Coadministration with atazanavir alone increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%, respectively by inhibition of UGT1A1 and CYP3A. When compared to historical controls, there was no effect on atazanavir exposure. Coadministration with atazanavir/ritonavir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%, respectively. There was no effect on the exposure of atazanavir or ritonavir. No dosage adjustment is necessary. Dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

Coadministration of atazanavir alone (400 mg once daily) and dolutegravir (30 mg once daily) to 12 subjects increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) to 12 subjects increased dolutegravir Cmax and AUC by 34% and 62% and increased Ctrough by 2.21-fold. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir.

Coadministration of dolutegravir (30 mg once daily) and atazanavir alone (400 mg once daily) or atazanavir/ritonavir (300/100 mg once daily) was studied in two groups of HIV-negative subjects (n=12 per group). Coadministration with atazanavir alone increased dolutegravir AUC, Cmax and Ctrough by 91%, 50% and 180%. Coadministration with atazanavir/ritonavir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%. These combinations were well tolerated. The authors recommend no dose adjustment when dolutegravir is coadministered with atazanavir alone or atazanavir/ritonavir. Note, this study was performed with a dose of dolutegravir lower than the licensed one.