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This multi\u2010site study explores trends in opioid initiation in three US cities and associations with sociodemographic factors, current drug use and overdose risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Methods<\/jats:title><jats:p>We analysed survey data from a cross\u2010sectional study of PWUO in Baltimore, Maryland (<jats:italic>n<\/jats:italic> =\u2009173), Boston, Massachusetts (<jats:italic>n<\/jats:italic> =\u200980) and Providence, Rhode Island (<jats:italic>n<\/jats:italic> =\u200975). Age of first exposure to PO, NMPO and heroin was used to calculate opioid of initiation, and multinomial regression was employed to explore correlates of initiating with each.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010three percent of PWUO initiated with heroin, 24% with PO, 18% with NMPO and 24% with multiple opioids in their first year of use. We observed a reduction in heroin initiation and gradual replacement with PO\/NMPO over time. Women were more likely to initiate with NMPO [relative risk ratio (RRR) 2.4; 95% confidence interval (CI) 1.1, 5.0], PO (RRR 2.2, 95% CI 1.1, 4.4) or multiple opioids (RRR 2.1, 95% CI 1.1, 4.2), than heroin. PWUO initiating with NMPO had significantly higher current benzodiazepine use, relative to those initiating with heroin (RRR 3.2, 95% CI 1.4, 7.4), and a high prevalence of current fentanyl use (30%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusions<\/jats:title><jats:p>Our study highlights women and PWUO initiating with NMPO as key risk groups amid the changing landscape of opioid use and overdose, and discusses implications for targeted prevention and treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dar.13060","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T07:44:20Z","timestamp":1586159060000},"page":"375-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Trends in opioid initiation among people who use opioids in three US cities"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3801-1082","authenticated-orcid":false,"given":"Saba","family":"Rouhani","sequence":"first","affiliation":[{"name":"Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health  Baltimore USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Nyeong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health  Baltimore USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth B.","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health  Baltimore USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Traci C.","family":"Green","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research Excellence on Opioids and Overdose Rhode Island Hospital  Providence USA"},{"name":"Alpert Medical School Brown University  Providence USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan G.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health  Baltimore USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"unstructured":"CDC. 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