Table 7.
Significant pharmacokinetic and pharmacodynamic predictors of virologic response with darunavir-based therapy
| Predictor | Outcome | Notes |
|---|---|---|
| Baseline virtual phenotypic susceptibility | ||
| VL <50 copies/mL | POWER 1, 2, 331 | |
| Susceptible (S) (IC50 FC < 10) | 50% | |
| Partial susceptibility (P) (IC50 FC 10–40) | 25% | |
| Resistant (R) (IC50 FC > 40) | 13% | |
| VL < 200 copies/mL | PREDZISTA32 | |
| S: IC50 FC <10 | 68% | |
| I: IC50 FC 10–40 | 46% | |
| R: IC50 FC > 40 | 20% | |
| Baseline darunavir RAMs | ||
| Number | VL <50 copies/mL | POWER 1, 2, 331 |
| 0 | 65% | |
| 1 | 50% | |
| 2 | 40% | |
| 3 | 20% | |
| ≥ 4 | 10% | |
| Number | VL <200 copies/mL | PREDZISTA32 |
| <4 | 89% | Identified darunavir RAMs differ from IAS, Stanford and ANRS mutations |
| 4–5 | 52% | |
| >5 | 0% | |
| Activity of background antiretroviral drugs | ||
| GSS | VL <50 copies/mL | POWER 1, 219 |
| 0 | 20% | GSS calculated as the sum of each drug’s score: |
| 1 | 50% | 0 for resistant by genotype, 1 for susceptible |
| ≥ | 56% | |
| GSS | VL <200 copies/mL | PREDZISTA32 |
| 0 0.5 | 20% | GSS calculated as the sum of each drug’s score: 0 for resistant by genotype, 0.5 for possibly resistant, 1 for susceptible |
| 1–1.5 | 59% | |
| 2–3 | 70% | |
| Inhibitory quotients | ||
| vIQ | ΔVL > −1 log10 | POWER 1, 238 |
| ≤ 0.1 | 32% | |
| 0.1 to ≤ 0.4 | 61% | |
| 0.4 to ≤ 1.4 | 80% | |
| >1.4 | 84% | |
| vIQ | VL <50 copies/mL | Darunavir salvage therapy in PI-experienced adults39 |
| ≤ 1.5 | 29% | |
| >1.5 | 71% | |
| gIQ | VL <200 copies/mL | PREDZISTA32 |
| ≤ 1.8 | 0% | |
| >1.8 | 55% | |
Notes and Abbreviations: IC50, 50% inhibitory concentration in vitro; FC, fold change in IC50 relative to wild-type IC50; VL, viral load; RAMs, resistance associated mutations; GSS, genotypic sensitivity score, which quantifies the activity of the additional antiretroviral drugs in the regimen based on genotype; vIQ, virtual phenotypic inhibitory quotient, which is the ratio of the trough darunavir concentration to the IC50 of the dominant strains as measured by virtual phenotype; gIQ, genotypic inhibitory quotient which is the ratio of the trough darunavir concentration to the number of darunavir RAMs in the dominant viral strains.