TAF vs. TDF (Original Tenofovir) -- Improvements in Safety

October/November 2015

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Focus on the Kidneys

The old formulation of tenofovir, TDF, was known to cause kidney injury in some participants. In the present studies, no participants who took TAF quit because of kidney-related injury. In contrast, four participants who took TDF quit the study because of kidney injury that either resulted in reduced functioning of these vital organs or because of inflammation.

A common way of assessing kidney health is with a blood test for levels of a protein called creatinine, which is then used to calculate the eGFR (estimated glomerular filtration rate). Decreased eGFR over time suggests ongoing kidney dysfunction or injury. In general, decreases in eGFR among users of a TAF-based regimen were very mild.

Using sophisticated analyses of proteins in the urine, researchers found that levels of these proteins were decreased in a subset of TAF users and increased in a subset of TDF users. This pattern suggested that a TAF-based regimen is relatively safer for the kidneys than a TDF-based regimen.


The proteins assessed were as follows:

  • urinary protein to creatinine ratio
  • urinary albumin to creatinine ratio
  • beta2-microglobulin

Another protein in the urine that was assessed was retinol-binding protein. Levels of this protein were mildly elevated in TAF users compared to being significantly elevated among some TDF users. This suggests that use of a TDF-based regimen is associated with a degree of kidney inflammation and that TAF is generally safe.

Bear in mind that urinary assessments of beta2-microglobulin and retinol-binding proteins are not routinely done in most clinics. Rather, they are largely research-based tools.

Changes in Bone Mineral Density

In general, HIV-positive people are at risk for decreased bone mineral density, perhaps because of the inflammation caused by chronic infection with this virus and perhaps other reasons. For more about risk factors for thin bones, see Reduced bone density and HIV in TreatmentUpdate 189.

Overall, in the present studies, all participants developed thinner bones. Other clinical trials have found that people who initiate ART do experience thinning bones; however, bone density then stabilizes between two and four years after ART initiation.

On average, participants taking a TAF-based regimen lost about 2% of bone density in their spine compared to a loss of 3% among participants who used a TDF-based regimen.

Users of a TAF-based regimen lost about 1% of the bone density in their hips compared to a loss of 3% among TDF users.

These differences in the loss of bone density between regimens were statistically significant.

Although eight cases of bone fractures occurred (one in a person taking a TAF-based regimen and the other seven in those taking a TDF-based regimen), these fractures were not related to the study drugs. Rather, they occurred because of violence or accidents.

Impact on Fatty Substances in the Blood (Lipids)

Researchers found that increases in the levels of lipids (cholesterol and triglycerides) occurred in tests of blood samples taken when participants were fasting.

Participants taking TAF-based regimens were more likely to have increases in the following:

  • total cholesterol
  • bad cholesterol (LDL-C)
  • good cholesterol (HDL-C)
  • triglycerides

Overall, these changes would seem to be unfavourable. However, when looking at the ratio of total cholesterol to HDL-C, participants who took TAF-containing regimens had identical results to participants who took a TDF-containing regimen. This finding suggests that the risk for cardiovascular disease (heart attack, stroke) was the same regardless of which form of tenofovir the participants used.

Slightly more people taking a TAF-based regimen (4%) had to start lipid-lowering therapy than people who took a TDF-based regimen (3%). This difference was not statistically significant.

Key Points

A regimen based on TAF or TDF seems to be roughly equivalent in effectiveness.

A TAF-based regimen has a reduced potential for causing kidney injury and thinning bones than a TDF-based regimen.

The present studies had low proportions of women.

Long-term studies of TAF-containing regimens are needed, both in treatment-experienced people and in those who are initiating ART with such a regimen. This will better help doctors and patients understand the safety of TAF.

Beginning in 2016, Gilead Sciences will begin the process of gradually introducing TAF as an alternative to TDF in its fixed-dose formulations. As mentioned earlier in this issue of TreatmentUpdate, the first new TAF-containing regimen is an alternative to Stribild called Genvoya.

In cases where a pharmacological booster (such as ritonavir or cobicistat) is used in a regimen, the dose of TAF recommended by the manufacturer is likely to be 10 mg per day. In cases where no pharmacological booster is used, the daily dose likely to be recommended is 25 mg per day.


  1. Gilead Sciences. European CHMP Adopts Positive Opinion for Gilead's Single Tablet Regimen Genvoya® (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for the Treatment of HIV. Press release. 25 September 2015.
  2. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015 Jun 27;385(9987):2606-15.
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.

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