Taking it

Darunavir is licensed in both the European Union and the US for use in both antiretroviral-naive and ART-experienced patients. Boosted darunavir was not approved for use by treatment-naive patients when the latest edition of the BHIVA treatment guidelines went to press. However, the guidelines anticipated that the marketing approval of the drug was likely to change and state that it is an option for patients who initiate antiretroviral therapy with a protease inhibitor-based regimen.

Current BHIVA treatment guidelines advise twice-daily dosing of darunavir (Prezista) at 600mg twice a day, taken with a boosting dose of 100mg ritonavir (Norvir). Darunavir must be taken with food to ensure adequate drug levels in the blood. In the US in late 2008, darunavir was approved for once-daily dosing, using two 400mg tablets taken with 100mg ritonavir in combination with other antiretroviral drugs, and a similar dose was approved in Europe in 2009.

This shift was made on the basis of results from the ARTEMIS study, showing that at 48 weeks, patients randomised to receive darunavir/ritonavir had a non-inferior response to those randomised to lopinavir/ritonavir. Of note, patients who began treatment with a viral load above 100,000 copies/ml had a significantly increased likelihood of achieving undetectable viral load on the boosted darunavir arm of the study.1

In November 2012, an 800mg tablet received US FDA approval, and was approved in Europe in January 2013. This dosage is approved for treatment-naive and treatment-experienced adults with no darunavir resistance, taken with 100mg of ritonavir. It enables people to take one darunavir pill once a day.

Most drug-drug interaction studies used the twice-daily dose of boosted darunavir. Until more data are available, twice-daily dosing should be considered when darunavir is used with efavirenz, nevirapine, and etravirine in treatment-experienced patients. However, in combination with raltegravir and maraviroc, once-daily dosing is an option. Neither lopinavir/ritonavir nor saquinavir is recommended for use with darunavir because of a significant decrease in darunavir serum concentration that occurs when these drugs are used together.  

In the earlier POWER 1 and 2 trials, 80 patients who were PI-experienced and did not have baseline darunavir resistance-associated mutations were randomised to receive darunavir dosed once daily with ritonavir (800/100 mg) versus darunavir/ritonavir 600/100mg twice daily versus currently available PIs with an optimised background. Similar high responses were achieved in both darunavir dosing arms and were superior to the control arm protease inhibitors.

References

  1. Ortiz R et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1 infected patients at week 48. AIDS 22(12): 1389-1397, 2008