Dyslipidaemia after switch to tenofovir alafenamide (TAF)‐based cART regimens in a cohort of HIV‐positive patients: what clinical relevance?

Abstract

ObjectivesSwitching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with low‐density lipoprotein (LDL) above their cardiovascular‐related target.MethodsAll HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV‐related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV‐related target were evaluated after switch to TAF.ResultsOverall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV‐related target after switch to TAF [adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1–5.1], P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7–5.3, P < 0.0001).DiscussionSwitching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.

Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides

“…Several observational studies have investigated changes in lipid levels after a switch from TDF to TAF, with findings aligning with this OPERA study. In studies with postswitch lipid measurements taken a median of 1.5–12 months after switch, statistically significant increases were observed in LDL-C (range, 6–25 mg/dL) and TG (range, 12–21 mg/dL) [ 31 , 32 , 35 , 39 , 40 ]. Only 1 small observational study of 48 PWH switching from TDF to TAF found no significant difference in LDL-C and TG levels over at least 12 months on TAF, although the magnitude of change estimated was comparable to other studies [ 33 ].…”

“…Indeed, in 1 study of PWH switching from TDF to TAF who maintained their anchor agent, increases in lipids were observed after switch, regardless of the regimen. However, the magnitude of change differed by regimen, and when cardiovascular risk was assessed, those using cobicistat were 2.5 times more likely to have an LDL-C level above the cardiovascular target compared with PWH not using cobicistat [ 40 ]. In this OPERA study, while changes in lipids were not estimated for different regimens, the use of PIs and boosting agents was nonetheless controlled for in statistical models.…”

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations

“…have an influence. It has been currently reported, that switch from Tenofovir Disoproxil (TDF) to Tenofovir Alafenamide (TAF) worsens lipid parameters among HIV patients [24,25]. In our study, TAF was the most commonly used antiretroviral drug.…”

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 ]. Nevertheless, the statistically significant increases in lipid levels reported in this OPERA study are consistent with the literature comparing lipid changes with TAF compared to TDF [ 15 – 17 , 28 – 31 ].…”

“…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 – 17 ] and small observational studies [ 18 – 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.…”