From TMC114 to darunavir: five years of data on efficacy.

Five years after its initial approval, an overwhelming amount of pivotal data has come out on darunavir/ritonavir. It is the only antiretroviral that has been registered at two different doses, 800/100 mg once-daily or 600/100 mg twice-daily, allowing its administration throughout the entire course of HIV disease, from naive subjects without any HIV-1 resistance to heavily treatment-experienced subjects with widespread triple-class family resistance. Its binding affinity is more than 100-fold higher compared to other protease inhibitors, which poses extreme difficulties for wild-type viruses to develop in vitro resistance to darunavir. It is a preferred option for initial therapy as no subjects developing virologic failure select darunavir resistance mutations in this scenario. It is the default protease inhibitor for early and advanced salvage regimens in subjects with virologic failure. The once-daily darunavir dose has demonstrated non-inferior efficacy against the twice-daily dose in early stages of virologic failure in pretreated subjects without darunavir mutations, both doses retaining the genetic barrier against resistance seen in treatment-naives. With a high potency, superior genetic barrier to HIV-1 resistance development, and favorable pharmacokinetics, it meets the optimal requirements for being a candidate for once-daily antiretroviral monotherapy - a challenging proof-of-concept in HIV medicine. It has demonstrated non-inferior efficacy at 48 weeks against triple therapy in selected pretreated patients with suppressed plasma viremia, without evolution of protease resistance being seen up to 144 weeks. The present article summarizes the clinical implications of the key data on efficacy of darunavir.