TABLE 6.
Lersivirine-resistant virus carrying multiple RT mutations and inhibited by other NNRTIsa
| Virus stockb | Passage no.c | RT mutations | Fold change in EC50 from that for drug-sensitive reference virus of indicated drugd |
||||
|---|---|---|---|---|---|---|---|
| Lersivirine | EFV | DLV | NVP | ZDV | |||
| Passaged control | 11 | 0.6 | 0.3 | 0.3 | 0.2 | 0.2 | |
| Lersivirine+ | 9 (a) | V108I, E138K | 14.0 | 1.0 | 1.5 | 0.9 | 0.4 |
| 11 (a) | V108I, E138K, F227F/L | 143 | 3.2 | 1.8 | 12.2 | 0.6 | |
| 11 (b) | V108I, H221Y, F227F/L, M230 M/I | 60.5 | 2.4 | 0.2 | 6.4 | 0.1 | |
| Efavirenz+ | 11 | L100I, K103Q, H221H/Y | 5.0 | 16.3 | 16.4 | 1.0 | 0.1 |
Mutations were identified in the GeneSeq HIV (PR/RT) assay at Monogram Biosciences. Susceptibilities to lersivirine, efavirenz (EFV), delavirdine (DLV), and nevirapine (NVP) were determined in Monogram Bioscience's PhenoSense assay. The NRTI zidovudine (ZDV) was used as a control. No time points before passage 9 were investigated.
Passaged control, virus passaged in the absence of compound; lersivirine+, virus passaged in the presence of increasing concentrations of lersivirine; efavirenz+, virus passaged in the presence of increasing concentrations of efavirenz.
The two different pathways to resistance are labeled a and b (in parentheses).
The drug-sensitive virus CNDO was used as the reference virus for estimation of fold change in EC50.