{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:15:12Z","timestamp":1790882112008,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N41A640208"],"award-info":[{"award-number":["N41A640208"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"crossref","award":["HSRI 63-106"],"award-info":[{"award-number":["HSRI 63-106"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"crossref","award":["63-020"],"award-info":[{"award-number":["63-020"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"crossref","award":["65-030"],"award-info":[{"award-number":["65-030"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Dolutegravir (DTG) is recommended as first-line treatment for Thai people living with HIV (PLWH). Real-world studies show high plasma concentration variability, which may increase neuropsychiatric adverse effects. This variability can be influenced by both genetic and nongenetic factors, but data for the Thai population are insufficient. We investigated factors associated with DTG pharmacokinetics in Thai PLWH. Methods: A cross-sectional analysis was conducted in Thai PLWH receiving a 50 mg DTG-based regimen. Intensive blood sampling was performed to determine DTG pharmacokinetic parameters using a non-compartmental analysis. Genotyping for UGT1A1, ABCG2, and NR1I2 was performed. Univariable and multivariable linear regression analyses were used to identify factors associated with DTG pharmacokinetics. Results: A total of 104 Thai PLWH were included. Multivariable analysis demonstrated that both the UGT1A1 poor metabolizer phenotype and body weight were independently associated with DTG exposure. After adjusting for body weight, the UGT1A1 poor metabolizer phenotype was associated with increases of 5.18% in AUC0\u201324 and 20.59% in Ctrough. No significant association was found between the ABCG2 421 C&gt;A polymorphism and DTG pharmacokinetic parameters. Conclusions: Body weight and the UGT1A1 poor metabolizer phenotype significantly impacted DTG exposure in Thai PLWH. Those with the UGT1A1 poor metabolizer, particularly with lower body weight, had significantly increased DTG exposures. These findings highlight that dose optimization may be worth exploring in selected individuals in this population.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111499","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T09:44:53Z","timestamp":1763631893000},"page":"1499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Association Between Genetic Polymorphisms of UGT1A1, ABCG2, and NR1I2 and Dolutegravir Pharmacokinetic Parameters in Thai People Living with HIV"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9923-5779","authenticated-orcid":false,"given":"Anan","family":"Chanruang","sequence":"first","affiliation":[{"name":"PhD Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-4906","authenticated-orcid":false,"given":"Angela K.","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1508-2358","authenticated-orcid":false,"given":"Sasithorn","family":"Sirilun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7258-5086","authenticated-orcid":false,"given":"Suthunya","family":"Chupradit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-1408","authenticated-orcid":false,"given":"Sasiwimol","family":"Ubolyam","sequence":"additional","affiliation":[{"name":"The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research and Infectious Diseases Centre, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4292-1797","authenticated-orcid":false,"given":"Napon","family":"Hiranburana","sequence":"additional","affiliation":[{"name":"The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research and Infectious Diseases Centre, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-1123","authenticated-orcid":false,"given":"Yong Soon","family":"Cho","sequence":"additional","affiliation":[{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-850X","authenticated-orcid":false,"given":"Jae Gook","family":"Shin","sequence":"additional","affiliation":[{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-9611","authenticated-orcid":false,"given":"Anchalee","family":"Avihingsanon","sequence":"additional","affiliation":[{"name":"The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research and Infectious Diseases Centre, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-2462","authenticated-orcid":false,"given":"Baralee","family":"Punyawudho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2019). Update of Recommendation on First- and Second-Line Antiretroviral Regimens, WHO."},{"key":"ref_2","unstructured":"(2025, April 26). Thailand National Guidelines on Human Immunodeficiency Virus Infection and Acquired Immune Deficiency Syndrome (HIV\/AIDS) Diagnosis, Treatment and Prevention 2021\/2022 [Internet]. Bureau of AIDS, TB and STIs Department of Disease Control, Ministry of Public Health. Available online: https:\/\/www.thaiaidssociety.org\/wp-content\/uploads\/2022\/02\/Thailand-National-Guidelines-on-HIV-AIDS-Diagnosis-Treatment-and-Prevention-2020-2021.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s40262-013-0093-2","article-title":"Clinical Pharmacokinetic, Pharmacodynamic and Drug-Interaction Profile of the Integrase Inhibitor Dolutegravir","volume":"52","author":"Cottrell","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1473-3099(11)70290-0","article-title":"Once daily dolutegravir (S\/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: Planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial","volume":"12","author":"Maggiolo","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"ofaf135","DOI":"10.1093\/ofid\/ofaf135","article-title":"Efficacy and Safety Outcomes in Adults Initiating Dolutegravir\/Lamivudine with High Viral Load in the GEMINI-1\/-2 and STAT Trials","volume":"12","author":"Rolle","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/QAD.0000000000001459","article-title":"Neuropsychiatric adverse effects on dolutegravir: An emerging concern in Europe","volume":"31","author":"Menard","year":"2017","journal-title":"AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.eimc.2020.02.018","article-title":"Neuropsychiatric adverse effects of dolutegravir in real-life clinical practice","volume":"39","year":"2021","journal-title":"Enfermedades Infecc. Microbiol. Cl\u00ednica Engl. Ed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2174\/1574886313666180116124046","article-title":"Dolutegravir-Related Neurological Adverse Events: A Case Report of Successful Management with Therapeutic Drug Monitoring","volume":"13","author":"Francois","year":"2018","journal-title":"Curr. Drug Saf."},{"key":"ref_9","unstructured":"Solas, C., Bregigeon, S., Faucher-zaegel, O., Laraoche, H., Obry-roguet, V., Quaranta, S., Tamalet, C., Canet, B., Lacarelle, B., and Poizot-martin, I. (2017, January 14\u201317). Higher dolutegravir plasma trough concentration (Ctrough) in patients presenting side effects: Interest of therapeutic drug monitoring?. Proceedings of the International Workshop on Clinical Pharmacology of Antiviral Therapy, Chicago, IL, USA."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/jac\/dkz558","article-title":"Genetic influence of ABCG2, UGT1A1 and NR1I2 on dolutegravir plasma pharmacokinetics","volume":"75","author":"Elliot","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/bcp.12639","article-title":"Population pharmacokinetics of dolutegravir in HIV-infected treatment-naive patients","volume":"80","author":"Zhang","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1093\/jac\/dkz217","article-title":"Population pharmacokinetics of dolutegravir: Influence of drug\u2013drug interactions in a real-life setting","volume":"74","author":"Barcelo","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/14622416.2024.2441104","article-title":"Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: A systematic review","volume":"25","author":"Bevers","year":"2024","journal-title":"Pharmacogenomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0021522","DOI":"10.1128\/aac.00215-22","article-title":"Population Pharmacokinetic Model and Alternative Dosing Regimens for Dolutegravir Coadministered with Rifampicin","volume":"66","author":"Boffito","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1097\/FTD.0000000000000618","article-title":"Dolutegravir Population Pharmacokinetics in a Real-Life Cohort of People Living With HIV Infection: A Covariate Analysis","volume":"41","author":"Parant","year":"2019","journal-title":"Ther. Drug Monit."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/psp4.13244","article-title":"The population pharmacokinetics of dolutegravir co-administered with rifampicin in Thai people living with HIV: Assessment of alternative dosing regimens","volume":"14","author":"Punyawudho","year":"2025","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/infdis\/jiac174","article-title":"Pharmacogenetics of Dolutegravir Plasma Exposure Among Southern Africans With Human Immunodeficiency Virus","volume":"226","author":"Cindi","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/dmd.112.048918","article-title":"In Vitro Investigations into the Roles of Drug Transporters and Metabolizing Enzymes in the Disposition and Drug Interactions of Dolutegravir, a HIV Integrase Inhibitor","volume":"41","author":"Reese","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/cpt.269","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing","volume":"99","author":"Gammal","year":"2016","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_20","first-page":"2240","article-title":"Evaluation of the effect of UGT1A1 polymorphisms on the pharmacokinetics of oral and long-acting injectable cabotegravir","volume":"75","author":"Patel","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/clpt.2009.12","article-title":"Pharmacokinetics of Raltegravir in Individuals With UGT1A1 Polymorphisms","volume":"85","author":"Wenning","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.jiac.2015.06.008","article-title":"Correlation between UGT1A1 polymorphisms and raltegravir plasma trough concentrations in Japanese HIV-1-infected patients","volume":"21","author":"Yagura","year":"2015","journal-title":"J. Infect. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yagura, H., Watanabe, D., Kushida, H., Tomishima, K., Togami, H., Hirano, A., Takahashi, M., Hirota, K., Ikuma, M., and Kasai, D. (2017). Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2717-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/FPC.0000000000000308","article-title":"High plasma concentrations of dolutegravir in patients with ABCG2 genetic variants","volume":"27","author":"Tsuchiya","year":"2017","journal-title":"Pharmacogenet. Genom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.24875\/AIDSRev.19000023","article-title":"Neuropsychiatric Adverse Events with Dolutegravir and Other Integrase Strand Transfer Inhibitors","volume":"21","author":"Hoffmann","year":"2019","journal-title":"AIDS Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Patel, D.A., Snedecor, S.J., Tang, W.Y., Sudharshan, L., Lim, J.W., Cuffe, R., Pulgar, S., Gilchrist, K.A., Camejo, R.R., and Stephens, J. (2014). 48-Week Efficacy and Safety of Dolutegravir Relative to Commonly Used Third Agents in Treatment-Naive HIV-1\u2013Infected Patients: A Systematic Review and Network Meta-Analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105653"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1097\/QAD.0000000000001351","article-title":"Discontinuation of treatment and adverse events in an Italian cohort of patients on dolutegravir","volume":"31","author":"Bonfanti","year":"2017","journal-title":"AIDS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2217\/pgs.13.190","article-title":"Evaluation of the Effect of UGT1A1 Polymorphisms on Dolutegravir Pharmacokinetics","volume":"15","author":"Chen","year":"2014","journal-title":"Pharmacogenomics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Atasilp, C., Kanjanapipak, J., Vichayaprasertkul, J., Jinda, P., Tiyasirichokchai, R., Srisawasdi, P., Prempunpong, C., Chamnanphon, M., Puangpetch, A., and Vanwong, N. (2022). Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population. BMC Pediatr., 22.","DOI":"10.1186\/s12887-022-03311-4"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/00008571-200212000-00006","article-title":"Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups","volume":"12","author":"Innocenti","year":"2002","journal-title":"Pharmacogenetics Genom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/jcph.70061","article-title":"Clinical Evaluation of Drug\u2013Drug Interactions Between Bictegravir and Strong Inhibitors\/Inducers of the CYP3A4, UGT1A1, or P-gp Pathways","volume":"65","author":"Arora","year":"2025","journal-title":"J. Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/QAI.0000000000003358","article-title":"Impact of Genetic Variants in ABCG2, NR1I2, and UGT1A1 on the Pharmacokinetics of Dolutegravir in Children","volume":"95","author":"Spector","year":"2024","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/jpet.119.264424","article-title":"ABCG2 Deficiency Does Not Alter Dolutegravir Metabolism and Pharmacokinetics","volume":"374","author":"Zhu","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1499\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:18:01Z","timestamp":1763788681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["pharmaceutics17111499"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17111499","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}