Taking it

The 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. Its use is licensed for antiretroviral-experienced patients only, but it is being considered for use in those who are treatment-naive.

In the U.S., the same dosing is advised for treatment-experienced patients, but darunavir is also licensed for use in treatment-naive patients. It was approved for twice-daily dosing, but in late 2008, it use was also approved for once-daily dosing, using two 400mg tablets taken with 100mg ritonavir in combination with other antiretroviral drugs. 

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 had a significantly increased likelihood of achieving undetectable viral load on the boosted darunavir arm of the study.^[1]

Most drug-drug interaction studies used the twice-daily dose of boosted darunavir. Until more data is 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 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.^[2]