Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project

Tang, Eric C.; Vittinghoff, Eric; Anderson, Peter L.; Cohen, Stéphanie; Doblecki-Lewis, Susanne; Bacon, Oliver; Coleman, Megan; Buchbinder, Susan; Chege, Wairimu; Kolber, Michael A.; Elion, Richard; Shlipak, Michael G.; Liu, Albert Y.

doi:10.1097/qai.0000000000001566

Cited by 36 publications

(49 citation statements)

References 25 publications

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“…The overall reduction and intermittent exposure to TDF/ FTC in our study as compared to a daily regimen, may explain the better renal safety of on-demand PrEP. As already reported with daily PrEP [13,15], we found a doseresponse relationship between recent TDF exposure (prior two months or prior week) and a lower eGFR at the following visit, which strongly supports that an overall reduction of exposure to TDF/FTC may have a positive impact on renal function. The intermittent nature of TDF/FTC exposure is also important to consider with on-demand PrEP according to the reported large inter and intra-participant variability in pill use over time in the study [6].…”

Section: Discussionsupporting

confidence: 89%

“…However, with the global roll-out of PrEP programmes, new PrEP users have emerged with higher risk of kidney dysfunction on TDF. Previous studies on daily PrEP highlighted that a baseline age >40 years or a baseline eGFR ≤ 90 mL/min/1.73 m 2 were associated with a greater eGFR reduction [13][14][15]. In our study, we did not find that participants at-risk of renal dysfunction (age >40 years, eGFR at baseline <90 mL/min/1.73 m 2 or hypertension) had a significantly greater slope of eGFR reduction over time, suggesting that on-demand PrEP may remain safe in this population.…”

Section: Discussionmentioning

confidence: 99%

“…Pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) – emtricitabine (FTC) raises a lot of expectations to hamper HIV epidemic due to its high effectiveness to prevent HIV acquisition in individuals at high risk of infection . However, as already reported in HIV‐infected patients , both PrEP clinical trials and cohorts have shown that the daily use of TDF/FTC in men who have sex with men (MSM), intravenous drug users or serodiscordant couples was associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR) and/or creatinine clearance , especially in users with a baseline eGFR < 90 mL/min/1.73 m 2 , an age >40 years or with higher tenofovir exposure . With the global rollout of PrEP programmes, this concern merits close consideration and highlights the need to find new strategies to improve the renal safety of PrEP.…”

Section: Introductionmentioning

confidence: 99%

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Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

et al. 2020

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Introduction Daily pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on‐demand PrEP with TDF/FTC in HIV‐1 uninfected men. Methods We used data from the randomized double‐blind placebo‐controlled ANRS‐IPERGAY trial and its open‐label extension conducted between February 2012 and June 2016 among HIV‐uninfected MSM starting on‐demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results During the blind phase, with a median follow‐up of 9.4 months, the mean decline slope of eGFR from baseline was −0.88 and −1.53 mL/min/1.73 m2 per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 m2 per year (p = 0.27). Including both phases, 389 participants started on‐demand TDF/FTC with a median follow‐up of 19.2 months and a mean decline of eGFR from baseline of −1.14 mL/min/1.73 m2 per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m2 (p = 0.44), age >40 years (p = 0.24) or hypertension (p = 0.21). There was a dose‐response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of −0.88 mL/min/1.73 m2 between >15 pills/month vs. ≤15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to ≤2 ng/mL: >2 to ≤10ng/mL: −0.98 mL/min/1.73 m2, >10 to ≤40ng/mL: −1.28 mL/min/1.73 m2, >40 ng/mL: −1.82 mL/min/1.73 m2, p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m2 during the OLE phase. No case of Fanconi syndrome was reported. Conclusions The renal safety of on‐demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

et al. 2020

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“…The US PrEP Demonstration Project was an open‐label study that enrolled 557 MSM and transgender women initiating FTC/TDF for PrEP in San Francisco, Miami, and Washington, D.C. (Table ) . By the first 12 weeks on FTC/TDF, serum creatinine (S cr ) was found to have increased 0.03 mg/dl from baseline (p<0.0001) but remained stable thereafter up to 48 weeks . This change correlated with a creatinine clearance (Cl cr ) decrease of 4.8 ml/minute.…”

Section: Discussionmentioning

confidence: 99%

Review of Real‐World Implementation Data on Emtricitabine‐Tenofovir Disoproxil Fumarate as HIV Pre‐exposure Prophylaxis in the United States

2019

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The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012. Since then, Centers for Disease Control and Prevention guidelines for the use of PrEP have been published and implemented into clinical practice throughout the United States. A number of published open-label and PrEP demonstration projects have evaluated the real-world use of PrEP including analysis of the barriers to its use and addressing major concerns. Despite the approval of FTC/TDF for PrEP, its use for this indication relies on patient and provider acceptance, and its effectiveness requires patient adherence and retention in care during periods of high-risk behaviors. Concerns regarding the use of PrEP in healthy individuals persist and include medication adverse effects including renal dysfunction and bone mineral density loss; risk compensation leading to HIV infections, sexually transmitted infections, and unintended pregnancies; and the development of drug resistance in the event of seroconversion. The cost-effectiveness of PrEP continues to be assessed with the greatest cost-effectiveness remaining in those at highest risk of acquiring HIV. Additionally, cases of HIV acquisition in individuals who are adherent to PrEP highlight scenarios in which PrEP is not 100% effective including against the transmission of drug-resistant HIV strains. This review examines data on the implementation of PrEP outside the setting of clinical trials with the aim of providing clinicians with a summary of the current barriers and opportunities for PrEP use with a specific focus on the role of pharmacists in the optimization of PrEP implementation. KEY WORDS HIV, pre-exposure prophylaxis, emtricitabine, tenofovir disoproxil fumarate.

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“…In the real world, kidney impairment was found among TDF-treated HIV-positive patients, who sometimes experienced renal failure, Fanconi syndrome (Coutinho & Prasad, 2013;Paxton, Hope, & Jaffe, 2007), and proximal renal tubulopathy. At the same time, proteinuria accompanies creatinine elevation (Tang et al, 2018). In short, side effects of FTC/TDF have become a concern.…”

Section: Side Effects Of Prepmentioning

confidence: 99%

Efficacy, Adherence and Side Effects of PrEP for HIV-1 Prevention

Fang¹,

Mphoyi²,

Motake³

et al. 2019

IJB

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Each year, approximately two million new HIV infections are reported worldwide. About one decade ago, a company called Gilead Sciences Inc. discovered a new HIV prevention method named as pre-exposure prophylaxis (PrEP). When high adherence was kept among high-risk population, PrEP efficacy could reach as high as 99%. However, the adverse effects have been reported from time to time, including low efficacy in certain cases, adherence difficulties and medicinal side effects. In this review, we would summarize the progress of PrEP since its introduction in order to provide insights for HIV prevention.

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Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project

Cited by 36 publications

References 25 publications

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

Review of Real‐World Implementation Data on Emtricitabine‐Tenofovir Disoproxil Fumarate as HIV Pre‐exposure Prophylaxis in the United States

Efficacy, Adherence and Side Effects of PrEP for HIV-1 Prevention

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