Concomitant administration of glecaprevir/pibrentasvir and Kaletra is not recommended due to an increased risk of ALT elevations associated with increased glecaprevir exposure. Serum concentrations may be increased due to P-glycoprotein, BCRP and OATP1B inhibition by lopinavir/ritonavir.

Coadministration is expected to increase concentrations of glecaprevir and pibrentasvir. It is not recommended to co-administer Kaletra and glecaprevir/pibrentasvir.

Coadministration of glecaprevir/pibrentasvir (300/120 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) was studied in 21 HIV- and HCV-negative subjects. When coadministered with glecaprevir/pibrentasvir, Cmax and AUC for lopinavir and ritonavir were similar when compared to lopinavir/ritonavir alone (lopinavir Cmax, AUC and Ctrough increased by 11%, 24% and 47%, respectively; ritonavir Cmax, AUC and Ctrough increased by 17%, 23% and 38%, respectively. Coadministration increased glecaprevir Cmax, AUC and C24 by 2.55-, 4.38- and 18.6-fold, respectively; pibrentasvir Cmax, AUC and C24 increased by 1.4-, 2.56- and 5.24-fold, respectively. The higher exposures of glecaprevir and pibrentasvir associated with lopinavir/ritonavir are not associated with specific dose-limiting adverse events, but due to limited experience with these regimens in HCV/HIV coinfected patients during clinical trials the use of boosted darunavir regimens with glecaprevir/pibrentasvir is not recommended.