Tenofovir Alafenamide — Just Different or Better?

Summary and Comment |
May 5, 2015

Tenofovir Alafenamide — Just Different or Better?

  1. Charles B. Hicks, MD

An early version of tenofovir that was not initially developed is now poised to become the preferred formulation, based on comparable efficacy and diminished toxicity.

  1. Charles B. Hicks, MD

Tenofovir disoproxil fumarate (TDF) is a component of most recommended initial antiretroviral therapy (ART) regimens in the DHHS HIV Treatment Guidelines. Although generally well tolerated, it is associated with greater reductions in bone-mineral density than other reverse transcriptase inhibitors and occasionally causes significant renal toxicity. Both of these adverse events are related to tenofovir plasma levels. Another tenofovir prodrug, tenofovir alafenamide (TAF), delivers high intracellular tenofovir concentrations with 90% lower plasma drug concentrations, suggesting that it may have less toxicity than TDF. Now, researchers have conducted two manufacturer-sponsored, double-blind, multinational clinical trials to explore this issue.

In both trials, treatment-naive, HIV-infected adults with estimated glomerular filtration rates (GFR) >50 mL per minute were randomized to receive the currently available single-pill combination of elvitegravir, cobicistat, FTC, and TDF (E/C/FTC/TDF) or a similar investigational single-pill combination in which the 300 mg of TDF was replaced with 10 mg of TAF (E/C/FTC/TAF). In all, 1733 participants (median GFR, >110 mL/min) received at least one study-drug dose. At follow-up week 48, E/C/FTC/TAF was noninferior to E/C/FTC/TDF in the proportion of participants with HIV suppression to ≤50 copies/mL (92% and 90%, respectively; adjusted difference, 2.0%; 95% confidence interval, −0.7% to 4.7%). Compared with E/C/FTC/TDF recipients, E/C/FTC/TAF recipients had significantly smaller mean serum creatinine increases, less proteinuria, and smaller bone-mineral–density decreases at both the spine and the hip. Increases in fasting lipid levels were greater with E/C/FTC/TAF than with E/C/FTC/TDF.


The investigational integrase inhibitor–based combination pill formulated with TAF rather than TDF appears to be highly efficacious in suppressing HIV RNA while offering meaningful advantages over its predecessor in reducing risks for renal and bone toxicity. In the future, TAF will likely become the preferred version of tenofovir, particularly since the small amounts required facilitate single-pill combination regimens. When TDF becomes generic (anticipated in 2017), cost considerations may lead to further assessments of the clinical importance of these relatively small differences.

Paul E. Sax, MD, is an author of this study and a member of the NEJM Journal Watch Infectious Diseases editorial board but had no role in selecting or summarizing this article.

Editor Disclosures at Time of Publication

  • Disclosures for Charles B. Hicks, MD at time of publication Consultant / Advisory board GeoSentinel Surveillance Network (Special Advisor) Editorial boards UpToDate; Clinical Infectious Diseases; International Health; Infectious Diseases in Clinical Practice; Travel Medicine and Infectious Diseases


Reader Comments (1)

Jorge Vergara Physician, Infectious Disease, Hospital

It's very interesting the superior performance TAF over TDF. May be we must wailt for the chance in the popular combination with Emtricitabina; and we need more studies about the use the Cobocistat

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.