Extended Data Table 4.
Pharmakokinetics of 3BNC117 based on a 56-day period post infusion. Estimation of PK parameters retrieved from study participants (ID) up to 8 weeks post 3BNC117 infusion. 3BNC117 was administered at 1, 3, 10, and 30 mg/kg in uninfected (Negative) and HIV-1-infected (Positive) individuals. 3BNC117 serum concentrations were determined by ELISA or TZM.bl assay (see Methods). PK-parameters were obtained by performing a non-compartmental analysis (NCA) using WinNonlin 6.3. T1/2 was estimated using values between Lambda upper/lower. n.d., PK parameters were not determined because of insufficient data or an extrapolated AUC_inf that exceeded 25%. Values in red indicate extrapolated AUC_inf >10%.*, Days post infusion of 3BNC117.
| ID | HIV-1/ART | 3BNC117 (mg/kg) |
Method | Cmax (μg/ml) |
adjusted R-squared |
Estimated T1/2 (days) |
Lambda (lower)* |
Lambda (upper)* |
AUC (INF_pred) |
Tlast* | Clast (μg/ml) |
AUC_% Extrap_pred |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1A1 | Negative | 1 | ELISA | 27.4 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| TZM.bl | 27.4 | 0.936 | 21.32 | 14 | 42 | 184.0 | 42 | 1.2 | 19.2 | |||
| 1A2 | Negative | 1 | ELISA | 18.8 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| TZM.bl | 27.8 | 0.893 | 12.89 | 7 | 42 | 181.7 | 42 | 1.0 | 9.0 | |||
| 1A3 | Negative | 1 | ELISA | 11.2 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| TZM.bl | 23.5 | 0.976 | 10.38 | 4 | 28 | 138.0 | 28 | 1.3 | 14.0 | |||
| 2A1 | Positive/Off | 1 | ELISA | 15.7 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| 2A3 | Positive/Off | 1 | ELISA | 22.7 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| 2A4 | Positive/Off | 1 | ELISA | 33.8 | n.d. | n.d. | – | – | n.d. | – | – | n.d. |
| TZM.bl | 15.6 | n.d. | n.d. | – | – | n.d. | – | – | n.d. | |||
|
| ||||||||||||
| 1B1 | Negative | 3 | ELISA | 89.9 | 0.985 | 19.64 | 7 | 56 | 685.2 | 56 | 3.1 | 12.1 |
| TZM.bl | 70.9 | 0.881 | 24.30 | 7 | 56 | 483.7 | 56 | 2.7 | 17.9 | |||
| 1B2 | Negative | 3 | ELISA | 90.1 | 0.878 | 12.91 | 7 | 42 | 523.5 | 42 | 2.2 | 8.8 |
| TZM.bl | 116.0 | 0.936 | 10.04 | 7 | 42 | 481.2 | 42 | 1.4 | 4.6 | |||
| 1B3 | Negative | 3 | ELISA | 243.4 | 0.954 | 21.54 | 14 | 56 | 1017.3 | 56 | 4.2 | 12.1 |
| TZM.bl | 74.5 | 0.954 | 21.70 | 7 | 56 | 706.6 | 56 | 3.9 | 15.6 | |||
| 2B1 | Positive/Off | 3 | ELISA | 90.8 | 0.942 | 9.60 | 4 | 21 | 219.4 | 21 | 2.8 | 19.2 |
| TZM.bl | 57.4 | 0.994 | 10.28 | 7 | 28 | 245.9 | 28 | 1.9 | 12.1 | |||
| 2B2 | Positive/On | 3 | ELISA | 97.6 | 0.928 | 8.74 | 7 | 21 | 200.7 | 21 | 2.5 | 16.5 |
| 2B3 | Positive/Off | 3 | ELISA | 60.0 | 0.981 | 9.08 | 4 | 21 | 251.2 | 21 | 3.5 | 17.0 |
| TZM.bl | 32.6 | 0.994 | 9.19 | 4 | 28 | 129.8 | 28 | 1.0 | 10.1 | |||
|
| ||||||||||||
| 1C1 | Negative | 10 | ELISA | 347.8 | 0.942 | 16.33 | 7 | 56 | 1667.9 | 56 | 5.9 | 7.5 |
| TZM.bl | 281.8 | 0.964 | 15.79 | 7 | 56 | 1598.9 | 56 | 5.6 | 7.3 | |||
| 1C3 | Negative | 10 | ELISA | 308.9 | 0.860 | 29.01 | 7 | 56 | 2529.4 | 56 | 15.8 | 23.5 |
| TZM.bl | 244.7 | 0.700 | 26.59 | 14 | 56 | 2228.5 | 56 | 13.1 | 19.3 | |||
| 1C4 | Negative | 10 | ELISA | 180.6 | 0.835 | 10.73 | 7 | 42 | 859.1 | 42 | 4.0 | 5.5 |
| TZM.bl | 230.7 | 0.990 | 10.56 | 14 | 56 | 1022.0 | 56 | 1.4 | 2.2 | |||
| 2C2 | Positive/On | 10 | ELISA | 326.8 | 0.866 | 10.87 | 7 | 42 | 904.5 | 42 | 2.7 | 5.6 |
| 2C4 | Positive/Off | 10 | ELISA | 178.2 | 0.944 | 6.92 | 4 | 28 | 550.2 | 28 | 2.8 | 5.1 |
| TZM.bl | 193.0 | 0.979 | 6.14 | 4 | 28 | 417.9 | 28 | 1.8 | 3.4 | |||
| 2C5 | Positive/Off | 10 | ELISA | 201.1 | 0.997 | 6.60 | 7 | 28 | 592.6 | 28 | 2.6 | 4.1 |
| TZM.bl | 174.4 | 0.994 | 6.50 | 7 | 28 | 431.2 | 28 | 1.8 | 3.7 | |||
|
| ||||||||||||
| 1E2 | Negative | 30 | ELISA | 360.8 | 0.930 | 14.48 | 7 | 56 | 4259.4 | 56 | 13.6 | 5.9 |
| TZM.bl | 1166.3 | 0.978 | 16.19 | 14 | 56 | 5901.2 | 56 | 16.1 | 6.2 | |||
| 1E3 | Negative | 30 | ELISA | 361.8 | 0.990 | 16.26 | 7 | 56 | 3177.5 | 56 | 11.7 | 8.2 |
| TZM.bl | 606.2 | 0.989 | 17.85 | 7 | 56 | 3422.2 | 56 | 12.3 | 9.3 | |||
| 1E5 | Negative | 30 | ELISA | 765.0 | 0.992 | 14.15 | 4 | 56 | 5874.2 | 56 | 16.3 | 5.7 |
| TZM.bl | 939.6 | 0.959 | 15.22 | 14 | 56 | 6424.5 | 56 | 19.1 | 6.1 | |||
| 2C1 | Positive/Off | 30 | ELISA | 410.2 | 0.991 | 5.80 | 7 | 28 | 1707.8 | 28 | 5.1 | 2.6 |
| TZM.bl | 717.4 | 0.993 | 5.99 | 7 | 42 | 2186.4 | 42 | 1.6 | 0.6 | |||
| 2D1 | Positive/Off | 30 | ELISA | 976.4 | 0.996 | 6.86 | 7 | 42 | 2494.9 | 42 | 3.4 | 1.3 |
| TZM.bl | 849.3 | 0.990 | 8.83 | 7 | 56 | 1825.5 | 56 | 1.1 | 0.8 | |||
| 2D3 | Positive/Off | 30 | ELISA | 571.0 | 0.962 | 13.39 | 7 | 56 | 3616.5 | 56 | 9.9 | 4.8 |
| TZM.bl | 953.7 | 0.993 | 11.23 | 7 | 42 | 4346.2 | 42 | 16.0 | 6.0 | |||
| 2E1 | Positive/Off | 30 | ELISA | 712.4 | 0.970 | 11.14 | 14 | 56 | 3028.5 | 56 | 4.6 | 2.3 |
| 2E2 | Positive/Off | 30 | ELISA | 789.4 | 0.920 | 11.14 | 7 | 56 | 3596.1 | 56 | 6.7 | 2.4 |
| 2E3 | Positive/Off | 30 | ELISA | 559.6 | 0.821 | 8.54 | 7 | 28 | 2495.6 | 28 | 13.7 | 8.4 |