Bictegravir HIV integrase inhibitor, Treatment of HIV-1 infection

摘要

Since their introduction a decade ago, integrase strand transfer inhibitors (INSTIs) have found a place in HIV treatment guidelines as standard parts of antiretroviral regimens. These agents block a vital step in viral replication: the insertion of viral DNA into the host genome. Key considerations for selection of an INSTI are whether it can be given once daily, if it has to be taken with food, its side effect profile and the risk of the emergence of resistance to the drug. Bictegravir is an INSTI in advanced development which has shown potent, selective inhibition of HIV-1 replication, a reduced potential for the selection of resistance mutations and activity against INSTI-resistant variants through once-daily, unboosted administration. Bictegravir monotherapy in a phase Ib trial and its addition to emtricitabine/tenofovir alafenamide fumarate (FTC/TAF) in a phase II study showed the potential for viral suppression with favorable tolerability. A single tablet formulation combining bictegravir and FTC/TAF has reached phase III evaluation, where the primary endpoint has been met in four studies assessing its use in treatment-naive patients and virologically suppressed patients switching from another treatment regimen. A new drug application was submitted to the FDA and another is planned for Europe for the fixed-dose combination.