTS: A total of 494 participants enrolled in the study; 59 (12%) used the SCS at least once. We used propensity score weighting to analyse the association between SCS utilisation and measures. People using the SCS were 27% (95% CI: 12-46%) less likely to visit the emergency department, had 54% (95% CI: 33-71%) fewer emergency department visits, were 32% (95% CI: 4-57%) less likely to be hospitalised, and spent 50% (95% CI: 1-85%) fewer nights in hospital. Though not significant, people using the SCS had a lower likelihood of overdosing and slightly higher likelihood of skin and soft tissue infections. CONCLUSIONS: Our findings support the use of SCS in the USA to reduce the growing burden of acute care service utilisation related to injection drug use.

Establishment and Enforcement of Operational Rules at an Unsanctioned Safe Drug Consumption Site in the United States, 2014-2020.

Objectives. To examine how operational rules are established and enforced at an unsanctioned safe consumption site (SCS) operating in the United States. Methods. We conducted 44 qualitative interviews with people who use drugs, staff members, and volunteers at an unsanctioned SCS and analyzed them using an inductive thematic approach. Results. Rule-making processes were largely driven by concerns raised by service users rather than driven by external pressures, and iterated rapidly in response to changing needs. The unsanctioned nature of the site produced an environment where bottom-up rule-making was critical to generating a shared sense of ownership of the site and where enforcement was necessarily fluid. Conclusions. Removing external restrictions on operational rules for SCSs results in a flexible set of rules that are highly responsive to the social and public health needs of people who use drugs. Legislation and regulations of SCSs should aim to place as few hard limits on operating conditions as possible to maximize involvement of and responsiveness to people who use drugs. (Am J Public Health. 2022;112(S2):S166-S172. https://doi.org/10.2105/AJPH.2022.306714).

Factors Associated with Likelihood of Initiating Others into Injection Drug Use Among People Who Inject Drugs in West Virginia.

People who inject drugs (PWID) play a critical role in injection-naïve individuals transitioning to injection drug use. We investigated factors associated with future likelihood of initiating injection-naïve individuals using multivariable logistic regression among 418 PWID in rural Appalachia (Cabell County, West Virginia). Less than 10% reported they were likely to initiate someone in the future. Acquiring syringes from a syringe services program was associated with decreased odds of being likely to initiate someone in the future (adjusted odds ratio [aOR] 0.46, 95% CI 0.23, 0.95), while having previously initiated someone into injection drug use was associated with increased odds (aOR 8.65, 95% CI 4.07, 18.41). Among our sample of PWID in Appalachia, a small proportion reported that they would be likely to initiate an injection-naïve individual in the future. Efforts to reduce injection initiation assistance should focus on this subpopulation of PWID who indicate a willingness to engage in this behavior.

Predictors of protein intake among people who inject drugs in Los Angeles and San Francisco, California.

BACKGROUND AND OBJECTIVES: While inadequate nutrition can weaken the immune system and lead to negative health sequelae for vulnerable populations, little is known about nutritional intake among people who inject drugs (PWID). We aimed to quantify nutritional intake among PWID and to explore associations between protein intake and drug use. METHODS: A cross-sectional design was used to analyze self-reported participant data. PWID were recruited from community settings in California in 2016/2017. Participants reported on food consumption per day for a 30-day period, from which a continuous protein intake variable was created. RESULTS: Modal characteristics of participants (N = 937) were: white (42.5%), male (75.3%), healthy body mass index (BMI) (56.6%), and unhoused (82.9%). Less than 1% of participants met or exceeded recommended guidelines for protein intake (0.80 g/day/1 kg body weight). The final multiple regression model found protein intake to be significantly positively associated with older age, high school or greater education, frequency of opiate and marijuana use, while Latinx ethnicity was inversely associated with protein intake, adjusting for gender. DISCUSSION AND CONCLUSIONS: Our study shows PWID are generally not underweight, yet they are grossly protein deficient, which can be harder to recognize. Poverty, homelessness, and other structural barriers likely contribute to this issue, which demonstrates the need for communities to provide more access to nutrient-rich food to PWID. SCIENTIFIC SIGNIFICANCE: Our study demonstrates the novel findings that opiate and marijuana use frequency, but not stimulants (methamphetamine and cocaine) may increase preference for protein-rich foods among PWID.

Health risk associated with residential relocation among people who inject drugs in Los Angeles and San Francisco, CA: a cross sectional study.

BACKGROUND: Given the housing instability and frequent residential relocation (both volitional and hegemonic) of people who inject drugs, we sought to determine whether residential relocation (defined as sleeping in a different place in the past 30 days) is associated with health outcomes in a sample of people who inject drugs (PWID). METHODS: We recruited 601 PWID using targeted sampling and interviewed them between 2016 and 2018 in San Francisco and Los Angeles, CA about housing, drug use practices, and service utilization. We then developed multivariable regression models to investigate how residential relocation is associated with violence, health outcomes, and social service access. We analyzed our data between June 2018 and October 2019. RESULTS: Participants who relocated in the past 30 days had lower odds of being in substance use treatment (Adjusted Odds Ratio [AOR] = 0.62, 95% Confidence Interval [CI] = 0.42, 0.89) and higher odds of nonfatal overdose (AOR = 2.50, CI = 1.28, 4.90), receptive syringe sharing (AOR = 2.26, CI = 1.18, 4.32), severe food insecurity (AOR = 1.69, CI = 1.14, 2.50), having belongings stolen (AOR = 2.14, CI = 1.42, 3.21), experiencing physical assault (AOR = 1.58, CI = 1.03, 2.43), arrest (AOR = 1.64, CI = 1.02, 2.65), and jail (AOR = 1.90, CI = 1.16, 3.13) in the past 6 months when compared to those who did not relocate. CONCLUSIONS: PWID who have relocated in the past 30 days have higher odds of experiencing violence and life- threatening adverse outcomes, and policies that disrupt living circumstances of PWID should be ended in favor of those that support housing stability.

Best practices for community-based overdose education and naloxone distribution programs: results from using the Delphi approach.

BACKGROUND: Opioid-related overdose deaths have surged in the USA over the last two decades. Overdose fatalities are preventable with the timely administration of naloxone. Syringe service programs (SSP) have pioneered community-based naloxone distribution through overdose prevention and naloxone distribution (OEND) programs. There is a dearth of information with regards to best practices for community-based OEND. METHODS: We utilized a modified Delphi approach to develop a set of best practices for OEND delivery. Starting with an initial list of best practices, we engaged 27 experts, in the field of OEND programming who reviewed, made recommendations for changes, and assigned a priority to each best practice. RESULTS: Two rounds of input resulted in a final list of 20 best practices organized into four categories. The mean priority scores ranged from 1.17 to 2.17 (range 1 to 3). The top 5 ranked best practices were ensuring that SSP participants have low barrier, consistent, needs-based access to naloxone and that there is ample naloxone available within communities. While the remaining fifteen best practices were deemed important, they had more to do with organizational culture and implementation climate. CONCLUSIONS: Increasing community-based OEND delivery is essential to reduce opioid overdose deaths; however, it will be insufficient to add programs without an eye toward quality of implementation and fidelity to the model upon which the evidence is based. This list of best practices summarizes the consensus among OEND experts and can serve as a tool for SSPs providing OEND programming to improve services.

Implementation and sustainability of safe consumption sites: a qualitative systematic review and thematic synthesis.

BACKGROUND: Safe consumption sites (SCSs) serve diverse populations of people who use drugs (PWUD) and public health objectives. SCS implementation began in the 1980s, and today, there are at least 200 known SCSs operating in over twelve countries. While a growing literature supports their effectiveness as a harm reduction strategy, there is limited information on contextual factors that may support or hinder SCS implementation and sustainability. We aimed to fill this gap in knowledge by reviewing existing qualitative studies on SCSs. METHODS: We conducted a systematic review and thematic synthesis of qualitative studies. We identified all peer-reviewed, English-language qualitative studies on SCSs containing original data in PubMed, Web of Science, Google Scholar, and Science Direct as of September 23, 2019. Two authors independently screened, abstracted, and coded content relating to SCS implementation and sustainment aligned with the Exploration, Preparation, Implementation, Sustainment (EPIS) implementation science framework. RESULTS: After removing duplicates, we identified 765 unique records, of which ten qualitative studies met inclusion criteria for our synthesis. Across these ten studies, 236 total interviews were conducted. Overall, studies described how SCSs can (1) keep drug use out of public view while fostering a sense of inclusion for participants, (2) support sustainment by enhancing external communities' acceptability of SCSs, and (3) encourage PWUD utilization. Most studies also described how involving PWUD and peer workers (i.e., those with lived experience) in SCS operation supported implementation and sustainability. DISCUSSION: Our thematic synthesis of qualitative literature identified engagement of PWUD and additional factors that appear to support SCS planning and operations and are critical to implementation success. However, the existing qualitative literature largely lacked perspectives of SCS staff and other community members who might be able to provide additional insight into factors influencing the implementation and sustainability of this promising public health intervention.

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

BACKGROUND: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. METHODS: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Correlates of Transactional Sex and Violent Victimization among Men Who Inject Drugs in Los Angeles and San Francisco, California.

Men who inject drugs (MWID) and engage in transactional sex (i.e., receive money or drugs in exchange for sex) are vulnerable to HIV and violence. However, MWID who engage in transactional sex have been less studied than women. We examine factors associated with transactional sex among MWID in Los Angeles and San Francisco and whether transactional sex is associated with violent victimization. MWID were recruited using targeted sampling methods in 2011-2013 and completed surveys that covered demographics, drug use, HIV risk, violence, transactional sex, and other items. Multivariable logistic regression was used to (1) determine factors independently associated with transactional sex and (2) determine if transactional sex was independently associated with violence victimization in the last 6 months among MWID. An interaction term between income source and sexual identity was included in the transactional sex model. Of the 572 male PWID in the sample, 47 (8%) reported transactional sex in the past 6 months. Self-reported HIV infection was 7% for MWID who did not report transactional sex, 17% for MWID who reported transactional sex, and 24% for MWID who reported transactional sex and reported gay or bisexual identity. In multivariable analysis, transactional sex was positively associated with gay or bisexual identity (GB without illegal income adjusted odds ratio [AOR] = 5.16; 95% confidence interval [CI] = 1.86-14.27; GB with illegal income AOR = 13.55, CI = 4.57-40.13), coerced sex in the last 12 months (AOR = 11.66, CI = 1.94-70.12), and violent victimization in the last 12 months (AOR = 2.31, CI = 1.13-4.75). Transactional sex was negatively associated with heroin injection (last 30 days) (AOR = 0.37; 95% CI = 0.18-0.78). Transactional sex was independently associated with violent victimization in the last 12 months (AOR = 2.04; 95% CI = 1.00-4.14) while controlling for confounders. MWID who engaged in transactional sex are at elevated risk for HIV and multiple forms of violent victimization. Interventions focused on this at-risk subpopulation are urgently needed and should include access to substance use disorder treatment, victimization services, and harm reduction services across the HIV care continuum.

Novel Routes of Potential Hepatitis C Virus Transmission among People Who Inject Drugs: Secondary Blood Exposures Related to Injection Drug Use.

BACKGROUND: The US is in the midst of a national Hepatitis C Virus (HCV) epidemic that appears to be driven by new cases among people who inject drugs (PWID). While HCV transmission among PWID is believed to occur mostly through direct sharing of syringes, some infections may be spread via secondary processes and materials involved in injecting. OBJECTIVES: Here, we present the prevalence of secondary blood exposures on clothing and nearby surfaces after injection episodes and examine the correlations of these exposures to lifetime HCV infection among a targeted sample of 553 PWID in Los Angeles and San Francisco, California in 2016-18. RESULTS: In multivariate logistic regression models, higher odds of blood on clothing in the last 30 days was significantly (p < 0.05) associated with lifetime positive HCV status, opioids as primary drug, injecting with others, sharing cookers, and receptive syringe sharing. Higher adjusted odds of blood on nearby surfaces in the last 30 days was significantly associated with lifetime positive HCV status, sharing cookers, and receptive syringe sharing. Native American race was associated with significantly lower adjusted odds of both outcome variables. Conclusions/Importance: Results indicate the relevance of physical and social micro-environments to the potential for blood exposures secondary to injection episodes. Individuals with chronic HCV seropositivity are potentially more likely to expose others to blood due to decreases in the blood's ability to clot. This highlights the need for increased HCV testing at harm reduction sites and increased supply of first aid and wound-care materials to help stop potential blood exposures after injection episodes.