Tenofovir-Associated Kidney Toxicity in HIV-Infected Patients: A Review of the Evidence

Hall, Andrew M.; Hendry, Bruce M.; Nitsch, Dorothea; Connolly, John

doi:10.1053/j.ajkd.2011.01.022

Cited by 328 publications

(294 citation statements)

References 54 publications

Supporting

Mentioning

267

Contrasting

Unclassified

Order By: Relevance

“…This event was precipitated by prerenal acute kidney injury, which can cause elevated plasma concentrations of tenofovir as renal clearance of this TDF metabolite declines. TAF use results in 91% lower plasma concentrations of tenofovir than TDF and thus renal toxicities have rarely been seen in patients taking TAF 12, 13. Participants switching from EFV/FTC/TDF to RPV/FTC/TAF in Study 1160 did have an immediate small increase in serum creatinine consistent with inhibition by RPV of creatinine secretion in the renal tubule 14.…”

Section: Discussionmentioning

confidence: 98%

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96‐week results from two randomized clinical trials

Hagins

Orkin

et al. 2018

HIV Medicine

View full text Add to dashboard Cite

ObjectivesThe single‐tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV‐1‐infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF.MethodsWe conducted two distinct randomized, double‐blind, active‐controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV‐1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV‐1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96.ResultsWe randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) −4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI −4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment‐emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001).ConclusionsSwitching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment‐emergent resistance.

show abstract

Section: Discussionmentioning

confidence: 98%

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96‐week results from two randomized clinical trials

Hagins

Orkin

et al. 2018

HIV Medicine

View full text Add to dashboard Cite

show abstract

“…Tenofovir disoproxil fumarate (TDF) is an NtRTI that has been licensed by the FDA for use in children >2 years of age [131]; TDF can cause FS [132]. Several mechanisms of TDF nephrotoxicity have been investigated: It enters proximal tubule cells through basolateral OATs and exits by using an apical transporter, the multidrug-resistance-associated protein 4 (MRP 4) [133,134]. TDF toxicity in the proximal tubule cell can lead to damaged and dysmorphic mitochondria, with loss of matrix cristae; in some cases, it can result in giant mitochondria.…”

Section: Antiretroviralsmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

View full text Add to dashboard Cite

The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

show abstract

“…Several case reports and small case series demonstrated a potential risk of TDF nephrotoxicity (10). It has been reported that TDF nephrotoxicity usually presents acute tubular necrosis with or without Fanconi syndrome (11). A recent study showed that a characteristic feature of TDF nephrotoxicity in renal biopsy is eosinophilic intracytoplasmic inclusions within proximal tubular epithelial cells, corresponding to the giant mitochondria seen ultrastructurally.…”

Section: Discussionmentioning

confidence: 99%

Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

et al. 2012

View full text Add to dashboard Cite

This report presents a human immunodeficiency virus (HIV) patient that developed a slowly progressive renal impairment over years under highly active antiretroviral therapy (HAART). The renal biopsy showed diffuse tubulointerstitial nephritis accompanied by crystal formations that were surrounded by multinuclear giant cells. Furthermore, rod-like crystals were detected in the urinary sediments. Tenofovir and Atazanavir were thought to be the causative drugs for the renal injury. Therefore, the possibility of HARRT-induced nephrotoxicity should be considered in HIV-infected patients, even though the activity of HIV is controlled by such therapies.

show abstract

Tenofovir-Associated Kidney Toxicity in HIV-Infected Patients: A Review of the Evidence

Cited by 328 publications

References 54 publications

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96‐week results from two randomized clinical trials

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96‐week results from two randomized clinical trials

Drug-induced acid-base disorders

Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

Contact Info

Product

Resources

About