Table 3.
Susceptibility to Nevirapine, Efavirenz, and Etravirine of Participant-Derived Recombinant Viruses With or Without N348I
| Nevirapine |
Efavirenz |
Etravirine |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Mutations | IC50, Mean ± SD, µmol/L | Failure vs Pretherapya (P) | 348I vs 348Nb (P) | IC50, Mean± SD, nmol/L | Failure vs Pretherapya (P) | 348I vs 348Nb (P) | IC50, Mean ± SD, nmol/L | Failure vs Pretherapya (P) | 348I vs 348Nb (P) |
| Participant 1 | |||||||||
| Pretherapy | 0.032 ± 0.006 | 0.87 ± 0.16 | 1.3 ± 0.2 | ||||||
| K103N/M184V | 16 ± 7.4 | 500 (<.01) | 8.9 (<.01) | 13 ± 6.7 | 15 (.03) | 56 (.01) | 3.4 ± 0.5 | 2.60 (<.01) | 1.9 (.03) |
| K103N/M184V/N348I | 142 ± 44 | 4438 (<.01) | 725 ± 189 | 833 (<.01) | 6.6 ± 2.0 | 5.10 (<.01) | |||
| Participant 6 | |||||||||
| Pretherapy | 0.018 ± 0.002 | 0.46 ± 0.14 | 0.6 ± 0.1 | ||||||
| Y181C/M184V | 98 ± 3.3 | 5444 (<.01) | >2.0 (<.01) | 3.8 ± 1.2 | 8.3 (.02) | 9.6 (<.01) | 6.1 ± 2.5 | 10.0 (.01) | 4.7 (.02) |
| Y181C/M184V/N348I | >200c | >11111 (<.01) | 37 ± 7.7 | 80 (<.01) | 28 ± 3.2 | 47.0 (<.01) | |||
| Participant 7 | |||||||||
| Pretherapy | 0.091 ± 0.019 | 1.28 ± 0.30 | 1.5 ± 0.4 | ||||||
| V106A/M184V | 11 ± 2.1 | 121 (<.01) | 13 (.01) | 2.4 ± 0.4 | 2.0 (<.01) | 6.5 (.01) | 0.53 ± 0.15 | 0.35 (.01) | 3.2 (<.01) |
| V106A/M184V/N348I | 148 ± 45 | 1626 (<.01) | 16 ± 2.6 | 13 (<.01) | 1.7 ± 0.3 | 1.13 (.74) | |||
| Participant 11 | |||||||||
| Pretherapy | 0.149 ± 0.008 | 1.94 ± 0.25 | 1.1 ± 0.1 | ||||||
| K103N/Y181C/M184V | >200c | >1342 (<.01) | … | 22 ± 14 | 11 (<.01) | 5.4 (.05) | 0.93 ± 0.32 | 0.85 (.37) | 2.1 (<.01) |
| K103N/Y181C/M184V/N348I | >200c | >1342 (<.01) | 114 ± 15 | 59 (<.01) | 2.0 ± 0.8 | 1.80 (.04) | |||
| Participant 12 | |||||||||
| Pretherapy | 0.050 ± 0.006 | 0.48 ± 0.12 | 0.5 ± 0.1 | ||||||
| K103N/M184V/G190A | 109 ± 35 | 2180 (<.01) | >1.8 (.06) | 321 ± 251 | 669 (<.01) | 14 (.02) | 0.35 ± 0.19 | 0.70 (.14) | 2.1 (<.01) |
| K103N/M184V/G190A/N348I | >200c | >4000 (<.01) | 4583 ± 2129 | 9548 (<.01) | 0.74 ± 0.26 | 1.48 (.10) | |||
| Participant 13 | |||||||||
| Pretherapy | 1.0 ± 0.4 | 7.87 ± 1.84 | 0.6 ± 0.1 | ||||||
| M184V/G190A | >200c | >200 (<.01) | … | 354 ± 73 | 45 (<.01) | 4.3 (<.01) | 1.1 ± 0.3 | 1.80 (.04) | 1.5 (.02) |
| M184V/G190A/N348I | >200c | >200 (<.01) | 1530 ± 268 | 194 (<.01) | 1.6 ± 0.6 | 2.70 (.02) | |||
Abbreviations: IC50, concentration required to inhibit viral replication by 50%; SD, standard deviation.
a Mean fold change in IC50 of recombinant virus with participant-derived reverse-transcriptase at virologic failure versus before therapy (pretherapy).
b Mean fold change in IC50 of recombinant virus with 348I vs 348N.
c Nevirapine cytotoxicity was observed at >200 μmol/L.