TABLE 3.
In vitro antiviral activities of TMC278, EFV, ETR, and NVP against 55 SDMs of HIV-1/HXB2 harboring one, two, or three NNRTI RAMs
| NNRTI RAM(s) | Median FC (Q1-Q3)a in the antiviral activity of: |
|||
|---|---|---|---|---|
| TMC278 | EFV | ETR | NVP | |
| V090I | 1.7 (1.4-1.9) (n = 4) | 1.6 (1.4-1.8) (n = 4) | 1.5 (1.4-1.6) (n = 4) | 4.4 (3.4-5.1) (n = 4) |
| L100I | 0.9 (0.5-1.1) (n = 73) | 20.3 (15.5-28.9) (n = 106) | 1.3 (1.0-1.8) (n = 107) | 7.3 (4.7-10.1) (n = 43) |
| K101E | 2.4 (2.0-4.7) (n = 9) | 3.8 (2.7-4.2) (n = 10) | 2.7 (1.5-4.2) (n = 10) | ND |
| K101P | 51.7 (34.7-64.1) (n = 48) | 72.3 (39.0-96.3) (n = 45) | 5.3 (4.6-6.4) (n = 48) | >166.1 (108.9-244.5) (n = 3) |
| K101Q | 1.6 (0.9-2.2) (n = 8) | 2.4 (1.7-3.5) (n = 8) | 1.4 (1.1-2.5) (n = 8) | 2.5 (1.9-3.6) (n = 5) |
| K103N | 0.9 (0.6-1.2) (n = 72) | 32.5 (23.9-43.0) (n = 113) | 0.9 (0.7-1.1) (n = 110) | >42.1 (33.5-54) (n = 51) |
| K103S | 1.6 (1-2) (n = 4) | 4.8 (3.8-6.7) (n = 3) | 0.8 (0.8-1.1) (n = 4) | 59.4 (35.9-83.0) (n = 2) |
| V106A | 0.6 (0.5-0.9) (n = 6) | 2.0 (1.5-2.8) (n = 4) | 0.5 (0.5-0.6) (n = 6) | 49.0 (45.3-81.7) (n = 3) |
| V106M | 0.9 (0.7-1.5) (n = 7) | 2.6 (1.3-3.7) (n = 8) | 0.9 (0.6-1.0) (n = 6) | 6.3 (6.2-10.4) (n = 5) |
| V108I | 0.7 (0.6-1.0) (n = 4) | 1.5 (1.2-1.9) (n = 5) | 0.7 (0.7-0.9) (n = 5) | 3.1 (2.5-3.9) (n = 4) |
| E138A | 2.5 (2.3-2.6) (n = 4) | 1.6 (1.4-2.2) (n = 4) | 2.9 (2.6-3.1) (n = 4) | 2.3 (2.1-3.0) (n = 4) |
| E138G | 1.6 (1.4-2.2) (n = 4) | 0.9 (0.8-1.3) (n = 4) | 2.4 (1.6-3.3) (n = 4) | 2.8 (2.5-2.9) (n = 3) |
| E138K | 2.8 (1.7-3.9) (n = 10) | 2.0 (1.4-2.3) (n = 10) | 2.6 (2.0-4.1) (n = 12) | 1.1 (1.1-1.3) (n = 5) |
| E138Q | 2.7 (2.1-3.9) (n = 7) | 3.4 (2.8-5.6) (n = 8) | 3.0 (2.5-3.7) (n = 7) | 5.1 (3.9-6) (n = 6) |
| E138R | 3.3 (2.9-3.6) (n = 4) | 2.2 (2.0-2.5) (n = 4) | 3.6 (3.2-4.2) (n = 4) | 4.4 (4.1-4.7) (n = 4) |
| E138S | 2.7 (2.5-2.8) (n = 4) | 1.4 (1.1-1.7) (n = 4) | 2.8 (2.1-3.5) (n = 4) | 3.8 (2.0-5.9) (n = 4) |
| V179D | 1.7 (1.1-2.4) (n = 6) | 2.7 (2.5-2.9) (n = 6) | 1.9 (1.4-2.5) (n = 6) | 4.6 (3.7-4.9) (n = 3) |
| V179E | 1.2 (0.7-1.9) (n = 7) | 5.7 (4.0-7.6) (n = 9) | 1.3 (1.2-3.1) (n = 9) | 2.1 (1.3-3.2) (n = 4) |
| V179F | <0.1 (0.1-0.1) (n = 5) | <0.4 (0.2-0.6) (n = 6) | <0.2 (0.1-0.2) (n = 5) | 0.6 (0.5-1.1) (n = 3) |
| V179T | 1.5 (1.5-1.7) (n = 3) | 1.0 (0.9-1.0) (n = 3) | 0.7 (0.7-0.8) (n = 3) | 0.8 (n = 1) |
| Y181C | 2.7 (1.9-3.6) (n = 151) | 2.1 (1.3-3.0) (n = 197) | 4.0 (3.2-5.4) (n = 191) | >43.0 (34.7-76.7) (n = 60) |
| Y181I | 15.3 (12.9-16.8) (n = 3) | 1.6 (1.3-1.9) (n = 4) | 12.5 (10.7-13.2) (n = 3) | >65.7 (60.6-71.5) (n = 3) |
| Y181V | 12.2 (10.8-15.2) (n = 4) | 3.0 (2.3-3.7) (n = 4) | 15.1 (14.2-20.7) (n = 3) | 2,155.9 (n = 1) |
| Y188L | 2.8 (2.1-4.1) (n = 71) | 42.6 (31.3-56.5) (n = 106) | 1.1 (0.9-1.4) (n = 110) | >42.1 (33.1-65.4) (n = 45) |
| G190A | 1.1 (0.8-1.2) (n = 12) | 8.1 (6.3-10.1) (n = 17) | 1.1 (0.8-1.4) (n = 14) | >86.6 (49.6-92) (n = 11) |
| G190S | 0.2 (0.2-0.4) (n = 7) | 94.8 (73.4-131) (n = 8) | 0.2 (0.2-0.3) (n = 8) | 96.9 (54.2-149.1) (n = 4) |
| H221Y | 1.8 (1.3-2.2) (n = 4) | 1.6 (1.3-1.9) (n = 4) | 1.6 (1.1-2.2) (n = 4) | 4.3 (3.7-4.6) (n = 4) |
| M230I | 2.7 (2.5-3.7) (n = 3) | 5.0 (4.6-5.9) (n = 10) | 3.5 (3-4.1) (n = 9) | 13.6 (10.8-18.6) (n = 8) |
| M230L | 3.4 (2.6-4) (n = 4) | 5.9 (3.9-11.1) (n = 9) | 3.6 (2.6-5) (n = 8) | 20.4 (16.8-21.3) (n = 7) |
| M230V | 2.1 (1.5-3.5) (n = 4) | 1.1 (1-1.3) (n = 11) | 0.8 (0.8-1) (n = 8) | 1.4 (1.2-1.7) (n = 8) |
| M236L | 1.1 (1-1.3) (n = 4) | 1.0 (0.6-1.7) (n = 4) | 1.2 (1.0-1.4) (n = 4) | 3.4 (n = 1) |
| L100I, K101E | 2.1 (1.4-2.7) (n = 4) | 49.1 (41.3-50.4) (n = 3) | 0.9 (0.9-1.0) (n = 4) | 18.1 (12.9-24.5) (n = 4) |
| L100I, K103N | 7.0 (4.7-9.7) (n = 138) | >575.8 (56-1,172.2) (n = 149) | 4.0 (2.9-5.3) (n = 178) | >42.5 (33.9-66.8) (n = 48) |
| K101E, K103N | 2.0 (1.2-3.2) (n = 71) | 56.4 (39-86.3) (n = 149) | 1.8 (1.2-2.7) (n = 152) | >41.6 (29.9-59.3) (n = 85) |
| K103N, F227L | 0.5 (0.4-0.6) (n = 3) | 8.9 (7.1-16.2) (n = 3) | 0.5 (0.4-0.6) (n = 3) | 141.1 (109.0-173.1) (n = 2) |
| K103N, V108I | 0.5 (0.5-0.8) (n = 3) | 96.0 (71.1-107.8) (n = 4) | 0.7 (0.6-0.7) (n = 4) | >205.2 (136.7-237.8) (n = 3) |
| K103N, Y181C | 3.5 (2.1-4.8) (n = 246) | 36.5 (25.2-50.7) (n = 420) | 4.1 (2.8-5.5) (n = 426) | >41.8 (29.6-60.6) (n = 128) |
| K103N, Y181I | 94.9 (80.0-117.5) (n = 3) | 6.4 (5.5-7.5) (n = 3) | 16.1 (13.5-21.8) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| E138K, M230L | 22.6 (20.8-24.0) (n = 3) | 18.7 (17.9-22.4) (n = 3) | 19.3 (17.5-26.3) (n = 3) | >63.7 (61.9-70.5) (n = 6) |
| V179D, Y181C | 6.0 (3.9-6.1) (n = 3) | 9.3 (9.2-9.7) (n = 3) | 10.8 (8.6-11.6) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| V179E, Y181C | 6.8 (6.0-7.9) (n = 3) | 13.1 (10.9-14.6) (n = 3) | 30.6 (24.3-36.9) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| V179F, Y181C | 8.7 (6.0-12.2) (n = 79) | 4.6 (3.6-7.5) (n = 76) | 158.9 (113.6-211.6) (n = 79) | >358.3 (267.4-459.3) (n = 7) |
| V179F, Y181I | 11.4 (10.3-27.4) (n = 3) | 1.0 (1.0-1.1) (n = 3) | 122.8 (101.4-146.5) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| V179I, Y181C | 3.7 (3.2-4.0) (n = 3) | 1.3 (1.3-2) (n = 3) | 4.6 (4.3-12.8) (n = 3) | 139.9 (107.2-172.5) (n = 2) |
| Y181C, F227C | 23.6 (17.3-24.7) (n = 3) | 12.1 (11.5-13.5) (n = 4) | 25.3 (18.6-31.5) (n = 3) | >77.3 (71.5-77.4) (n = 3) |
| Y181C, G190S | 3.4 (3.3-4.3) (n = 3) | 486.0 (363.8-604.7) (n = 3) | 20.4 (17.0-26.8) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| Y181C, Y188L | 30.2 (25.9-37.9) (n = 3) | 237.5 (178.8-280.2) (n = 4) | 6.0 (3.7-10.3) (n = 4) | >157.7 (134.0-181.5) (n = 2) |
| L100I, K103N, E138G | 33.2 (23.6-62.7) (n = 6) | 1,695.3 (1,453.9-1,796.3) (n = 6) | 20.8 (10.9-24.3) (n = 5) | >58.1 (50.4-65.7) (n = 7) |
| L100I, K103N, T386A | 22.8 (16.5-27.5) (n = 3) | 10,866.5 (8,349.2-12,035.2) (n = 3) | 12.2 (10.2-15.7) (n = 3) | >51.6 (n = 1) |
| L100I, K103N, V179L | 46.1 (42.1-63.1) (n = 3) | 5,660.6 (5,405.2-6,002.4) (n = 3) | 13.4 (13.1-15.9) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
| L100I, K103N, Y181C | 80.8 (66.0-109.4) (n = 7) | 1,812.0 (1,496.9-2,110.8) (n = 5) | 58.1 (34.8-73.2) (n = 7) | 468.1 (395.5-540.8) (n = 2) |
| L100I, V179I, Y181C | 15.2 (9.1-22.1) (n = 4) | 16.9 (14.6-17.2) (n = 4) | 34.1 (27.0-42.6) (n = 4) | >205.2 (128.4-267.8) (n = 3) |
| K101P, K103N, V108I | >162.1 (115.8-314.9) (n = 3) | 12,931.1 (11,343.6-13,462.3) (n = 3) | 18.4 (17.3-19.7) (n = 3) | >51.6 (n = 1) |
| K103N, V179I, Y181C | 10.5 (8.2-14.1) (n = 9) | 16.7 (12.6-27.3) (n = 8) | 14.5 (10.4-17.2) (n = 8) | >429.9 (252.5-445.1) (n = 7) |
| V179F, Y181C, F227C | 553.8 (386.7-578.5) (n = 3) | 25.7 (22.5-57.7) (n = 3) | 638.6 (559.5-763.1) (n = 3) | >71.5 (68.6-74.4) (n = 2) |
a
Fold changes (FCs) were calculated as the ratio between the 50% effective concentration of the compound for the HIV-1 SDM and that obtained in the same experiment with HIV-1/IIIB. Q1-Q3, first- to third-quartile values; n, number of experiments; ND, not determined.