Navarro J, et al. – Researchers here focused on profile of once–daily darunavir/cobicistat fixed–dose combination for the treatment of HIV/AIDS. Observations revealed that cobicistat had no inducer effect on metabolic pathways and showed much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 seemed to be less affected by cobicistat, and thus fewer drug–drug interactions were expected.

• Rezolsta (darunavir/cobicistat) was identified as the first fixed–dose combination containing a protease inhibitor approved for HIV treatment.
• This coformulation seemed to include darunavir, a protease inhibitor that proved efficacious and safe in naïve and treatment–experienced patients, and cobicistat, the new pharmacokinetic enhancer that was expected to replace ritonavir.
• Studies involving healthy volunteers indicated bioequivalence between ritonavir and cobicistat as darunavir boosters.
• Furthermore, phase III studies including naïve and pretreated patients without darunavir–associated resistance mutations indicated comparable efficacy and safety profile of darunavir/cobicistat to historical data of darunavir/ritonavir 800/100 mg once–daily formulation.
• Scarce and mild adverse events with darunavir/cobicistat were evident, these included basically skin reactions and gastrointestinal disturbances.
• Despite small increases in plasma creatinine in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, there appeared no alteration regarding actual glomerular filtrate rate.