Drugs

Fenton, Caroline; Perry, Caroline

doi: 10.2165/00003495-200767180-00010pmid: 18062724

▲ Darunavir (TMC114) is a nonpeptidic peptidomimetic HIV protease inhibitor (PI), with a high binding affinity and a close fit within the substrate envelope. ▲ Darunavir shows potent in vitro activity against a broad range of clinical isolates of HIV type 1 (HIV-1), including those with decreased susceptibility to most available PIs. ▲ The bioavailability of oral darunavir is increased when it is coadministered with ritonavir. Thus, darunavir must be administered in combination with low-dose (100mg) ritonavir. ▲ In the POWER 1 and POWER 2 trials, two 144-week randomised phase IIb trials, a reduction in plasma HIV-1 RNA levels of ≥1 log 10 copies/mL (primary endpoint) occurred in 77% and 62% of treatment-experienced recipients of darunavir plus ritonavir (darunavir/ritonavir) 600mg/100mg twice daily (in combination with an optimised background regimen) [vs 25% and 14% of control PI (CPI) recipients; p < 0.001] at week 24. Results are from primary analyses (n = 301 and 201). ▲ In a pooled subgroup analysis of data from the POWER 1 and 2 trials, reductions in HIV-1 RNA levels of ≥1 log 10 copies/mL were achieved in 61% of patients treated with darunavir/ritonavir 600mg/ 100mg twice daily versus 15% of CPI recipients (p < 0.0001) at week 48. ▲ Darunavir/ritonavir 600mg/100mg was generally well tolerated in the POWER 1 and 2 trials, with a tolerability profile similar to that of comparator CPIs.