Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate

Gupta, Samir K.; Post, Frank A.; Arribas, José Ramón; Eron, Joseph J.; Wohl, David A.; Clarke, Amanda; Sax, Paul E.; Stellbrink, Hans‐Jürgen; Eßer, Stefan; Pozniak, Anton; Podzamczer, Daniel; Waters, Laura; Orkin, Chloe; Rockstroh, Jürgen K.; Mudrikova, Tatiana; Negredo, Eugènia; Elion, Richard; Guo, Susan; Zhong, Lijie; Carter, Christoph; Martin, Hal; Brainard, Diana M.; SenGupta, Devi; Das, Moupali

doi:10.1097/qad.0000000000002223

Cited by 129 publications

(90 citation statements)

References 36 publications

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“…Our study demonstrates that eGFR slopes improved in individuals who switched from TDF-to TAF-containing ART, particularly in those who experienced rapid eGFR decline or CKD while receiving TDF. These data expand clinical trial experience which has shown that TAF is associated with stable renal function, even in those with mild/moderate CKD, and a more favourable renal biomarker profile than TDF [12,13]. Moreover, TAF had been successfully used and was shown to have no significant effect on biomarkers of renal tubular function in individuals who experienced proximal tubulopathy/Fanconi syndrome while receiving TDF [16][17][18][19][20], suggesting that the renal safety of TAF extends to a broad population of people with HIV infection.…”

Section: Discussionsupporting

confidence: 74%

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Ibrahim

Campbell

Bailey³

et al. 2020

HIV Medicine

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Objectives The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. Methods An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time‐updated CD4 cell count and HIV RNA measurements. Results Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was −2.08 [95% confidence interval (CI) −2.24, −1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). Conclusions Significant improvement in eGFR slope was observed in patients who switched from TDF‐ to TAF‐containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

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Section: Discussionsupporting

confidence: 74%

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Ibrahim

Campbell

Bailey³

et al. 2020

HIV Medicine

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“…Tenofovir alafenamide (TAF) is a novel tenofovir pro-drug formulation that achieves high intracellular tenofovir diphosphate concentrations despite 90% lower systemic exposures. Clinical trials have demonstrated similar rates of viral suppression compared with TDF, with reduced effects on kidney and bone biomarkers [9,10]. A clinical trial in people with HIV infection and renal impairment (creatinine clearance 30-70 mL/min) supports the use of TAF in this group and suggests that TAF is generally safe across a broad range of renal pathologies [11].…”

Section: Introductionmentioning

confidence: 99%

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Hamzah

Williams²,

Bailey

et al. 2019

HIV Medicine

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Objectives The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). Methods Individuals with a history of TDF‐associated PRT and currently suppressed HIV infection on a tenofovir‐sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol‐binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016‐003345‐29. Results We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (β 19.6; 95% confidence interval −35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. Conclusions In people with a history of proximal renal tubulopathy while on TDF, 12‐week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long‐term safety of TAF in this group of patients.

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“…Tenofovir alafenamide (TAF), a new prodrug of TFV is stable within plasma and metabolized to TFV mostly within target cells, enabling a small amount of dosing (25mg), which results in low plasma TFV levels and is thus safer to the kidney (50) (Figure 1). High efficacy and tolerability, especially minimal renal toxicity, of TAF have been shown in phase 3 trials and other studies including those which examined treatmentnaïve patients, treatment-experienced patients, and patients with renal impairment (51)(52)(53)(54). The phase 3 study, which randomly compared the efficacy and tolerability of elvitegravir/cobicistat/emtricitabine/TAF and elvitegravir/cobicistat/emtricitabine/TDF among treatment-naïve patients showed that a median change from baseline in creatinine clearance was significantly lower with TAF (-1.6 mL/min) than TDF (-7.7 mL/min) TDF-or ABC-containing ART, those who initiated TDF-containing ART were twice as likely to develop > 10 mL/min/1.73 m 2 decrement in eGFR and ≥ 25% decrement in eGFR than those who initiated ABCcontaining ART (20).…”

Section: Tenofovir Alafenamidementioning

confidence: 95%

“…(91) at week 144 (55). Furthermore, a recent pooled analysis of 26 trials showed the renal safety of TAF over TDF by examining a total of 12,519 person-years of exposure to TAF; there were no cases of proximal renal tubulopathy or Fanconi syndrome, and significantly fewer discontinuations due to renal adverse events in the TAF group than the TDF group (51). A sub-analysis of phase 3 clinical trials, which investigated efficacy and safety of elvitegravir/cobicistat/emcticitabine/TAF extracted the data of Asians and showed comparable efficacy and safety data between Asians and non-Asians (56).…”

Section: Tenofovir Alafenamidementioning

confidence: 99%

Tenofovir nephrotoxicity among Asians living with HIV: review of the literature

Nishijima

Gatanaga

Oka

2019

GHM

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Tenofovir disoproxil fumarate (TDF), prodrug of tenofovir (TFV), is one of the most widely used nucleotide reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infection in resource-rich and resourcelimited settings with proven efficacy and safety, and also for the treatment of hepatitis B infections. However, TDF can cause renal proximal tubular dysfunction and also reduces estimated glomerular filtration rate (eGFR) more than other NRTIs. To date, TDF-associated renal dysfunction is generally regarded as mild and tolerable. However, it is notable that low body weight is one of the risk factors for TFV nephrotoxicity and that Asians are generally of smaller body stature and can be susceptible to such nephrotoxicity, as shown in several cohort studies. Until tenofovir alafenamide (TAF), another prodrug of TFV with minimal renal toxicity, becomes widely accessible for people living with HIV and replaces TDF, it is warranted that physicians who prescribe TDF have a good understanding of TFV nephrotoxicity. This paper reviews recent literature on TFV nephrotoxicity among people living with HIV especially focusing on Asians who might be susceptible to TFV nephrotoxicity due to their lower body weight and discusses implications for clinical care and future directions.

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Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate

Abstract: Supplemental Digital Content is available in the text

Cited by 129 publications

References 36 publications

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Tenofovir nephrotoxicity among Asians living with HIV: review of the literature

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