{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:03Z","timestamp":1792510743977,"version":"4.5.0"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project","award":["2025ZD01905305"],"award-info":[{"award-number":["2025ZD01905305"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      HIV infection remains a critical global public health concern. A potential long-acting therapeutic agent, 4\u2032-ethynyl-2-fluoroadenosine analog 1c (CL-197), was investigated in a first-in-human phase 1 clinical trial. This single-center, randomized, double-blind, dose-escalation, placebo-controlled study assessed the safety and pharmacokinetics (PKs) of five doses of CL-197 (1, 10, 30, 60, and 100 mg) in healthy adults aged 18\u201345 years. The 1 mg group was open-label (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 4), while the other groups were randomized 4:1 to CL-197 or placebo. The primary endpoints were safety and tolerability. The PK evaluation involved the characterization of systemic exposure parameters (based on plasma drug concentrations and peripheral blood mononuclear cell [PBMC] drug concentrations) and urinary excretion parameters. CL-197 was well tolerated at all dose levels. The most frequently reported adverse reactions were sinus arrhythmia, followed by decreased apolipoprotein B, decreased blood iron, increased triglycerides, and elevated low-density lipoprotein. Plasma PKs showed dose-proportional exposure, with a mean time to maximum plasma concentration (\n                      <jats:italic toggle=\"yes\">T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) of 0.50\u20131.00 h. As the dose increased, the elimination time was prolonged. The plasma drug concentrations were approximately dose-proportional, whereas\n                      <jats:italic toggle=\"yes\">AUC<\/jats:italic>\n                      <jats:sub>0-t<\/jats:sub>\n                      and\n                      <jats:italic toggle=\"yes\">AUC<\/jats:italic>\n                      <jats:sub>0-\u221e<\/jats:sub>\n                      exhibited non-linear characteristics within the range of 1-100mg, with the mean elimination half-life (\n                      <jats:italic toggle=\"yes\">t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      ) increasing from 1.39 to 10.20 h across doses. The mean\n                      <jats:italic toggle=\"yes\">t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      in PBMCs was 61.29 h and 43.80 h in the 30 mg and 60 mg dose groups, respectively, and the median\n                      <jats:italic toggle=\"yes\">T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      was 12 h. In conclusion, a single administration of CL-197 demonstrated an acceptable safety profile in younger adults. The intracellular CL-197-TP in PBMCs had a long half-life, providing preliminary support for the potential use of extended dosing intervals in further development.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>\n                        <jats:bold>CLINICAL TRIALS<\/jats:bold>\n                      <\/jats:title>\n                      <jats:p>\n                        This study is registered with ClinicalTrials.gov as\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05944848\" xlink:type=\"simple\">NCT05944848<\/jats:ext-link>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00984-26","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:01:24Z","timestamp":1788534084000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Safety and pharmacokinetics of CL-197, a potent compound with low cytotoxicity against HIV-1: a randomized, double-blind, placebo-controlled, first-in-human phase 1 clinical trial"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-8422","authenticated-orcid":true,"given":"Yuming","family":"Guo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/01vjw4z39","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Traditional Chinese Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5724-3464","authenticated-orcid":false,"given":"Yonggang","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Bi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyun","family":"Gou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037cjxp13","id-type":"ROR","asserted-by":"publisher"}],"name":"China-Japan Friendship Hospital","place":["Beijing, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfa","family":"Du","sequence":"additional","affiliation":[{"name":"Henan Genuine Biotech Co., Ltd.","place":["Pingdingshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4350-8494","authenticated-orcid":false,"given":"Yi","family":"Ou","sequence":"additional","affiliation":[{"name":"Henan Genuine Biotech Co., Ltd.","place":["Pingdingshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8119-7146","authenticated-orcid":false,"given":"Na","family":"Guo","sequence":"additional","affiliation":[{"name":"Henan Genuine Biotech Co., Ltd.","place":["Pingdingshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-6685","authenticated-orcid":false,"given":"Fu-Sheng","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gw3ra78","id-type":"ROR","asserted-by":"publisher"}],"name":"Senior 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HIV statistics\uff0cglobally and by WHO region\uff0c2025\uff3bEB\/ OL]. Available from: https:\/\/cdn.who.int\/media\/docs\/default-source\/hq-hiv-hepatitis-and-stis-library\/who-ias-hiv-statistics_2025-new.pdf. Retrieved 14 Jul 2025."},{"key":"e_1_3_5_3_2","unstructured":"UNAIDS. 2026. Global HIV & AIDS statistics--fact sheet. Available from: https:\/\/www.unaids.org\/en\/resources\/fact-sheet. Retrieved 27 July 2026."},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/ID9.0000000000000176"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.10.004"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12236"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002623"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit529"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4010"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr5002035"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3231"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1359-6446(00)01558-0"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00697"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4ob01449a"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/v15020544"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00761"},{"key":"e_1_3_5_17_2","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents Department of Health and Human Services. 2025. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Available from: https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/adult-adolescent-arv\/guidelines-adult-adolescent-arv.pdf. Retrieved 17 Oct 2025."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.24543"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.13542"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1711460"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2115542"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00984-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00984-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:49:19Z","timestamp":1792507759000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00984-26"}},"subtitle":[],"editor":[{"given":"Zhaohui","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":21,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1128\/aac.00984-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00984-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00984-26"}}