Table 1.
Mean IC50 ± SD, fold change values for doravirine and other licensed NNRTIs against infectious clones harbouring NNRTI resistance-associated mutations (RAMs) and levels of doravirine activity predicted by the Stanford HIVdb and ANRS prediction algorithms
| Virus ID | NNRTI RAMs | NRTI RAMs | Other mutations | Mean doravirine IC50 ± SD (nM) | Fold change (FC) |
Predicted doravirine activityd |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Doravirineb | Nevirapinec | Efavirenzc | Etravirinec | Rilpivirinec | Stanford HIVdb | ANRS | |||||
| 12225a | E138G, H221Y, F227L, M230L | M41L, L210W, T215Y | K122E, D177E, I178L, R211K, V245M, I293V | >100 | >100 | >200 | 15 | 21 | 18 | R | R |
| 12227a | K101P, K103N | M41L, T215Y | A98S, K102Q, D123E, K166R, D177E, D192N, R211K, V245K, K277R, R284K, T286A, E297K | 0.4 ± 0.1 | 0.4 | >200 | >200 | 5.8 | 92 | S | S |
| 12229a | L100I, K103N, H221Y | M41L, L74V, M184V, T215Y | R83K, D177E, T200A, R211Q, K281R, R284K, I293V, E297A | 4.8 ± 0.3 | 4.0 | >200 | >200 | 6.8 | 6.3 | I | R |
| 12231a | K103N, V179F, Y181C | M41L, T215F | K49R, K82R, A98S, D177E, G196E, Q207K, R211A, L228R, A272P, I293V, K311R | 26.5 ± 14.4 | 22.1 | >200 | 90 | 8.8 | 2.3 | I | R |
| 12233a | K101E, Y181V | K70R, M184V, T215F | T27S, E28K, K32E, V60I, T69N, R83K, V179I, T200A, Q207D, L228R, V245E, T286A, E297K | 3.3 ± 0.5 | 2.8 | >200 | 2.1 | 27 | 24 | I | I |
| 12235a | A98G, K101E, Y181C, G190A | M41L, E44D, D67N, T69D, L74I, L210W, T215Y | T39E, V118I, K122E, I135T, G196E, E203K, R211K, A272S, V276T, K277R, Q278E, L283I, I293V, E297K | 38.2 ± 5.8 | 31.8 | >200 | >200 | 15 | 22 | R | R |
| 12237a | V106I, Y181C, G190A, H221Y | none | V35I, S68G, A98S, D121E, K122E, I135V, R211K, F214L, V245E, D250E, A272P, E297K | >100 | >100 | >200 | 26 | 6 | 3.5 | R | R |
| 12239a | A98G, K101E, E138K, Y181C | M41L, T215D | K122E, I135T, S162Y, T200A, L210F, P243T, V245E, D250E, A272P, I274V, Q278H, K281R, T286A, A288S, K311R | 17.0 ± 4.0 | 14.2 | >200 | 3.6 | 10 | 9.2 | I | R |
| 12241a | K101E, E138G, G190S | none | V35M, R211K, V245E, S251I | 3.8 ± 1.4 | 3.1 | >200 | >200 | 3.2 | 2.6 | I | R |
| 12243a | L100I, V179D, M230L | M41L, D67G, L74I, M184V, T215Y | V35I, K103R, K122E, I202V, R211K, T240K | 7.5 ± 0.6 | 6.2 | >200 | >200 | 95 | 13 | R | R |
| NL4-3/103N | K103N | 2.0 ± 1.2 | 1.4 | NA | NA | NA | NA | S | S | ||
| NL4-3/181C | Y181C | 2.6 ± 1.1 | 1.8 | NA | NA | NA | NA | S | S | ||
| NL4-3/ 103N/181C | K103N, Y181C | 6.9 ± 2.8 | 4.9 | NA | NA | NA | NA | I | R | ||
| NL4-3/230L | M230L | 10.6 ± 4.7 | 7.6 | NA | NA | NA | NA | R | R | ||
NA, not available.
a
NIH AIDS Reagent Program catalogue number.
b
Doravirine FC values calculated according to the NL4-3 strain IC50 value of 1.4 ± 0.7 nM.
c
FC values determined through the Phenosense Assay.16
d
The HIVdb five-level grading was collapsed to three levels as indicated by the HIValg release notes at https://hivdb.stanford.edu/page/release-notes/. S, susceptible; I, intermediate resistance; R, high-level resistance.