Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients

Lagoutte-Renosi, Jennifer; Flammang, Mylène; Chirouze, Catherine; Beck‐Wirth, Geneviève; Bozon, F.; Brunel, Anne-Sophie; Drobacheff-Thiebaut, Marie-Christine; Foltzer, A; Hustache‐Mathieu, Laurent; Kowalczyk, Jakub; Michel, Catherine; Davani, Siamak; Muret, Patrice

doi:10.2174/1570162x18666200824101838

Cited by 11 publications

(9 citation statements)

References 19 publications

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“…Consistent with these previous reports, in our study, cholesterol levels decreased significantly during TDF administration ( Fig 2B ). However, other reports have shown that switching from TDF to TAF increased levels of cholesterols, including T-chol, LDL-c, and HDL-c, in patients with HIV infection [ 16 , 30 , 31 ]. As HDL-c and LDL-c have opposite effects on the development of atherosclerosis, the effects of changing both serum parameters are not clear.…”

Section: Discussionmentioning

confidence: 99%

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B

Suzuki

Suda²,

Yamamoto³

et al. 2022

PLoS ONE

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For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6–12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.

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Section: Discussionmentioning

confidence: 99%

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B

Suzuki

Suda²,

Yamamoto³

et al. 2022

PLoS ONE

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“…These results enlighten the potential role of inflammation/oxidative stress as drivers for dyslipidemia, in addition to ART and individual factors. The different effect on lipids of TAF vs TDF, previously identified in clinical trials, was confirmed in the real life setting in several studies: switching TDF to TAF increased TC, LDL-C, HDL-C and TG while the LDL-C/HDL-C ratio remained stable (44,45). When TAF was switched back to TDF, lipid levels returned to previous values (46).…”

Section: -2 Mechanismsmentioning

confidence: 63%

Recent data on adipose tissue, insulin resistance, diabetes and dyslipidaemia in antiretroviral therapy controlled HIV-infected persons

Capeau

Lagathu

Béréziat

et al. 2021

Current Opinion in HIV and AIDS

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Purpose of review: Increased total body fat with truncal redistribution is common in antiretroviral-treatment(ART)-controlled persons living with-HIV(PLWH), leading to insulin resistance, prediabetes/diabetes and dyslipidemia. We address these topics here.Recent findings: Most antiretrovirals are associated with gain in trunk fat, including visceral adipose tissue(VAT). Protease-inhibitors(PI) could inhibit white fat ability to dissipate energy (i.e. beiging) favoring fat gain. Expansion of VAT is associated with a pro-inflammatory profile linked to the tryptophan-kynurenine pathway and CD4 subtypes. ART-associated increased AT quantity leads to decreased AT density, insulin resistance and dyslipidemia that could be improved by lifestyle modifications.PLWH present high level of insulin resistance, regardless of their treatment, and a higher prevalence of prediabetes, but not diabetes, than non-infected persons. Otherwise, HbA1c values appear inaccurate to diagnose prediabetes/diabetes in PLWH.ART-related-dyslipidemia is characterized by elevated LDL-C and/or high triglycerides and reduced HDL-C. Whereas treatment with PIs generally results in worsened lipid values, treatment with integrase-strand-transfer-inhibitors is associated with a better profile.Tenofovir-alafenamide is associated with higher lipid levels than tenofovir-disoproxilfumarate. Treatment of LDL-C-dyslipidemia could benefit, in statin-insufficiently controlled patients, from the class of proprotein-convertase-subtilsin-kenin-type-9(PCSK-9) inhibitors.

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“…Even though newer antiretrovirals do not elevate circulating lipids to the same extent, tenofovir prodrugs, including tenofovir alafenamide, increase cholesterol species (91). This occurs despite the known impact of HIV on diminishing total cholesterol levels (86,(92)(93)(94)(95). Conversely other ARTs, including raltegravir, dolutegravir, and bictegravir, have either a beneficial or minimal impact on the cholesterol profile (which was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

White

Gausepohl

Seneviratne

et al. 2022

Preprint

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Human immunodeficiency virus infection (HIV) continues to promote neurocognitive impairment, mood disorders, and brain atrophy even in the modern era of viral suppression. Brain lipids are vulnerable to HIV-associated energetic strain and contribute to HIV-associated neurologic dysfunction due to alterations in lipid breakdown and structural lipid composition. HIV neuropathology is region dependent, yet there has not been a comprehensive spatial evaluation of brain lipids during infection that may impact neurologic function. To address this gap, we evaluated brain lipid distribution using matrix laser desorption/ionization imaging mass spectrometry (MALDI-IMS) across four brain regions (parietal cortex, midbrain, thalamus, and temporal cortex), as well as kidney for a peripheral tissue control, in a virally suppressed simian immunodeficiency virus (SIV)-infected rhesus macaque. We assessed lipids indicative of fat breakdown (acylcarnitines) and critical structural lipids (phosphatidylcholines and phosphatidylethanolamines) across fatty acid chain lengths and degrees of unsaturation. Acylcarnitines with very long-chain, polyunsaturated fatty acids were more abundant across all brain regions than shorter chain, saturated or monounsaturated species. We observed two distinct brain lipid distribution patterns for acylcarnitines and phosphatidylcholines. However, no clear expression patterns emerged for phosphatidylethanolamines. Surprisingly, acylcarnitines were largely missing in kidney, while common phosphatidylcholines and phosphatidylethanolamines were absent in kidney. Overall, our study provides substantial evidence for persistent bioenergetic changes to the brain despite viral suppression, including region-dependent mobilization of acylcarnitines for oxidation and disparities in the presence of key phospholipids necessary for maintaining proper brain structure and function. These data indicate that region-specific interventions to restore proper lipid metabolism are essential for treating HIV neurologic disease in the era of ART.

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Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients

Cited by 11 publications

References 19 publications

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B

Recent data on adipose tissue, insulin resistance, diabetes and dyslipidaemia in antiretroviral therapy controlled HIV-infected persons

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

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