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.