Hello. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School. As you probably know, in early April the US Food and Drug Administration (FDA) approved the third tenofovir alafenamide coformulations for the treatment of HIV. This is tenofovir alafenamide plus emtricitabine, or TAF/FTC. The other two have been around for a bit longer. One is the rilpivirine FTC/TAF formulation, and the first one was, of course, the elvitegravir/cobicistat FTC/TAF formulation. Now those two are predominantly used for people who are just starting therapy or have never had treatment failure and are switching to it. But this TAF/FTC formulation could be used in a much broader patient population. As you are aware, there are many, many patients currently receiving TDF/FTC, both treatment-naive and treatment-experienced patients. So, arguably, this is the most important of the three approvals.
All of the clinical studies done so far with TAF-based formulations have shown that TAF, compared with TDF, exerts less of an effect on bone density, is less likely to induce proteinuria—in particular, tubular proteinuria—and, thus far, there have not been any cases of renal disease directly attributed to TAF. There is a slight increase in lipids compared with TDF, and that is because tenofovir levels are so much lower with TAF than TDF. As a result, the lipid-lowering effect of tenofovir isn't seen quite as much. But all in all, TAF does appear to have better safety, and the signature toxicities of tenofovir disoproxil fumarate—renal toxicity and bone toxicity—appear to be diminished.
In some circumstances, we want to be cautious about using TAF. We do not want to use it in patients who are receiving rifampin, either for treatment of tuberculosis or, as I had recently, a patient who needed rifampin for treatment of a Staphylococcus aureus infection. Rifampin significantly lowers TAF levels, and patients already have lower levels because of the fact that the dose is so much lower.
A second area where we need to be cautious is in pregnancy. I do think that, ultimately, TAF/FTC during pregnancy would be a good option, but right now there are very limited data.
The third area where I really caution people against using TAF/FTC is in preexposure prophylaxis. We have clinical trial data from TDF/FTC for preexposure prophylaxis; we have no comparable data for TAF/FTC. When studies had been done looking at tissue levels of tenofovir in patients who received TAF, they were significantly lower than with TDF. On the plus side, there has been a macaque model showing that TAF/FTC may help prevent infection during SIV challenge, but those are animal data. Clinical studies of TAF/FTC for PrEP really haven't been done.
I do want to mention one final thing; it's a little pet peeve of mine. The FDA continues to include a black box warning for all nucleoside analogs about lactic acidosis and hepatic steatosis, and that's true about TAF/FTC as well. Thus far, as far as I'm aware, there have been no cases ever reported for this particular combination. If it's a class effect, it's got to be very, very rare with TAF/FTC. Second, it says that it's not approved for the treatment of hepatitis B. Recently, at the International Liver Congress, we did see data showing that TAF is as effective as TDF for the treatment of people with chronic hepatitis B. I would have no concerns about using TAF/FTC or any of the TAF-based formulations in patients who are hepatitis B–coinfected with HIV.
That's a summary of some of the recent TAF approvals—in particular, the recent one of TAF/FTC. Thank you very much for listening.
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Cite this: TAF/FTC Approved: Benefits and Limitations in Clinical Practice - Medscape - May 20, 2016.
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