Table 1.
Concentration of Dapivirine in Plasma, Rectal Fluid, Rectal Tissue, Cervical Fluid, and Cervical Tissue from Samples Collected Before and After the Single- and Multiple-Dose Phases
| Evaluable participants in DPV arm (n = 18) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Plasma LLOQ: 20.0 pg/mL |
Rectal fluid LLOQa: 0.01 (0.01–0.02) ng/mg |
Rectal tissue LLOQa: 0.003 (0.003–0.004) ng/mg |
||||||||||
| Nb | Not validc | BLQ (%)d | Median (IQR) | Nb | Not validc | BLQ (%)d | Median (IQR) | Nb | Not validc | BLQ (%)d | Median (IQR) | |
| Single-dose phase | ||||||||||||
| Predose | 18 | 0 | 18 (100) | BLQ (BLQ–BLQ) | — | — | — | — | — | — | — | — |
| 0.5–1 h | 8 | 0 | 3 (38) | 31.5 (BLQ–54.6) | 8 | 0 | 0 (0) | 30.10 (16.10–43.90) | 8 | 0 | 4 (50) | 0.256 (BLQ–0.666) |
| 2 h | 10 | 0 | 0 (0) | 326.0 (153.0–481.0) | 10 | 2 | 0 (0) | 12.77 (6.06–141.50) | 10 | 0 | 6 (60) | BLQ (BLQ–0.600) |
| 24 h | 18 | 0 | 9 (50) | 20.1 (BLQ–56.6) | 8 | 0 | 6 (75) | BLQ (BLQ–0.02) | 8 | 0 | 8 (100) | BLQ (BLQ–BLQ) |
| 48 h | 18 | 0 | 11 (61) | BLQ (BLQ–27.3) | 4 | 0 | 2 (50) | 0.01 (BLQ–0.04) | 4 | 0 | 4 (100) | BLQ (BLQ–BLQ) |
| 72 h | 18 | 0 | 14 (78) | BLQ (BLQ–BLQ) | 6 | 0 | 5 (83) | BQL (BLQ–BLQ) | 6 | 0 | 6 (100) | BLQ (BLQ–BLQ) |
| Multiple-dose phase | ||||||||||||
| Day 1, predose | 18 | 0 | 18 (100) | BLQ (BLQ–BLQ) | 18 | 1 | 17 (94) | BLQ (BLQ–BLQ) | — | — | — | — |
| Day 2, predose | 18 | 0 | 2 (11) | 67.9 (43.1–111.0) | 18 | 0 | 6 (33) | 0.18 (BLQ–1.91) | — | — | — | — |
| Day 7, predose | 17 | 0 | 0 (0) | 167.0 (136.0–219.0) | — | — | — | — | — | — | — | — |
| 0.5–1 h | 8 | 0 | 0 (0) | 290.5 (147.0–506.5) | 8 | 1 | 0 (0) | 89.70 (44.90–258.0) | 8 | 1 | 6 (75) | BLQ (BLQ–BLQ) |
| 2 h | 9 | 0 | 0 (0) | 403.0 (330.0–493.0) | 9 | 1 | 0 (0) | 26.65 (4.95–278.50) | 8e | 0 | 6 (75) | BLQ (BLQ–0.151) |
| 24 h | 17 | 0 | 0 (0) | 119.0 (86.4–172.0) | 7 | 0 | 3 (43) | 0.01 (BLQ–0.10) | 7 | 0 | 7 (100) | BLQ (BLQ–BLQ) |
| 48 h | 17 | 0 | 0 (0) | 113.0 (69.0–132.0) | 4 | 0 | 3 (75) | BLQ (BLQ–0.04) | 3e | 0 | 3 (100) | BLQ (BLQ–BLQ) |
| 72 h | 17 | 0 | 1 (6) | 80.3 (47.3–129.0) | 6 | 0 | 4 (67) | BLQ (BLQ–0.01) | 6 | 0 | 6 (100) | BLQ (BLQ–BLQ) |
| Evaluable female participants in DPV gel arm (n = 3) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |
Cervical fluid LLOQf: 0.009 (0.004–0.022) ng/mg |
Cervical tissue LLOQf: 0.003 (0.002–0.006) ng/mg |
|
|
|
|
||||||
| Nb | Not validc | BLQ (%)d | Median (IQR) | Nb | Not validc | BLQ (%)d | Median (IQR) | |||||
| Single-dose phase, all times |
7 |
0 |
7 (100) |
BLQ (BLQ–BLQ) |
7 |
0 |
7 (100) |
BLQ (BLQ–BLQ) |
|
|
|
|
| Multiple-dose Phase, all times | 7 | 0 | 7 (100) | BLQ (BLQ–BLQ) | 7 | 0 | 7 (100) | BLQ (BLQ–BLQ) | ||||
Median (IQR) of the weight-normalized LLOQ.
Number of participants providing samples at the corresponding timepoint.
Number of samples for which a valid concentration value could not be obtained, excluded from the calculation of descriptive statistics.
Number of samples with concentration below the LLOQ (percent relative to the total of samples collected at the corresponding timepoint).
One participant, assigned to the 2 and 48 h timepoints, declined to provide samples of rectal tissue at the multiple-dose phase.
Median (range) of the weight-normalized LLOQ.
BLQ, below the lower limit of quantification; DPV, dapivirine; IQR, interquartile range; LLOQ, lower limit of quantification.