When given with atazanavir with ritonavir or cobicistat for the treatment of HIV-1, the dose of Descovy is 200/10 mg once daily. Co-administration of Descovy with medicinal products that inhibit P-gp and BCRP activity (e.g., cobicistat or ritonavir) are expected to increase the absorption and plasma concentration of tenofovir alafenamide. Coadministration with atazanavir/cobicistat (300/150 mg once daily) increased tenofovir alafenamide AUC and Cmax by 75% and 80%; there was no change in atazanavir AUC, Cmax or Cmin. Coadministration of tenofovir alafenamide (10 mg) and atazanavir/ritonavir (300/100 mg once daily) increased tenofovir alafenamide AUC and Cmax by 91% and 77%, with no change in atazanavir AUC, Cmax or Cmin. 

Based on drug interaction studies conducted with the components of Descovy, no clinically significant drug interactions have been either observed or are expected when Descovy is combined with atazanavir with ritonavir or cobicistat. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and tenofovir alafenamide (10 mg once daily) was studied in 10 subjects. Cmax and AUC of tenofovir alafenamide increased by 77% and 91%; atazanavir Cmax and AUC decreased by 2% and 1% and there was no change in Cmin.

When coadministering tenofovir alafenamide/emtricitabine and Evotaz, the recommended dose of tenofovir alafenamide/emtricitabine is 10/200 mg once daily. Coadministration of tenofovir alafenamide and emtricitabine (10/200 mg, once daily) with atazanavir/cobicistat (300/150 mg, once daily) was studied. Tenofovir alafenamide AUC and Cmax increased by 75% and 80%; tenofovir AUC, Cmax and Cmin increased by 247%, 216% and 273%, respectively. Cobicistat AUC and Cmin increased by 5% and 35%, but Cmax decreased 4%. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Evotaz should not be initiated in patients with creatinine clearance less than 70 ml/min if any coadministered agent (e.g. emtricitabine) requires dose adjustment based on creatinine clearance.

Coadministration of atazanavir/ritonavir (300/100 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg once daily) was studied in 10 healthy volunteers in a crossover study. Tenofovir alafenamide AUC and Cmax increased by 91% and 77%, respectively; tenofovir AUC and Cmax increased by 162% and 112%, respectively. Atazanavir pharmacokinetic parameters were similar to historical controls. The authors hypothesise that the increase in tenofovir alafenamide and tenofovir exposures are due to the intestinal inhibition of P-gp and/or BCRP by ritonavir. Coadministration of atazanavir/ritonavir with tenofovir alafenamide is supported by tenofovir alafenamide safety data.