TABLE 3.
ISL susceptibility by multiple cycle assay (100% NHS) and clinical frequency for a panel of HIV-1 variants containing mutations observed in ISL viral selection experimentsa
| HIV-1 variant | IC50 (nM)b | FCc | Frequencyd (total PLWH) | Frequencyd (NRTI-experienced PLWH) |
|---|---|---|---|---|
| WT | 1.06 ± 0.21 (n = 40) | 1.0 | ND | ND |
| M41L | 0.80 ± 0.06 (n = 6) | 0.8 | 8.64 | 23.96 |
| L74I | 0.97 ± 0.09 (n = 12) | 0.9 | 1.40 | 3.99 |
| V90I | 0.93 ± 0.15 (n = 13) | 0.9 | 3.48 | 6.72 |
| A114S | 2.10 ± 0.31 (n = 11) | 2.0 | <0.01e | 0.01e |
| A158T | 0.97 ± 0.12 (n = 9) | 0.9 | 0.19 | 0.37 |
| C162Y | 0.63 ± 0.08 (n = 5) | 0.6 | 2.33 | 2.78 |
| T165A | 0.90 ± 0.13 (n = 6) | 0.8 | 0.08 | 0.17 |
| M184I | 6.56 ± 1.37 (n = 18) | 6.2 | 0.96 | 3.04 |
| M184V | 7.25 ± 1.81 (n = 18) | 6.8 | 19.11 | 56.15 |
| A400T | 0.77 ± 0.12 (n = 4) | 0.7 | 67.30 | 69.28 |
| M41L/A114S | 3.31 ± 0.69 (n = 4) | 3.1 | <0.01f | <0.01f |
| M41L/M184V | 5.98 ± 0.83 (n = 5) | 5.6 | 5.77 | 16.13 |
| L74I/M184I | 4.44 ± 0.73 (n = 5) | 4.2 | 0.03 | 0.11 |
| V90I/M184I | 5.86 ± 1.75 (n = 5) | 5.5 | 0.31 | 1.04 |
| A114S/M184V | 40.14 ± 3.97 (n = 9) | 37.9 | <0.01f | <0.01f |
| C162Y/M184I | 3.87 ± 0.28 (n = 5) | 3.6 | 0.04 | 0.15 |
| C162Y/M184V | 13.33 ± 1.15 (n = 5) | 12.6 | 0.60 | 1.66 |
| T165A/M184I | 7.80 ± 0.95 (n = 5) | 7.4 | <0.01f | <0.01f |
| T165A/M184V | 13.78 ± 2.24 (n = 5) | 13.0 | 0.03 | 0.11 |
| M184V/H221Y | 7.93 ± 0.66 (n = 6) | 7.5 | 1.63 | 5.44 |
| M41L/A114S/M184V | 68.68 ± 5.79 (n = 5) | 64.8 | <0.01f | <0.01f |
| M41L/A114S/M184V/A400T | 62.34 ± 4.56 (n = 4) | 58.8 | Not observed | Not observed |
FC, fold change; HIV-1, human immunodeficiency virus type 1; IC50, half maximal inhibitory concentration; ND, not determined; PLWH, people living with HIV; WT, wild-type.
IC50 is displayed as the geometric mean ± standard deviation.
FC is calculated as (IC50 against mutant isolate)/(IC50 against WT) for each test article.
Frequency of each variant = (number of PLWH with specified substitutions/total number of PLWH with sequence available at the specified residues) × 100. This value was determined without excluding variants with additional substitutions or mixtures at the designated residues using the Stanford HIV Drug Resistance Database (18). The frequency data were calculated based on the database in February 2021.
There were 8 total and 5 NRTI-experienced PLWH with A114S detected.
Variants were present in 1 to 4 individuals within the Stanford HIV Drug Resistance Database out of ~178,000 total or ~43,000 NRTI-experienced PLWH.