Phillip Oliver Coffin

Background: Black and Latino people are at high risk for overdose mortality. Interventions focused on overdose risk behaviors may offer opportunities to reduce overdose, but little research has addressed racial and ethnic differences in risk behaviors. We explored differences in risk behaviors among Black, Latino, and White individuals who used opioids and had a history of prior overdose. Methods: We used cross-sectional baseline data from REBOOT 2.0 (the REpeated dose Behavioral intervention to reduce Opioid Overdose Trial) based in Boston, MA, and San Francisco, CA, which enrolled people with opioid use disorder and a history of opioid overdose. We used the Andersen behavioral model to inform covariate selection for a multivariable logistic regression analysis examining associations between race/ethnicity (Black, Latino, and White) and three individual overdose risk behaviors (using opioids alone, not using a tester dose, and using alcohol and/or benzodiazepines on the same day as opioids). Results: Of 247 participants, 19% were Black, 16% were Latino and 66% were White. More than 20% in each group reported each risk behavior. In unadjusted analyses, Black participants had higher odds of using alone (OR = 2.17, 95% CI 1.08–4.36) and lower odds of not using a tester dose (OR = 0.48, 95% CI 0.24–0.93), indicating greater tester dose use. After adjusting for age, gender and structural determinants of health (e.g., housing, incarceration, education, opioid use disorder treatment) the adjusted odds of Black participants using alone (aOR = 2.05, 95% CI 0.99–4.26) and a tester dose (aOR = 0.56, 95% CI 0.28–1.13) were no longer statistically significant. Conclusions: Overdose risk behaviors were common among Black, Latino, and White overdose survivors in San Francisco and Boston. Overdose risk behaviors were not significantly different for Black or Latino compared to White overdose survivors after adjusting for age, gender, and structural determinants of health. For individuals at the highest risk of overdose, individual prevention efforts remain necessary but are not sufficient. Interventions should also address the social-structural factors shaping overdose risk, including housing, criminalization, and access to treatment. Trial registration: Details found at clinicaltrials.gov, NCT02093559.

BACKGROUND: The underlying cause of deaths attributed to acute stimulant (methamphetamine or cocaine) toxicity is poorly understood, although cardiovascular events are believed to contribute. METHODS: We analyzed psychological autopsy data from acute stimulant toxicity deaths in San Francisco from 2022 to 2023. Sources included vital records, autopsies, medical records, and mixed-methods interviews with informants (eg, family and friends) who knew decedents in the year preceding death. We compared sociodemographic characteristics and cardiovascular measures (autopsy, ECG, echocardiogram, or laboratory abnormalities; diagnoses; acute care visits; symptoms) by fentanyl involvement. Age was skewed and compared with a Wilcoxon rank-sum test. Proportions were compared with χ ² or Fisher exact tests. Qualitative thematic analyses identified themes related to cardiovascular health in interviews. RESULTS: Among 101 deaths, 70 involved stimulants without opioids and 31 also involved fentanyl. Median age at death was higher among stimulant without opioids compared with fentanyl-involved decedents (58 versus 50 years; P =0.02). A plurality were White (44%), and 36% were Black. Most (69%) were unhoused or marginally housed. Cardiovascular conditions were identified in records among 93% of stimulant without opioids and 71% of fentanyl-involved decedents ( P P =0.02). Specific conditions more prevalent among stimulant without opioid decedents were cardiac enlargement ( P =0.04), coronary artery disease ( P =0.01), prolonged QTc interval ( P =0.03), and hypertension ( P =0.02). Themes from 140 informant interviews included family history of cardiovascular disease, cardiovascular symptoms, comorbid conditions, reluctance to seek care, and poor health contributing to social isolation. CONCLUSIONS: Premortem cardiovascular conditions and symptoms were common among stimulant decedents and were more prevalent among deaths attributed to stimulants without opioids compared with those involving fentanyl. In addition to opioid overdose prevention efforts, people who use stimulants might benefit from aggressive prevention and treatment of cardiovascular disease.

Background: There are no approved medications to treat methamphetamine use disorder. We conducted a phase 1b, inpatient,randomized, double-blind, placebo-controlled, within-subject crossover study to evaluate the safety of mirtazapine, a potential treatment for methamphetamine use disorder with positive phase 2 trial findings, in people receiving intravenous methamphetamine. Methods: Participants received mirtazapine 30 mg or placebo daily for 5 days, underwent an intravenous methamphetamine 30 mg challenge on day 5, followed by 2 days of washout, and then switched to the other study arm and received a second methamphetamine infusion at day 12. We monitored participants for adverse events, cardiovascular effects, and pharmacokinetics. Results: Participants (N = 15; 12 with no opioid use and 3 on methadone maintenance treatment) reached steady state mirtazapine levels before methamphetamine infusions. During the mirtazapine phase, participants reached methamphetamine peak plasma concentration 0.26 hours earlier than the placebo phase ( P = 0.02); no other impacts on methamphetamine pharmacokinetics were observed. Mirtazapine neither attenuated nor enhanced the expected cardiovascular effects of methamphetamine, including in participants receiving methadone maintenance therapy. Adverse events were similar between mirtazapine 30 mg and placebo. Conclusions: Mirtazapine 30 mg was safe and well-tolerated in people receiving a clinically relevant intravenous methamphetamine challenge, supporting further development of this medication for the treatment of methamphetamine use disorder.

Methamphetamine use is a driver of HIV among men who have sex with men (MSM) and is associated with suboptimal adherence to daily, oral PrEP. Long-acting PrEP may be a promising alternative. We analyzed data from the 2023 National HIV Behavioral Surveillance survey in four western cities to assess interest in long-acting PrEP among HIV-negative MSM participants. Of 1,450 participants, 7% used methamphetamine in the past 12 months. Two-thirds were interested in long-acting PrEP (68%); with no difference in interest (χ² = 1.4, p = 0.24) or prior PrEP use (χ² = 0.56, p = 0.46) by methamphetamine use. A larger proportion of participants unaware of PrEP had used methamphetamine (20% vs. 7%, χ² = 10.7, p < 0.01). Among those interested, a plurality preferred biannual injection (47%). We found high interest in long-acting PrEP and similar PrEP use rates, but lower awareness, among participants who used methamphetamine. However, our sample may not have been representative of those with higher-risk methamphetamine use.

Background: Stimulants, including cocaine and methamphetamine, are associated with HIV transmission and viremia. Contingency management (CM), which provides financial incentives for non-reactive urine testing, is first-line treatment for stimulant use disorder (StUD), yet has been minimally studied or integrated into HIV care. Methods: We conducted a 12-week, single-arm implementation-effectiveness pilot of weekly CM in a safety-net HIV clinic for living with HIV (PWH) who have StUD. Participants received escalating incentives for stimulant-negative and/or tenofovir-reactive point-of-care urine assays. Using the RE-AIM framework, we evaluated Reach (demographics, attendance), Effectiveness (stimulant-negative/tenofovir-positive tests, HIV virologic suppression [VS]), and Implementation. We conducted semi-structured, in-depth participant interviews following intervention completion to explore perceived impact and implementation. Results: From September 2023 to February 2024, we enrolled 31 PWH with StUD: 77% used methamphetamine, 35% cocaine, and 19% fentanyl. Only 17/31 (55%) had VS at baseline. Participants attended a mean of 5/12 visits (42%). Among PWH who attended post-enrollment visits (26/31), 61/110 (56%) stimulant tests were negative and 98% (89/91) of tenofovir tests were positive. Post-intervention, 88% (23/26) of retained participants achieved VS (p<0.01). Qualitative interviews revealed factors enhancing Reach (embedding CM within HIV care), Effectiveness (incentives supporting adherence self-efficacy; program providing structure and motivation), and Implementation (supportive staff relationships, non-judgmental approach). Conclusions: Contingency management for stimulant use and/or ART adherence (using point-of-care tenofovir assays) embedded into HIV care was associated with reduced stimulant use and gains in viral suppression. Scalability of integrating HIV and stimulant use disorder management using CM merits further evaluation.

Background and aims: The emergence of fentanyl in the street market for opioids has limited the benefits of some interventions to manage opioid overdose; thus, preventing the occurrence of opioid overdose is essential. We tested a behavioral intervention shown to prevent heroin overdose in a pilot study, in two United States cities with prevalent fentanyl. Design: Phase III two‐site single‐blinded randomized controlled trial of a repeated dose motivational interviewing intervention to reduce overdose (REBOOT) versus attention control, over 16 months from 2019 to 2023. Setting: San Francisco, California, and Boston, Massachusetts, USA. Participants: 18–65 years of age, with opioid use disorder (OUD), active non‐prescribed opioid use, opioid overdose within 3 years and prior receipt of take‐home naloxone. A total of 268 participants were randomized (50% intervention, 50% control), 62% of whom were male, 15% Latine, 65% White and 14% Black/African American; 95% had used fentanyl. Intervention: Motivational interviewing review of experienced and witnessed overdose and development of personal prevention plan, administered at months 0, 4, 8 and 12. Measurements: TimeLine FollowBack of interval overdose events and covariates, administered prior to the intervention at months 0, 4, 8, 12 and 16. Primary outcome was occurrence of any nonfatal or fatal overdose event. Findings: There were no significant effects of REBOOT compared with control on the primary outcome of occurrence of any overdose [relative risk (RR) = 0.94, 95% confidence interval (CI) = 0.79–1.11, P = 0.45] or secondary outcome of the number of overdose events (RR = 0.80, 95% CI = 0.6–1.06, P = 0.12). Results did not differ when excluding data collected during the first 12 months of the COVID‐19 pandemic. Compared with control, REBOOT was not associated with days in OUD treatment and not using opioids (RR = 0.94, 95% CI = 0.88–1.00, P = 0.06). In post‐hoc analysis, REBOOT was associated with fewer overdose events among participants with no past 4‐month overdose at baseline (RR = 0.70, 95% CI = 0.51–0.97, P = 0.03). Conclusion: A repeated dose motivational interviewing intervention to reduce overdose had no statistically significant effect on opioid overdose in two US cities where fentanyl was the dominant street opioid.