Tenofovir disoproxil fumarate can cause renal and bone toxic effects due to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. It is postulated that tenofovir alafenamide based regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens.
An editorial notes that it remains to be seen whether the small differences in creatinine clearance decline and bone mineral density loss reported between the two drugs in this 48 week trial will translate into clinically meaningful differences in kidney and bone health. It adds that if post-marketing experience confirms the improved safety profile, this would have implications for HIV treatment, as a safer drug would reduce costs related to toxic effect monitoring and adverse event management. Furthermore, these cost savings could be magnified by reduced manufacturing costs because tenofovir alafenamide is effective at doses of 10–25mg of the active pharmaceutical ingredient, compared with the standard tenofovir disoproxil fumarate dose of 300mg per day. The commentators also note that beyond the potential implications for people with HIV, a safer and less expensive tenofovir prodrug could also offer benefits for the treatment of hepatitis B virus infection and the prevention of HIV infection in high-risk populations. They conclude that real-world clinical experience will ascertain whether tenofovir alafenamide offers meaningful safety or cost benefits over currently approved treatment.
A new drug application has been filed with the FDA seeking approval to market two strengths of a fixed-dose combination of emtricitabine and tenofovir alafenamide (F/TAF) for HIV-1 infection in patients aged 12 years and older, alongside other antiretrovirals. Gilead plans to submit a regulatory application for F/TAF in the EU in second quarter of 2015.