Switching Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in a Real Life Setting

What Are the Implications?

C Schwarze-Zander; H Piduhn; C Boesecke; S Schlabe; B Stoffel-Wagner; JC Wasmuth; CP Strassburg; JK Rockstroh

Disclosures

HIV Medicine. 2020;21(6):378-385. 

In This Article

Abstract and Introduction

Abstract

Objectives: Development of novel antiretrovirals aims at reducing long-term toxicities. Tenofovir disoproxil fumarate (TDF) has been associated with potential nephrotoxicity. The aim of our study was to assess the impact of switching from TDF to tenofovir alafenamide (TAF) on functional nephropathy and lipid parameters in a real-life setting.

Methods: We retrospectively analysed data from 347 HIV-infected patients switching from a TDF- to a TAF-containing regimen between April and December 2016. Sociodemographic, clinical and laboratory data were collected at TDF-to-TAF switch, and at 3 and 6 months thereafter. Proteinuria and albuminuria were classified according to Kidney Diseases Improving Global Outcomes (KDIGO) guidelines.

Result:s At time of switch, moderately and severely increased proteinuria was detected in 32% and 8% of patients, respectively; however, urine dipstick analysis was negative in 84% and 42%, respectively. Moderately and severely increased albuminuria was found in 17% and 3% of patients, respectively. In patients with a urinary protein-to-creatinine ratio (UPCR) ≥ 150 mg/g, the mean value declined from 416 mg/g at baseline to 272 mg/g (P < 0.001) and 242 mg/g (P < 0.001) after 3 and 6 months, respectively. Patients with an albumin-to-creatinine ratio (UACR) ≥ 30 mg/g showed no significant decrease of albuminuria. Mean total cholesterol increased from 187 mg/dL at baseline to 202 (P < 0.001) and 208 mg/dL (P < 0.001) at 3 and 6 months, respectively, and mean low-density lipoprotein (LDL) cholesterol increased from 114 mg/dL at baseline to 124 (P < 0.001) and 128 mg/dL (P < 0.001), respectively. As mean high-density lipoprotein (HDL) cholesterol increased from 50 mg/dL at baseline to 54 (P < 0.001) and 57 mg/dL (P < 0.001) at 3 and 6 months, respectively, the LDL:HDL ratio remained stable.

Conclusions: In an aging HIV-infected cohort, proteinuria and albuminuria were common findings and were underdiagnosed via urine dipstick. Our real-life data suggest that laboratory markers of moderately/severely increased proteinuria improved after TDF-to-TAF-switch. Lipid profiles were not aggravated. Long-term follow-up is needed to determine the clinical benefit of the TDF-to-TAF switch.

Introduction

The availability of highly effective combination antiretroviral therapy (cART) has transformed HIV infection into a manageable disease, with a consequent consistent decrease in HIV-related mortality. However, the rates of non-AIDS-defining comorbidities have increased considerably. In particular, chronic kidney disease (CKD) plays an important role in morbidity and mortality in people living with HIV (PLWH).[1,2]

In its early stages, CKD with urine protein loss is often clinically asymptomatic. CKD in PLWH may develop as a result of (1) HIV-associated nephropathy, which is most prevalent in patients of African ethnicity, (2) viral coinfections, such as hepatitis B and C, and (3) tubular toxicity of ART. In addition to progression to end-stage renal disease, CKD is also associated with a higher risk for cardiovascular disease.

Thus, the long-term success of cART may be limited by adverse events associated with the antiretroviral regimen. For tenofovir disoproxil fumarate (TDF), the main adverse events are potential nephrotoxicity, including proximal renal tubulopathy, and reduction in bone mineral density.[3] In comparison to TDF, the more recently licensed pro-drug formulation tenofovir alafenamide (TAF), identified in 2004 as an alternative to TDF,[4] produces a 6.5 times higher intracellular concentration of the phosphorylated moiety tenofovir in peripheral blood mononuclear cells. Thus, the oral dose can be lowered substantially from 300 mg TDF to 25 mg TAF daily.[5] Accounting for the boosting effects of ritonavir and cobicistat, the TAF dose is furthermore adjusted from 25 to 10 mg daily in the presence of these pharmacokinetic enhancers. In several double-blind phase 3 trials, the noninferiority of TAF vs. TDF in terms of virological efficacy has been demonstrated in treatment-naïve and virologically suppressed patients.[6–9] Pharmacodynamic studies have suggested that the lower tenofovir levels translate into less exposure to the drug in the kidneys and the bones, with possible favourable implications for adverse effects. Therefore, TAF is predicted to give the same clinical efficacy with potential improvements in tolerability, which is especially important in an aging HIV-infected population.

There has been some concern about worsening of lipid profiles after switching from TDF to TAF. The lipid-lowering effect of TDF is dependent on the concentration of serum TDF. Switching from a TDF- to a TAF-containing regimen has been found to lead to significantly increased low-density lipoprotein (LDL) and total cholesterol levels. However, in randomized studies, the total cholesterol:high-density lipoprotein cholesterol (HDL) ratio remained unchanged in patients on TAF-containing regimens.[6,8,10,11]

In the present study, we aimed to determine changes of proteinuria and albuminuria in an aging HIV-positive population on ART switching from TDF to TAF. We further examined the impact of switching from a TDF- to a TAF-containing regimen on lipid profiles in a real-life setting.

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