Table 1.
An overview of DCV DDIs with HCV regimen partners and antiretroviral agents
| Drug/dose | Concomitant medication | DCV | |||||
|---|---|---|---|---|---|---|---|
| C max GMR (90% CI) | AUC GMR (90% CI) | AUC | C max GMR (90% CI) | AUC GMR (90% CI) | AUC | Dose adjustment | |
| HCV DAAs | |||||||
| Sofosbuvir (400 mg QD)a | 0.8 (0.77, 0.90) | 1.0 (0.95, 1.08) | ↔ | 0.88 (0.78, 0.99) | 0.95 (0.82, 1.10) | ↔ | None |
| Asunaprevir (200 mg BID during co-administration)b | 0.58 (0.45, 0.76) | 0.87 (0.73, 1.04) | ↔ | 1.07 (0.97, 1.18) | 1.20 (1.11, 1.30) | ↔ | None |
| Simeprevir (150 mg QD) | 1.39 (1.27, 1.52) | 1.44 (1.32, 1.56) | ↑ | 1.50 (1.39, 1.62) | 1.96 (1.84, 2.10) | ↑ | None |
| HIV integrase inhibitors | |||||||
| Dolutegravir (50 mg QD) | 1.29 (1.07, 1.57) | 1.33 (1.11, 1.59) | ↑ | 1.03 (0.84, 1.25) | 0.98 (0.83, 1.15) | ↔ | None |
| Raltegravir (400 mg BID)c | 1.04 (0.87, 1.23) | 0.94 (0.78, 1.14) | ↔ | Comparable to historic controls | ↔ | None | |
| Elvitegravir (unboosted) | NS | NS | ↔ | NS | NS | ↔ | None |
| HIV fusion inhibitors/CCR5 antagonists | |||||||
| Enfuvirtide/maraviroc | NS | NS | ↔ | NS | NS | ↔ | None |
| HIV NRTIs | |||||||
| Tenofovir (300 mg QD) | 0.95 (0.89, 1.02) | 1.10 (1.05, 1.15) | ↔ | 1.06 (0.98, 1.15) | 1.10 (1.01, 1.21) | ↔ | None |
| Lamivudine, zidovudine, emtricitabine, abacavir, didanosine, stavudine | NS | NS | ↔ | NS | NS | ↔ | None |
| HIV NNRTIs | |||||||
| Efavirenz (600 mg QD)d | NS | NS | NS | 0.83 (0.76, 0.92) | 0.68 (0.60, 0.78) | ↓ | 90 mg |
| Etravirine/neviripine | NS | NS | NS | NS | NS | ↓ | NR:90 mge |
| Rilpivirine | NS | NS | ↔ | NS | NS | ↔ | None |
| HIV protease inhibitors | |||||||
| Atazanavir/r (300/100 mg QD)e | NS | NS | NS | 1.35 (1.24, 1.47) | 2.10 (1.95, 2.26) | ↑ | 30 mg |
| Darunavir/rf | 0.97 (0.80, 1.17) | 0.90 (0.73, 1.11) | ↔ | 0.77 (0.70, 0.85) | 1.41 (1.32, 1.50) | ↔ | None |
| Lopinavir/rf | 1.22 (1.06, 1.41) | 1.15 (0.77, 1.72) | ↔ | 0.67 (0.61, 0.74) | 1.15 (1.07, 1.24) | ↔ | None |
| HIV PK-boosted fixed-dose combinations | |||||||
| Stribild | NS | NS | ↔ | NS | NS | ↑ | 30 mg |
All interaction studies used daclatasvir 60 mg QD, unless otherwise stated (daclatasvir AUC GMR [90% CI] dose normalized to 60 mg QD)
AUC area under curve, BID twice daily, CI confidence interval, C max maximal concentration, DAAs direct-acting antivirals, DCV daclatasvir, DDIs drug–drug interactions, GMR geometric mean ratio, HCV hepatitis C virus, HIV human immunodeficiency virus, NNRTIs non-nucleoside reverse transcriptase inhibitors, NRTIs nucleoside/nucleotide reverse transcriptase inhibitors, NR not recommended, NS not studied (effects on C max, AUC, and associated dose modifications are predicted), PK pharmacokinetic, QD once daily, ↓ exposure decreased, ↑ exposure increased, ↔ exposure unchanged (refers to clinically significant change)
aPlasma levels of GS-331007 (major circulating metabolite) were assessed
bDaclatasvir/asunaprevir 60 mg QD/600 mg BID for 7 days alone then 30 mg QD/200 mg BID during co-administration
cDCV 60 mg + ASV 100 mg BID (18/20 patients received rilpivirine/tenofovir/emtricitabine)
dDaclatasvir 60 or 120 mg QD
eCombination is not recommended in the EU label (lack of data), but dose modification (90 mg/day) is recommended in the US prescribing information
fDaclatasvir 20 mg QD
gDaclatasvir 30 mg QD