Bernard Surial1, Catrina Mugglin1, Alexandra Calmy2, Matthias Cavassini3, Huldrych F Günthard4, Marcel Stöckle5, Enos Bernasconi6, Patrick Schmid7, Philip E Tarr8, Hansjakob Furrer1, Bruno Ledergerber4, Gilles Wandeler1, Andri Rauch1. 1. Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (B.S., C.M., H.F., G.W., A.R.). 2. Geneva University Hospital, University of Geneva, Geneva, Switzerland (A.C.). 3. University Hospital of Lausanne, University of Lausanne, Lausanne, Switzerland (M.C.). 4. University Hospital Zurich, University of Zurich, Zurich, Switzerland (H.F.G., B.L.). 5. University Hospital Basel, University of Basel, Basel, Switzerland (M.S.). 6. Regional Hospital of Lugano, University of Geneva, and University of Southern Switzerland, Lugano, Switzerland (E.B.). 7. Cantonal Hospital of St. Gallen, St. Gallen, Switzerland (P.S.). 8. and Kantonsspital Baselland, University of Basel, Basel, Switzerland (P.E.T.).
Abstract
BACKGROUND: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. OBJECTIVE: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. DESIGN: Cohort study. SETTING: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. PARTICIPANTS: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. MEASUREMENTS: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests. RESULTS: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months. LIMITATION: Short follow-up, small subgroup analyses, and potential residual confounding. CONCLUSION: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels. PRIMARY FUNDING SOURCE: Swiss National Science Foundation.
BACKGROUND:Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. OBJECTIVE: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. DESIGN: Cohort study. SETTING: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. PARTICIPANTS: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. MEASUREMENTS: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obeseparticipants were calculated using 2-proportions Z tests. RESULTS: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months. LIMITATION: Short follow-up, small subgroup analyses, and potential residual confounding. CONCLUSION: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels. PRIMARY FUNDING SOURCE: Swiss National Science Foundation.
Authors: Mohammed Siddiqui; T J Moore; Dustin M Long; Greer A Burkholder; Amanda Willig; Christina Wyatt; Sonya Heath; Paul Muntner; Edgar Turner Overton Journal: AIDS Res Hum Retroviruses Date: 2022-08-23 Impact factor: 1.723
Authors: Maurice Michel; Alisha Wahl; Malena Anders; Saleh A Alqahtani; Wolfgang M Kremer; Peter R Galle; Christian Labenz; Daniel Grimm; Martin Sprinzl; Jörn M Schattenberg Journal: Qual Life Res Date: 2022-08-22 Impact factor: 3.440
Authors: Emma M Kileel; Janet Lo; Carlos Malvestutto; Kathleen V Fitch; Markella V Zanni; Carl J Fichtenbaum; Edgar T Overton; Nwora Lance Okeke; Princy Kumar; Esau Joao; Judith A Aberg; Esteban Martinez; Judith S Currier; Pamela S Douglas; Heather J Ribaudo; Steven K Grinspoon Journal: Open Forum Infect Dis Date: 2021-11-20 Impact factor: 4.423
Authors: Laurence Brunet; Patrick Mallon; Jennifer S Fusco; Michael B Wohlfeiler; Girish Prajapati; Andrew Beyer; Gregory P Fusco Journal: Clin Drug Investig Date: 2021-09-21 Impact factor: 2.859