Tenofovir alafenamide (TAF), a new formulation that produces higher drug levels in cells but allows for lower dosing, was as effective as the current tenofovir disoproxil fumarate (TDF) formulation, but had less impact on markers of kidney function and bone turnover, researchers reported yesterday at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Denver.
Tenofovir (Viread, also in the Truvada, Atripla, Eviplera and Stribild coformulations) is one of the most widely used antiretroviral drugs. It is highly effective and generally regarded as safe and well-tolerated. However, it can cause kidney toxicity in susceptible individuals and is associated with bone loss that begins soon after starting treatment. The long-term consequences of these side-effects are a growing concern in light of guidelines recommending earlier treatment initiation and expanding use of Truvada for pre-exposure prophylaxis (PrEP).
Gilead Sciences' new TAF formulation produces fivefold higher concentrations of active tenofovir diphosphate in cells that harbour HIV, but drug levels in the blood remain much lower compared with TDF. This enables reduced dosing that is expected to have a less detrimental effect on the kidneys and bones.
Paul Sax from Brigham and Women's Hospital in Boston presented late-breaking results from a phase 2 study comparing TAF at 10mg and TDF at 300mg, both as part of a single-tablet regimen that also includes the integrase inhibitor elvitegravir, cobicistat (a pharmacoenhancer or 'booster') and FTC (emtricitabine). The TDF-containing coformulation is marketed as Stribild; the TAF version is not yet approved.
