Coadministration with raltegravir (400 mg twice daily) increased raltegravir Cmax, AUC and Cmin by 2.33-, 2.34- and 2.00-fold respectively. The increase in raltegravir exposures may be due to UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. The combination was not linked to any particular safety issues in a limited set of patients treated for 12-24 weeks. No clinically relevant changes in dasabuvir, paritaprevir and ombitasvir exposures (based on comparison with historical data) were observed during co-administration. No dose adjustment is necessary.

No dose adjustments are recommended when ombitasvir, paritaprevir, ritonavir and dasabuvir are co-administered with raltegravir.

Coadministration of raltegravir (400 mg twice daily with 2 NRTIs) and ombitasvir/paritaprevir/ritonavir (25/150/100 mg once daily) with dasabuvir (250 mg twice daily) was studied in 11 HIV/HCV coinfected patients. Raltegravir Cmax and AUC decreased by 32% and 18% after initiation of the HCV therapy, however, confidence intervals were wide and three of the 11 patients had increased raltegravir exposure. Among participants with decreases in raltegravir exposure during HCV therapy, raltegravir Cmax and AUC decreased by 44%and 36%, respectively. Among participants with increasing values during HCV therapy, raltegravir Cmax and AUC increased by 125% and 94%, respectively. Although decreases in raltegravir exposure were observed in the majority of study participants, raltegravir has a wide therapeutic index and these changes were not associated with virologic failure. Comparing ombitasvir, paritaprevir, ritonavir and dasabuvir pharmacokinetics to healthy controls, study participants demonstrated generally lower Cmax and AUC values, but none of the participants experienced HCV virological failure.

Coadministration of ombitasvir/paritaprevir/ritonavir ± dasabuvir with raltegravir (n=42) was studied in a retrospective observational study in co-infected HIV and HCV patients. There was no significant effect on raltegravir Ctrough, however the effect on ombitasvir, paritaprevir, ritonavir or dasabuvir was not studied.

Coadministration of ombitasvir/paritaprevir/r + dasabuvir (25/150/100 + 400 mg, once daily) with raltegravir (400 mg twice daily) was studied in 20 healthy volunteers. (Note, the 400 mg dose of dasabuvir used in this study provides equivalent exposures to that of the 250-mg marketed dose of dasabuvir.) Raltegravir Cmax, AUC, and Ctrough increased by 133%, 134%, 100%, respectively. Cross-study comparisons of geometric mean AUC values indicated that exposures for paritaprevir, ritonavir, ombitasvir, and dasabuvir during coadministration were within the range of AUC values for the 3D regimen alone in historical phase 1 studies. No dose adjustment is required during coadministration of raltegravir with the 3D regimen.