Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV

Surial, Bernard; Mugglin, Catrina; Calmy, Alexandra; Cavassini, Matthias; Günthard, Huldrych F.; Stöckle, Marcel; Bernasconi, Enos; Schmid, Patrick; Tarr, Philip E.; Furrer, Hansjakob; Ledergerber, Bruno; Wandeler, Gilles; Rauch, Andri

doi:10.7326/m20-4853

Cited by 82 publications

(85 citation statements)

References 24 publications

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“…While the mechanism by which TDF might protect from development or progression of steatosis have to be further investigated to exclude a solely effect of weight suppression, the beforehand reported weight suppressive effect of TDF is supported by our results, since patients under TDF were protected against clinically significant weight gain of more than 5% or 10%, respectively. Further support comes from ART studies which also highlight the weight suppressive effect of TDF which is unmasked or reverted after switching from TDF to TAF [36] . In fact, Mayer et al.…”

Section: Discussionmentioning

confidence: 99%

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)

Bischoff

Schwarze‐Zander

et al. 2021

EClinicalMedicine

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Background De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD. Methods This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates. Findings 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m 2 (OR: 4·238, 95% CI: 2·078–8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362–10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370–4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315–24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12–0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101–0·945; p = 0·04). Interpretation Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m 2 . While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis. Funding There was no additional funding received for this project. All funders mentioned in the ‘declaration of interests’ section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Section: Discussionmentioning

confidence: 99%

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)

Bischoff

Schwarze‐Zander

et al. 2021

EClinicalMedicine

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“…Body weight changed after switching from TDF to TAF in two retrospective studies in HIV-positive patients in 2019 ( Schafer et al, 2019 ; Gomez et al, 2019 ). Two large cohort studies showed a mean weight increase of 1.7 kg at 18 months after switching to TAF in Switzerland ( Surial et al, 2021 ) and early and pronounced weight gain (1.80 to 4.47 kg/year) in the United States ( Mallon et al, 2021 ). Recently, a similar finding was found in patients with CHB.…”

Section: Discussionmentioning

confidence: 99%

“…Second, we did not measure the serum lipid profiles, fasting glucose and hemoglobin A1c. Some studies showed worsening lipid levels in PLWH after switching to TAF, and the total cholesterol, low-density lipoprotein, and high-density lipoprotein were higher in TAF monotherapy than in TDF monotherapy ( Surial et al, 2021 ; Byun et al, 2021 ). Additionally, comorbidities, such as diabetes, cardiovascular disease, and malignancy were not adjusted with renal function or weight.…”

Section: Discussionmentioning

confidence: 99%

“…Two double-blind studies showed that TAF had a high viral suppression rate and less severe bone and renal side effects ( Buti et al, 2016 ; Chan et al, 2016 ). Recent studies have shown weight increases after switching from TDF to TAF in people living with human immunodeficiency virus (HIV; PLWH) ( Schafer et al, 2019 ; Surial et al, 2021 ). However, only few studies are available about the real-world data on switching from TDF to TAF in patients with CHB.…”

Section: Introductionmentioning

confidence: 99%

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Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study

Hsu

et al. 2021

PeerJ

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Background Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited. Methods This retrospective study included 167 nucleos(t)ide analogue (NA)-naive patients with CHB. All the patients received TDF at least 12 months before switching and TAF at least 12 months after switching at a single medical center. The Friedman test with Dunn–Bonferroni post hoc tests and repeated-measures analysis of variance was used to analyze the effect of complete viral suppression, alanine aminotransferase (ALT) level normalization, renal function changes, body weight, and body mass index in the periods before and after switching. Results The mean age and TDF treatment duration were 52 ± 11 years and 2.8 years (interquartile range, 1.51–5.15 years), respectively. The complete viral suppression rate was similar between the time of switching and 48 weeks after switching to TAF (77.8% vs 76%, P = 1.000). The percentage of alanine aminotransferase (ALT) normalization increased from 26.3% at TDF start to 81.4% (P < 0.001) at time of switching and 89.2% at 48 weeks after switching to TAF (P = 0.428). The median estimated glomerular filtration rate decreased from 100.09 mL/min/1.73 m² at TDF start to 91.97 mL/min/1.73 m² (P < 0.001) at the time of switching and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73m², P = 1.000). The body weight decreased from 69.2 ± 12.2 kg at TDF start to 67.4 ± 12.1 kg (P < 0.001) at the time of switching to TAF and returned to 68.7 ± 12.7 kg (P < 0.001) 48 weeks thereafter. The body mass index (BMI) decreased from 25 ± 3.3 kg/m² at TDF start to 24.5 ± 3.3 kg/m² (P = 0.002) at the time of switching to TAF and returned to 25.1 ± 3.6 kg/m² (P < 0.001) 48 weeks thereafter. Conclusions Our study showed that switching to TAF from TDF had good antiviral effectiveness and stabilized renal function. The body weight and BMI decreased during TDF therapy and regained after switching to TAF.

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“…Risks and benefits of switching from TDF to TAF must be weighed prior to switch. Risks to the kidney and bones with TDF (e.g., renal tubular dysfunction, bone mineral density) [2,3] must be balanced against cardiovascular risks with TAF (e.g., dyslipidemia, weight gain) [32,[34][35][36]. The patient's history, comorbidities and other risk factors must therefore be considered in the decision-making process, and regular screening may be advised.…”

Section: Discussionmentioning

confidence: 99%

Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization

Brunet¹,

Mallon

Fusco³

et al. 2021

Clin Drug Investig

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Background and Objective Many people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice. Methods PLWH prescribed TDF for ≥ 4 weeks who switched to TAF were identified in the OPERA cohort. Patterns of dyslipidemia were compared before and after switch based on NCEP ATPIII guidelines. Elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD ≥ 7.5%) and statin use were assessed. Results Among 6423 PLWH switched from TDF to TAF, the proportion with dyslipidemia/severe dyslipidemia observed after switch from TDF to TAF increased statistically significantly (p < 0.0001) with total cholesterol (5-10%), low-density lipoprotein cholesterol (16-23%), and triglycerides (21-27%), but decreased statistically significantly with high-density lipoprotein cholesterol (35-30%, p < 0.0001). These patterns of dyslipidemia persisted in sensitivity analyses restricted to PLWH who maintained all other antiretrovirals (N = 4328) or stratified by pharmaco-enhancer use before and after switch. An elevated ASCVD risk was detected in 29% before and 31% after switch. As many as 59% of PLWH with an elevated ASCVD risk were not prescribed a statin after switch from TDF to TAF. Conclusions In this large, diverse population of PLWH in the USA, the switch from TDF to TAF was associated with development of less favorable lipid profiles, regardless of pharmaco-enhancers or third-agent use. Statins remained underutilized after a switch from TDF to TAF.

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Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV

Cited by 82 publications

References 24 publications

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)

Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study

Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization

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