TABLE 2.
Effect of HIV and HCV PIs, cobicistat, and inhibitors of host serine proteases on TAF antiviral activity in primary human CD4+ T cells
| Inhibitor class | Compound (concn tested, μM)a | EC50, nM (fold change)b |
|
|---|---|---|---|
| TAF | TDF | ||
| HIV PI | Darunavir (8.9) | 4.2 ± 0.8 (0.8) | 2.7 ± 1.0 (1.0) |
| Atazanavir (6.3) | 5.4 ± 2.1 (1.0) | 3.0 ± 1.0 (1.1) | |
| HCV PI | Telaprevir (5.2) | 110.5 ± 51.2 (20.9) | 3.3 ± 1.0 (1.2) |
| Boceprevir (3.3) | 14.2 ± 3.9 (2.7) | 2.6 ± 0.4 (0.9) | |
| Simeprevir (13.3) | 5.2 ± 1.5 (1.0) | 3.2 ± 1.6 (1.1) | |
| CYP3A | Cobicistat (2.2) | 4.4 ± 0.5 (0.8) | 3.4 ± 1.5 (1.2) |
| Factor Xa | Apixaban (0.2) | 10.4 ± 1.2 (2.0) | 4.0 ± 0.6 (1.4) |
| Rivaroxaban (0.3) | 7.2 ± 3.0 (1.4) | 4.2 ± 0.4 (1.5) | |
| Thrombin | Argatroban (1.0) | 8.9 ± 4.7 (1.7) | 4.6 ± 0.4 (1.6) |
| Dabigatran (0.4) | 9.1 ± 4.0 (1.7) | 4.2 ± 1.5 (1.5) | |
| DPP4 | Sitagliptin (1.0) | 8.3 ± 6.7 (1.6) | 3.6 ± 0.1 (1.3) |
a
The tested inhibitors were used at concentrations corresponding to their clinical peak plasma levels (Cmax).
b
Baseline TAF and TDF EC50 values (mean ± standard deviation), determined from triplicate infectivity measurements within CD4+ T cell populations from six independent donors, were 5.3 ± 1.2 nM and 2.8 ± 1.1 nM, respectively. The average fold changes in TAF and TDF EC50s were obtained from triplicate measurements in four independent donors after a 1-h pretreatment of infected cells at their clinical Cmax prior to addition of serially diluted TAF or TDF.