• Bernard Surial, Catrina Mugglin, Alexandra Calmy, Matthias Cavassini, Huldrych F Günthard, Marcel Stöckle, Enos Bernasconi, Patrick Schmid, Philip E Tarr, Hansjakob Furrer, Bruno Ledergerber, Gilles Wandeler, Andri Rauch, and Swiss HIV Cohort Study.
• Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (B.S., C.M., H.F., G.W., A.R.).
• Ann. Intern. Med. 2021 Jun 1; 174 (6): 758-767.

BackgroundTenofovir-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.ObjectiveTo assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.DesignCohort study.Setting5 university hospitals, affiliated hospitals, and private physicians in Switzerland.Participants4375 adults living with HIV who received TDF-containing ART for 6 months or longer.MeasurementsChanges 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.Results4375 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.LimitationShort follow-up, small subgroup analyses, and potential residual confounding.ConclusionReplacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.Primary Funding SourceSwiss National Science Foundation.

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