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However, long-term comparative data using robust statistical methods in real-world settings\u2014especially among antiretroviral therapy (ART)-naive people living with HIV (PLWH)\u2014are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study compared the long-term metabolic and safety profiles of TDF versus TAF in ART-naive PLWH, using mixed-effects modeling to inform clinical decisions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicenter retrospective cohort study was conducted across 10 HIV centers in T\u00fcrkiye from 2018 to 2022. The study included 540 ART-naive PLWH aged\u2009\u2265\u200918 years, treated with TDF- or TAF-based regimens for \u2265\u200912 months, with \u2265\u200924 months follow-up. Primary endpoints were changes in renal function (eGFR), bone mineral density (T-scores), and lipid profiles over 48 months. Mixed-effects regression models adjusted for baseline demographics, comorbidities, and concomitant medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both TAF (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009197) and TDF (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009343) showed similar virological suppression and CD4\u2009+\u2009recovery, with no significant differences in HIV RNA (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.24) or CD4\u2009+\u2009counts (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.54). At 24 months, TAF led to greater increases in total cholesterol, non-HDL cholesterol, LDL cholesterol, and triglycerides (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.039), though differences were not significant at 48 months. Phosphorus levels were similar (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.2), but eGFR declined more with TAF at 48 months (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Overall changes in bone mineral density were comparable (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.18). GGT increases at 24 months were greater with TAF in both sexes; the clinical significance is uncertain and warrants monitoring.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Over 48 months, TAF and TDF achieved equivalent virological and immunological responses. In this real-world retrospective cohort, TAF was linked to short-term lipid increases and a greater eGFR decline, while bone density changes were similar overall. Given baseline imbalances, unmeasured confounding (including concomitant medications and regimen components), and multiple testing, these findings should be interpreted cautiously and considered hypothesis-generating. Antiretroviral choice should be individualized.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-025-01003-0","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T15:35:59Z","timestamp":1760456159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-term metabolic and safety profiles of tenofovir alafenamide and tenofovir disoproxil fumarate in ART-naive people living with HIV: a multicenter retrospective study using a mixed-effects model"],"prefix":"10.1186","volume":"26","author":[{"given":"Oguz","family":"Karabay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli","family":"Vatan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Ucar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilknur","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurselin Can","family":"Balta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Kanturk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridvan","family":"Dumlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Cag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hulya","family":"Caskurlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve Tokgoz","family":"\u015eik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahide Asik","family":"Otman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umay","family":"Balci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seniha","family":"Senbayrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sila","family":"Akhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muge Toygar","family":"Deniz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Yekenkurul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevin","family":"Ince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekir","family":"Tunca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba Damar","family":"Cakirca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliye","family":"Bastug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unal","family":"Erkorkmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertugrul","family":"Guclu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"1003_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s40121-018-0201-6","volume":"7","author":"A Chawla","year":"2018","unstructured":"Chawla A, Wang C, Patton C, Murray M, Punekar Y, de Ruiter A, et al. 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The application was thoroughly reviewed, and the committee determined that the study adhered to ethical standards and posed no scientific concerns. The ethical approval was granted on January 31, 2023, under the reference number E-71522473-050.01.04-216291-46. Although this retrospective cohort study was not registered on a clinical trials platform due to its observational nature, it adhered to ethical guidelines and was approved by the institutional review board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"This study was designed as a retrospective study, and therefore, informed consent was not obtained. The study was conducted using previously collected data, and ethical approval was obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"164"}}