<p>The Effect of Switching from Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) on Liver Enzymes, Glucose, and Lipid Profile</p>

Abstract

Objective We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile. Methods Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t -test and signed rank test. Results A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A–B, 93.7% with undetectable HIV-viral load. Mean age was 46.7±10.7 years, body mass index was 25.0±3.9 kg/m 2 , median CD4 cell count was 634 cell/µL (interquartile range [IQR]=439–900), aspartate aminotransferase (AST) was 23 (IQR=19–30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17–34) IU/L. At T1, both AST (median=−1, IQR=−5–2 IU/L, P =0.004) and ALT (median=−2, IQR=−7–3 IU/L, P =0.0004) showed a significant decrease. Among 28 patients with ALT >40 at baseline, reduction was significant both clinically (−17, IQR=−32–−1) and statistically ( P =0.0003). Total cholesterol levels (TC) increased (+13.4±3.8 mg/dL, P =0.0006), as well as HDL-cholesterol (HDL-C) (+3.8±1.2 mg/dL, P =0.02), LDL Cholesterol (LDL-C) (+7.6±3.4, P =0.03) and glucose (+4.0±1.8 mg/dL, P =0.02). D:A:D: and Framingham risk score did not change at 6 months after switch. Conclusion A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT >40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.

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

“…The magnitude of lipid increases observed in this study (CHOL: + 7.9%, LDL: + 11.1%, HDL: + 7.1%, TG: + 23.8%) was consistent with the results of a smaller observational study of 238 PLWH switching from TDF to TAF, which reported statistically significant relative increases in CHOL, LDL and HDL of a similar magnitude to those reported here [ 19 – 22 ]. However, other observational studies reported larger statistically significantly increases in lipids for up to 6 months after switch [ 18 ].…”

“…ASCVD atherosclerotic cardiovascular disease, n number; PLWH people living with HIV, TAF tenofovir alafenamide, TDF tenofovir disoproxil fumarate. a Pre-switch: ASCVD calculated ≤ 6 months before the last lipid panel on TDF; statin prescription at or after the last lipid panel on TDF; Post-switch: ASCVD calculated ≤6 months before the first lipid panel on TAF; statin prescription at or after the first lipid panel on TAF reported here [19][20][21][22]. However, other observational studies reported larger statistically significantly increases in lipids for up to 6 months after switch [18].…”

“…Of note, studies that estimated changes in CHOL/HDL ratio found only negligible differences after a switch from TDF to TAF [20][21][22]. However, despite the CHOL/HDL ratio being a predictor of cardiovascular disease risk, statistically significant increases in the ASCVD risk were observed in one cohort [21], although there was no change in the D:A:D coronary heart disease score or the Framingham risk score in another [22]. In addition, the ATPIII guidelines focus on thresholds for treatment that are based on total, LDL and HDL cholesterol and treatment targets focused on LDL cholesterol, as these are most relevant to overall risk of CVD events.…”

“…Nonetheless, many people living with HIV (PLWH) on stable TDF-containing regimens have been switched to TAF to avoid potential bone and renal toxicity [14]. The impact of switching directly from TDF to TAF on lipids has been explored in a few randomized controlled trials (RCTs) [15][16][17] and small observational studies [18][19][20][21][22]. While these studies showed small but statistically significant increases in lipid levels after switching away from TDF at a population level, the clinical relevance of these changes, specifically in relation to risk of cardiovascular disease, remains unclear, as does the real-world impact of removing TDF on lipids in clinical practice.…”

Real-world efficacy and safety of switching to bictegravir/emtricitabine/tenofovir alafenamide in older people living with HIV

“…However, only 54% of patients in our cohort were switched from regimens containing cobicistat or ritonavir, and 25% were switched from regimens containing TDF. These results are somewhat unusual given the known lipid-lowering effects of TDF compared with TAF [ 29 – 31 ] and suggest that B/F/TAF may be more “lipid-neutral” compared with other ARV regimens. Given the increased risk of vascular disease and metabolic complications among older PLWH, [ 4 ] these data are critical and highlight B/F/TAF as a potentially “lipid-friendly” ARV option for this population.…”