Evaluation of pharmacokinetic interactions between long-acting HIV-1 fusion inhibitor albuvirtide and lopinavir/ritonavir, in HIV-infected subjects, combined with clinical study and simulation results.

1. A clinical study to assess the interactions between albuvirtide (320 mg) and lopinavir/ ritonavir (400/100 mg) was conducted in 10 HIV-1-infected subjects. Because albuvirtide requires a long period to achieve steady state, and extended monotherapy may lead to early resistance, it is unethical to take albuvirtide alone to achieve steady state. Therefore, a population pharmacokinetic model was developed to predict steady-state concentration-time curve of solely administered albuvirtide. 2. When albuvirtide and lopinavir/ritonavir were co-administered, the plasma concentration of albuvirtide when the infusion ended (C-end) increased by about 34%, but the geometric mean ratios and 90% confidence intervals (90% CIs) of AUC((0-t)) [1.09 (0.96-1.24)] and C-trough [1.00 (0.83-1.20)] were within the range of 0.8-1.25. For lopinavir, the ratios (90% CIs) of AUC((0-t)), C-max and C-trough were 0.63 (0.49-0.82), 0.67 (0.53-0.86) and 0.65 (0.46-0.91); for ritonavir, those ratios (90% CIs) were 0.62 (0.42-0.91), 0.61 (0.38-0.99) and 0.72 (0.40-1.26), respectively. 3. Co-administration of albuvirtide with lopinavir/ritonavir has little effect on albuvirtide exposure, but it decreases the plasma exposures of lopinavir/ritonavir. However, the drug-drug interactions may not reduce the effectiveness of this co-therapy, the trough concentration of lopinavir may be sufficient and this combination could achieve similar clinical efficacy with marketed drugs. So, a phase 3 clinical trial without dose adjustment is underway to validate their effectiveness and safety.