Top 10 Clinical Review


Tenofovir Alafenamide Fumarate (TAF) Is FDA Approved: A Top HIV Clinical Development of 2015

December 2, 2015

Just as Google, Facebook, and Apple have become a ubiquitous part of daily life, tenofovir disoproxil fumarate (TDF) is practically unavoidable in the treatment of HIV infection. And, like these tech behemoths, TDF emerged on a scene that was desolate and desperate (remember Netscape Search, MySpace and "mobile" phones the size of a platypus?) and then proceeded to set a new standard. Nucleoside reverse transcriptase inhibitor (NRTI) therapy no longer had to have life-threatening toxicities such as anemia and lactic acidosis or to be dosed twice a day -- and as a bonus it could be coformulated with other antiretrovirals into a single daily tablet. But as anyone who has been burned badly by an operating system update knows all too well, even cherished things can be imperfect.

TDF's problems can be summed up in two words: renal and bone. Although nephrotoxicity at the hands of TDF is not common, serum creatinine elevations in people living with HIV are. Simply the potential for TDF to cause kidney problems triggers worry and a requisite workup for tubulopathy. Less obvious and perhaps more concerning is the effect of TDF on bone mineralization. Initiation of any antiretroviral therapy is associated with declines in bone mineral density (BMD) -- in part a consequence of immune reconstitution that leads to increased bone turnover. However, TDF-containing regimens lead to deeper drops in BMD comparatively, raising concerns about long-term administration in those who are older and at risk for osteopenia/porosis, as well as in the very young whose bones are still developing.

Enter tenofovir alafenamide fumarate (TAF). TAF has made my list of top 10 HIV stories in prior years, but in 2015 a truck load of TAF clinical trial data were delivered, culminating in U.S. Food and Drug Administration (FDA) approval of the drug in November as part of a coformulated single tablet with elvitegravir, cobicistat, and emtricitabine -- what's being marketed as Genvoya.

The data from two large phase-3 treatment-naive trials of TAF versus TDF not only show non-inferior efficacy and better kidney and bone safety for TAF, they wag a finger at its predecessor for its mostly (but not always) subclinical protein-spilling and bone-wasting ways. A series of switch studies also demonstrated TAF's different and minimal impact on bone and renal parameters. In one study, even those with renal insufficiency didn't see their kidneys flinch when given TAF.

The Bottom Line

Frustration with agents in the NRTI class has led to a rising interest in nucleoside-free or -lite regimens. TAF may be coming on the scene just in time -- or perhaps just a tad too late. But, that there is a nucleotide that appears to be the "fairest of them all" in terms of toxicity potential can only be a boon for patients for whom a nuke is desired or required.

To support such use, TAF has been explored from practically every angle, including initial therapy and simplification switch. Other data are supportive of its use in specific populations such as those with renal insufficiency. Studies have answered clearly the question of TAF's efficacy and safety. Less clear is to what extent providers will adopt TAF. First only available in a coformulation with elvitegravir/cobicistat/emtricitabine (FTC), and priced the same as the same combination that included TDF (Stribild), it is expected that a stand-alone TAF/FTC tablet will be available in 2016. Other coformulations with rilpivirine (Edurant) and later darunavir/cobicistat (Prezcobix) will follow. This ubiquity will make using this agent practically inescapable -- whether you like it, or "friend" it, or not.

What are some other top clinical developments of 2015? Read more of Dr. Wohl's picks.

David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.

Copyright © 2015 Remedy Health Media, LLC. All rights reserved.


Reader Comments:

Comment by: Steven S. Muchnick, PhD (San Franisco, CA) Sun., Dec. 6, 2015 at 8:36 pm UTC
No, the FDA did not approve TAF! It approved TAF in combination with other drugs, as proposed and restricted by Gilead. TAF is a major improvement over TDF in several respects, and it certainly ought to be made available as a single drug -- which Gilead has said quite clearly it does not intend to do -- so that it can be used in combination with other non-Gilead meds.
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Comment by: JS Pizzy (South Africa) Sun., Dec. 6, 2015 at 6:22 pm UTC
My boyfriend of 54 is using ARVs, one of the Tenoforvir versions to help ease chronic pain he is suffering after he fractured his right thigh bone 23 years ago. I discovered this after I had been living with him for a month. I want to believe him. We practice safe sex but there are obviously problems of trust. I need to hear this from a medical professional. Save me from embarrassing myself.
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Comment by: Peter Flynn (Tucson, AZ) Sun., Dec. 6, 2015 at 10:13 am UTC
I'm currently taking this and in the future my love will be too. Of the drugs I'm taking and they're all miracles Tenofovir is extremely cool. When one first gets an HIV diagnosis one based on wide spread ignorance can assume they have no more than a year or two to live and I of course did. Now with a viral load approaching undetectacable and a lifelong love to have I'm nothing g but excited to be an HIV survivor and the night I contracted was one of the most jacked up nights of my life and in the heifht of irony it only happened because u was dealing with trauma associated dementia from falling trail running and smashing my right temple on a rock hard. Yes, but three months everything came back in a flood and I knew what it was from taking Abnormal Psychology in college and I was quite startled to realize how missed up I'd been and I also knew it was Neuroplasticity that was the reason. And when I told Dr. Weinnan the chief of neurosurgery at the U/A about it and that I thought the reason was Neuroplasticity he agreed that was what it was. Sadly not all doctors are created equally and to find one who took his Hypocratic oath seriously and didn't bring his ego to every patient interaction was so refreshing and he became a role model for my future career as an RN having been before a professional pilot. Ciao all.

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