TABLE 1.
Susceptibilities of HIV-1 and HIV-2 RT mutants to MK-8591
| HIV clonea | Genotypeb | EC50 (nM)c | No.d | Fold changee |
|---|---|---|---|---|
| HIV-1NL4-3 | Wild type | 2.0 ± 0.62 | 10 | |
| M184V | 18 ± 6.8 | 4 | 9 | |
| HIV-2ROD9 | Wild type | 0.42 ± 0.12 | 14 | |
| K65R | 0.17 ± 0.03 | 3 | 0.4 | |
| Q151M | 0.38 ± 0.15 | 3 | 1 | |
| M184V | 11 ± 6.4 | 6 | 26 | |
| K65R+Q151M | 0.20 ± 0.06 | 3 | 0.5 | |
| K65R+M184V | 8.0 ± 2.7 | 3 | 19 | |
| Q151M+M184V | 5.9 ± 3.6 | 5 | 14 | |
| K65R+Q151M+M184V | 6.2 ± 2.0 | 3 | 15 | |
| K65R+K70R+Q151M+M184V | 7.0 ± 2.5 | 3 | 17 | |
| K65R+Y115F+Q151M+M184V | 5.3 ± 3.3 | 5 | 13 | |
| HIV-2ROD9-4.7a | K65R+N69S+V111I+Q151M+M184V | 5.4 ± 0.7 | 3 | 13 |
Viruses produced from full-length plasmids pNL4-3, pROD9, and patient-derived clone pROD9-4.7a.
Amino acid changes listed for HIV-1NL4-3 and HIV-2ROD9 were engineered by site-directed mutagenesis. Changes listed for HIV-2ROD9-4.7a were encoded by a pol gene segment that was PCR amplified from an HIV-2-infected patient (32).
EC50, 50% effective concentrations measured in the MAGIC-5A single-cycle assay. Values shown in bold are significantly different from the corresponding wild-type value (P < 0.05; analysis of variance of log10-transformed EC50s with Sidak's posttest).
Number of independent dose-response assays performed for each strain.
EC50 for the mutant divided by the EC50 for the corresponding wild-type clone (wild-type HIV-2ROD9 for the patient-derived strain).