Pharmacokinetic interaction between nevirapine and darunavir with low‐dose ritonavir in HIV‐1‐infected patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The protease inhibitor (PI) darunavir with low-dose ritonavir (DRV/r) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) are used in combination with other antiretroviral agents and they may be co-administered for the treatment of HIV-1 infection. • There is the potential for a pharmacokinetic interaction between NVP and DRV/r, since these drugs use similar metabolic pathways. WHAT THIS STUDY ADDS • This study assesses for the first time the extent of the drug–drug interaction between NVP and DRV/r in the relevant population of HIV-1-infected patients. AIM To investigate the pharmacokinetic interaction between darunavir/ritonavir (DRV/r) and nevirapine (NVP) in 19 HIV-infected patients. METHODS An open-label, randomized, crossover study. Patients received Treatment A [NVP 200 mg b.i.d. plus ≥2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] and Treatment B [A plus DRV/r 300/100 mg b.i.d. (DRV oral solution)] or Treatment B2 [A plus DRV/r 400/100 mg b.i.d. (DRV tablet)] in two 14-day sessions. RESULTS Mean NVP AUC12h increased by 27% [least square means ratio 1.27 (95% confidence interval 1.02, 1.58)]. Mean DRV and ritonavir exposures were similar to historical data. Co-administration was well tolerated. CONCLUSIONS DRV/r and NVP have no clinically relevant interaction. No dose adjustments are required.