The Lipid-Lowering Effect of Tenofovir/Emtricitabine: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial

Santos, José Ramón; Saumoy, María; Curran, Adrían; Bravo, Isabel; Llibre, Josep M; Navarro, Jordi; Estany, Carla; Podzamczer, Daniel; Ribera, Esteban; Negredo, Eugènia; Clotet, Bonaventura; Paredes, Roger

doi:10.1093/cid/civ296

Cited by 110 publications

(83 citation statements)

References 23 publications

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“…At weeks 24 and 48, there were small, statistically significant differences in increases in total cholesterol, LDL cholesterol, and HDL cholesterol for participants receiving TAF compared with those receiving TDF, but no difference in the TC:HDL ratio, which is associated with cardiovascular risk (Deeks et al, 2013, Wilson et al, 1998, D'Agostino et al, 2008, Goff et al, 2014). These findings are consistent with what has been seen in other TAF vs TDF studies (Sax et al, 2015, Mills et al, 2015, Wohl et al, 2016) and are thought to be due to greater plasma TFV concentrations with TDF (Wohl et al, 2016, Tungsiripat et al, 2010, Santos et al, 2015, Mulligan et al, 2013, Behrens et al, 2012, Patel et al, 2014). Traditional lipid panels may underestimate cardiovascular risk in HIV-infected individuals, (Munger et al, 2015) and there is growing appreciation that pro-inflammatory lipids may contribute to immune activation in persons infected with HIV, including oxidized LDL, as levels of oxidized LDL have been associated with levels of sCD14 in this population (Zidar et al, 2015, Hileman et al, 2016, Nou et al, 2016).…”

Section: Discussionsupporting

confidence: 90%

Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide

et al. 2016

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BackgroundInitiation of antiretroviral therapy (ART) and subsequent virologic suppression reduces immune activation and systemic inflammation.MethodsWe examined longitudinal changes in biomarkers of monocyte activation (sCD14, sCD163), and systemic (IL-6, hsCRP, sTNFR-I and D-dimer) and vascular (Lp-PLA2) inflammation in a subgroup (N = 100 per arm) of participants enrolled in a randomized, placebo-controlled trial comparing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; TAF) to E/C/F/tenofovir disoproxil fumarate (E/C/F/TDF; TDF) in treatment-naïve adults.ResultsFor 194 participants (TAF, 98; TDF, 96), baseline levels of biomarkers did not differ by treatment arm; there were no differences in biomarker values between groups at weeks 12, 24, or 48 (p > 0.05), except IL-6 at week 12 (p = 0.012). Among all participants (combining groups), there were statistically significant declines from baseline observed for D-dimer, sCD163, and sTNFR-1 by week 12 and IL-6 by week 24. The proportion of participants with Lp-LA2 levels < 200 ng per mL (p = 0.250) or hsCRP levels < 3000 mg per L (p = 0.586) was unchanged through week 48.ConclusionsWe observed equivalent declines in biomarkers of monocyte activation and systemic inflammation in treatment-naïve adults treated with TAF or TDF for 48 weeks, suggesting that TAF and TDF have equivalent impact on immune activation and inflammation.

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Section: Discussionsupporting

confidence: 90%

Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide

et al. 2016

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“…Treatment with TDF‐containing regimens has consistently been associated with lower lipids compared with non‐TDF‐containing regimens, an effect thought to be a dose‐related effect of plasma tenofovir on reducing select lipid parameters 15, 16, 17, 18. The changes in fasting lipids seen in Study 1216 are consistent with differences seen in treatment‐naïve patients as well as in other studies evaluating the switch to TAF from TDF while maintaining other antiretroviral regimen components 4, 5.…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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“…Treatment with TDF has consistently been associated with lower lipids compared with other regimens in treatment-naive or virologically suppressed individuals. 22,23 This TDF lipid effect is thought to be associated with the plasma level of TFV. 22,24 In this study, participants switching from TDF-containing regimens showed increases in total, high, and low-density lipoprotein cholesterol and triglycerides, likely related to the significant reductions in plasma TFV concentrations.…”

Section: Discussionmentioning

confidence: 99%

Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

Post

Tebas

Clarke

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Abstract:Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30–69 mL/min who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function.

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The Lipid-Lowering Effect of Tenofovir/Emtricitabine: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial

Abstract: NCT01458977.

Cited by 110 publications

References 23 publications

Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide

Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide

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

Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

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