TAF/FTC Coformulation Approved
April 28, 2016
The FDA has approved a new 2-NRTI formulation containing tenofovir alafenamide (TAF) 25 mg + emtricitabine (FTC) 200 mg for adults and children ≥12 years of age; its brand name is Descovy. This is a TAF-containing alternative to TDF/FTC (Truvada).
Recommended dosing is 1 tablet PO daily regardless of third agent. Although TAF was studied at a dose of 10 mg when used in combination with PK boosters (ritonavir or cobicistat) and 25 mg in unboosted regimens, a decision evidently was made to produce only a TAF/FTC 25/200 mg coformulation. This appears to be based on the rationale that 25 mg of TAF with PK boosters will result in tenofovir exposure that "will remain substantially lower than that observed with previously approved" TDF formulations; no data are available on the renal or bone safety of TFV 25 mg used concurrently with PK boosters.
As I have discussed in previous pieces (Switching from TDF/FTC to TAF/FTC and TAF: New Data on Tenofovir Alafenamide Fumarate), the use of TAF rather than TDF may result in less adverse effect on kidneys and on bones. However, before switching all your patients from TDF/FTC to TAF/FTC, consider these caveats:
- Safety: As mentioned above, the safety of a 25 mg daily dose of TAF has not been studied with regimens containing PK boosters; in those settings, it was studied at 10 mg daily.
- It is not approved for use if the CrCl is <30 mL/min.
- Drug-drug interactions: TAF is a substrate of p-glycoprotein and may have a number of important drug-drug interactions. For example:
- Cobicistat, ritonavir, atazanavir/ritonavir, darunavir/ritonavir, and lopinavir/ritonavir increase plasma TAF concentrations (note that these studies evaluated the effects on 10 mg of TAF; no data are available for the 25 mg dose of TAF with PK-boosted agents).
- Rifampin, rifabutin, and rifapentine; certain anticonvulsants including phenytoin and phenobarbital; St. John's wort; and boosted tipranavir may decrease plasma TAF concentrations and should not be coadministered with TAF.
- HBV: Data on use of TAF to treat HBV are limited. Pending further study, treatment of HIV/HBV-coinfected patients with TAF/FTC is not recommended (and not approved by the FDA).
- PrEP: No clinical data are available on the use of TAF/FTC as PrEP, and a recent study raised concerns about low levels of active tenofovir in cervical, vaginal, and rectal tissues after receipt of TAF (Tissue Levels of TAF: Too Low for PrEP?). Pending further study, TAF/FTC should not be used as PrEP.
And a final thought: We have become familiar with the possible advantages of lower systemic tenofovir exposure produced by TAF (compared with TDF), eg, possibly lower risk of renal and bone toxicity. The question of possible disadvantages of lower tenofovir levels is explored in a recent editorial in Lancet HIV.(1) The bottom line is that while TAF will be an important tool to treat HIV, there is a scarcity of data in a number of important areas, and we will need more studies to fill gaps in our knowledge of this drug.
The prescribing information for Descovy is available at Drugs@FDA.
1. Boyd MA, Cooper DA. Tenofovir alafenamide: safer, but questions remain. Lancet HIV. 2016 Apr;3(4):e148-9.
Susa Coffey is medical editor of the NCRC. She is a Professor of Medicine at UCSF in the Division of HIV, Infectious Diseases and Global Medicine and a longtime clinician and educator in the HIV at San Francisco General Hospital clinic (“Ward 86”). She also is medical editor of HIV InSite.