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We investigated determinants of early changes in serum creatinine in a southern African cohort starting first\u2010line dolutegravir\u2010based antiretroviral therapy (ART).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV\u20101 RNA concentration, CD4 T\u2010cell count, total body weight and co\u2010trimoxazole use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9)\u00a0\u03bcmol.L<jats:sup>\u22121<\/jats:sup>. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24\u2010h concentration\u2013time curve (change in creatinine coefficient [<jats:italic>\u03b2<\/jats:italic>]\u2009=\u20092.78\u2009\u03bcmol.L<jats:sup>\u22121<\/jats:sup> [95% confidence interval (CI) 0.54, 5.01]), TDF use (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20092.30 [0.53, 4.06]), male sex (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20095.20 [2.92, 7.48]), baseline serum creatinine (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.22 [\u22120.31, \u22120.12]) and <jats:italic>UGT1A1<\/jats:italic> rs929596 A\u2192G polymorphism with a dominant model (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22122.33 [\u22124.49, \u22120.17]). The latter did not withstand correction for multiple testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir\u2010based ART. <jats:italic>UGT1A1<\/jats:italic> polymorphisms may play a role, but further research on genetic determinants is needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16009","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T04:20:02Z","timestamp":1707452402000},"page":"1247-1257","source":"Crossref","is-referenced-by-count":10,"title":["Determinants of early change in serum creatinine after initiation of dolutegravir\u2010based antiretroviral therapy in South Africa"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-5879","authenticated-orcid":false,"given":"Rephaim","family":"Mpofu","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-0178","authenticated-orcid":false,"given":"Aida N.","family":"Kawuma","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-8150","authenticated-orcid":false,"given":"Roeland E.","family":"Wasmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South 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