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This pattern presents specific risks for people at risk for and living with HIV, who have high rates of stimulant use and disproportionate risk of opioid overdose due to unintentional fentanyl use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study objectives<\/jats:title>\n                    <jats:p>This pilot randomized controlled trial evaluates intramuscular naltrexone as a novel biomedical strategy for opioid overdose prevention among people who use stimulants living with or at risk for HIV. The primary outcome is acceptability; secondary outcomes include effectiveness and safety; and an exploratory outcome characterizes patterns of opioid exposure among people reporting only stimulant use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention design<\/jats:title>\n                    <jats:p>: The NOD (Naltrexone for Overdose Prevention) Study will randomize 100 participants 1:1 to receive intramuscular naltrexone (380\u00a0mg) every 4 weeks or usual care for 24 weeks. Both arms will receive harm reduction services for overdose prevention including intranasal naloxone and safer consumption supplies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Acceptability (primary outcome) will be assessed quantitatively through retention at 24 weeks and proportion of on-time injections, and qualitatively through in-depth interviews (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200935). Effectiveness (secondary outcome) includes incident opioid overdose events requiring medical attention or community naloxone. Safety includes grade 2 or higher adverse events. Opioid exposure patterns (exploratory outcome) will be assessed through monthly urine toxicology, hair samples analyzed via liquid chromatography\/mass spectrometry, and Timeline Followback interviews. Analysis will use Kaplan-Meier methods for time-to-event outcomes and mixed methods for implementation evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study leverages the concept of HIV pre-exposure prophylaxis to the prevention of overdose by evaluating the viability of naltrexone as protection against opioid overdose. Success would demonstrate acceptability of long-acting opioid overdose prevention in people who use stimulants, while providing critical insights into implementation and impact of naltrexone as overdose prevention, as well as evaluating patterns of unintentional opioid use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13722-025-00623-5","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:24:35Z","timestamp":1765819475000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The NOD (Naltrexone for Overdose Prevention) study protocol: a pilot randomized controlled trial of intramuscular naltrexone for opioid overdose prevention among people who use stimulants living with or at risk for HIV"],"prefix":"10.1186","volume":"21","author":[{"given":"Ayesha","family":"Appa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xochitl Luna","family":"Marti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Baral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Shoptaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Bazazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Spinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Glidden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Gandhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Coffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"623_CR1","unstructured":"Drug Overdose Death Rates | National Institute on Drug Abuse (NIDA). 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