{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:25:08Z","timestamp":1787041508584,"version":"build-2736575974"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["112-S0023"],"award-info":[{"award-number":["112-S0023"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Both ceftriaxone (CRO) and doxycycline demonstrate activity against Treponema pallidum and bacteria causing sexually transmitted infections (STIs); however, the efficacy of their combination in a shorter duration remains unclear. We compared single-dose, 1-g CRO plus 7-day doxycycline (CRO\/Doxy) with single-dose, 2.4-MU benzathine penicillin G plus 7-day doxycycline (BPG\/Doxy) in treating early syphilis among people with HIV (PWH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this pilot randomized clinical trial, eligible participants were randomized to receive CRO\/Doxy or BPG\/Doxy. Rapid plasma reagin (RPR) titers were determined at baseline and at weeks 4, 12, 24, 36 and 48. PCR assays were conducted at baseline and at week 4 to detect T. pallidum and other STI-causing bacteria in oral rinse, urethral swab, and rectal swab samples to assess microbiologic responses. The primary outcome was the serologic responses of syphilis, defined as a 4-fold or greater decline of RPR titer at week 24.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From March 2023 to September 2024, 56 and 53 PWH with early syphilis were randomized to receive CRO\/Doxy and BPG\/Doxy, respectively. At baseline, 31.2% (n = 34) had chlamydia, 13.8% (n = 15) gonorrhea, and 6.4% (n = 7) Mycoplasma genitalium coinfection. In the ITT analysis, compared to the participants receiving BPG\/Doxy, those receiving CRO\/Doxy showed a lower serologic response rate at 24 weeks (60.7% vs 75.5%; difference, \u221214.8 percentage points; 95% CI, \u221232.0 to 2.5). The microbiologic response rates of syphilis, chlamydia, and M. genitalium infection were comparable between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the ITT analysis, CRO\/Doxy was not noninferior to BPG\/Doxy for early syphilis treatment among PWH at 24 weeks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag483","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T12:03:06Z","timestamp":1785585786000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-dose Ceftriaxone Plus 7-Day Doxycycline Versus Single-dose Benzathine Penicillin G Plus 7-Day Doxycycline in the Treatment of Early Syphilis in People With HIV: a Pilot Randomized Noninferiority Trial"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2825-8534","authenticated-orcid":false,"given":"Tzong-Yow","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch , Yunlin ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-5345","authenticated-orcid":false,"given":"Kuan-Yin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-7721","authenticated-orcid":false,"given":"Hsin-Yun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-5709","authenticated-orcid":false,"given":"Yu-Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Da","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristine","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Huei","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hsin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ching","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-0836","authenticated-orcid":false,"given":"Chien-Ching","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch , Yunlin ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]},{"name":"Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"2026081803365210300_ofag483-B1","doi-asserted-by":"crossref","first-page":"e380","DOI":"10.1093\/cid\/ciae314","article-title":"STI\/HIV testing, STIs, and HIV PrEP use among men who have sex with men (MSM) and men who have sex with men and women (MSMW) in United States, 2019-2022","volume":"82","author":"Tao","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026081803365210300_ofag483-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually transmitted infections treatment guidelines, 2021","volume":"70","author":"Workowski","year":"2021","journal-title":"MMWR Recomm Rep"},{"key":"2026081803365210300_ofag483-B3","doi-asserted-by":"crossref","first-page":"1328589","DOI":"10.3389\/fmed.2024.1328589","article-title":"Sexually transmitted coinfections among at-risk HIV-positive MSM: implications for optimal preemptive treatment","volume":"11","author":"Wu","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"2026081803365210300_ofag483-B4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0140-6736(23)01665-3","article-title":"Syphilis rates soar in the USA amid penicillin shortage","volume":"402","author":"Nelson","year":"2023","journal-title":"Lancet"},{"key":"2026081803365210300_ofag483-B5","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1056\/NEJM198505093121905","article-title":"Penicillin allergy and desensitization in serious infections during pregnancy","volume":"312","author":"Wendel","year":"1985","journal-title":"N Engl J Med"},{"key":"2026081803365210300_ofag483-B6","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1056\/NEJMc2314441","article-title":"Near-universal resistance to macrolides of Treponema pallidum in North America","volume":"390","author":"Lieberman","year":"2024","journal-title":"N Engl J Med"},{"key":"2026081803365210300_ofag483-B7","first-page":"112","article-title":"Pharmacokinetics of ceftriaxone after intravenous infusion and intramuscular injection","volume":"77","author":"Scully","year":"1984","journal-title":"Am J Med"},{"key":"2026081803365210300_ofag483-B8","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1128\/AAC.27.2.192","article-title":"Single-dose pharmacokinetics of ceftriaxone in healthy Chinese adults","volume":"27","author":"Zhou","year":"1985","journal-title":"Antimicrob Agents Chemother"},{"key":"2026081803365210300_ofag483-B9","first-page":"92","article-title":"Comparative sensitivity of treponemes of syphilis, yaws, and bejel to penicillin in vitro, with observations on factors affecting its treponemicidal action","volume":"38","author":"Nell","year":"1954","journal-title":"Am J Syph Gonorrhea Vener 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penicillin G for treatment of early syphilis in adults (trep-AB study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial","volume":"24","author":"Ubals","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"2026081803365210300_ofag483-B22","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1056\/NEJMoa044284","article-title":"Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis","volume":"353","author":"Riedner","year":"2005","journal-title":"N Engl J Med"},{"key":"2026081803365210300_ofag483-B23","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/cid\/ciab187","article-title":"Clinical efficacy of cefixime for the treatment of early syphilis","volume":"73","author":"Stafylis","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2026081803365210300_ofag483-B24","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/jac\/dkv379","article-title":"Comparison of serological responses to single-dose azithromycin (2 g) versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients in an area of low prevalence of macrolide-resistant Treponema pallidum infection","volume":"71","author":"Yang","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2026081803365210300_ofag483-B25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0109813","article-title":"Comparison of serological response to doxycycline versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients: a multi-center observational study","volume":"9","author":"Tsai","year":"2014","journal-title":"PLoS One"},{"key":"2026081803365210300_ofag483-B26","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s40121-021-00450-6","article-title":"Comparisons of serologic responses of early syphilis to treatment with a single-dose benzathine penicillin G between HIV-positive and HIV-negative 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The experience of three decades","volume":"47 Suppl","author":"Idsoe","year":"1972","journal-title":"Bull World Health Organ"},{"key":"2026081803365210300_ofag483-B29","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/jcph.2454","article-title":"Pharmacokinetics and safety of intramuscular injectable benzathine penicillin G in Japanese healthy participants","volume":"64","author":"Li","year":"2024","journal-title":"J Clin Pharmacol"},{"key":"2026081803365210300_ofag483-B30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1084\/jem.85.4.423","article-title":"Relation of the size of the inoculum and the age of the infection to the curative dose of penicillin in experimental syphilis, with particular reference to the feasibility of its prophylactic use","volume":"85","author":"Eagle","year":"1947","journal-title":"J Exp Med"},{"key":"2026081803365210300_ofag483-B31","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1056\/NEJM199204163261606","article-title":"Acquired syphilis in adults","volume":"326","author":"Hook","year":"1992","journal-title":"N Engl J Med"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofag483\/70558280\/ofag483.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/13\/8\/ofag483\/70558280\/ofag483.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/13\/8\/ofag483\/70558280\/ofag483.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:37:04Z","timestamp":1787038624000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofag483\/8756933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofag483","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8,1]]},"article-number":"ofag483"}}