In January 2018 darunavir was still the most recent HIV protease inhibitor to reach the market.
In 2006, GlaxoSmithKline discontinued the phase II clinical development of brecanavir, an investigational protease inhibitor for the treatment of HIV, due to insurmountable issues regarding formulation.
In the summer of 2009, GlaxoSmithKline and Concert Pharmaceuticals announced their collaboration to develop and commercialise deuterium-containing medicines. One of them is CTP-518, a protease inhibitor for the treatment of HIV, expected to enter phase I clinical trials in the second half of 2009. CTP-518 is a novel HIV protease inhibitor developed by replacing certain key hydrogen atoms of atazanavir with deuterium. Pre-clinical studies have demonstrated that this modification fully retains the antiviral potency but can evidently slow hepatic metabolism and thereby increase the half life and plasma trough levels. CTP-518, therefore, has the potential to be the first HIV protease inhibitor to eliminate the need to co-dose with a boosting agent, such as ritonavir.