Brecanavir is an experimental anti-HIV drug currently under development by GlaxoSmithKline. It was previously known as GW-640385. It belongs to the protease inhibitor class of anti-HIV drugs.

Test-tube data suggest that it has activity against virus with resistance to the currently available protease inhibitors, and that it is more powerful against wild-type HIV that existing protease inhibitors, being active at concentrations much lower than most existing protease inhibitors.

The optimal dose of brecanavir in early trials was found to be 300mg, boosted with 100mg ritonavir (Norvir) twice a day^[1]. Ritonavir increases the levels of brecanavir in the blood.

Ritonavir-boosted brecanavir has also been shown to be safe and effective in clinical trials at this dose, in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). In an ongoing phase II trial of the drug in 31 patients, six of whom had resistance to currently-available protease inhibitors, 77% of patients had a viral load below 50 copies/ml after 24 weeks, with no differences between protease inhibitor-resistant and -sensitive patients. No severe side-effects were seen in the studies, although tiredness, gastrointestinal disturbances and elevations in blood fat levels were observed, as is common for many protease inhibitors^[2].

Unlike some other protease inhibitors, ritonavir-boosted brecanavir does not have a significant interaction with the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir (Viread)^[3].

In test-tube studies, a number of mutations in the protease gene have been associated with brecanavir resistance. These include L10F, G16E, E21K, A28S, M46I, F53L and A71V. Mutations in the Gag gene have also been linked to resistance^[4]. Further studies are needed to determine the relative impact of these mutations on brecanavir’s activity in patients.

Brecanavir is currently being tested in phase IIb / III trials.