Table 4.
Pharmacokinetic interactions with HCV DAAs.
| Drug | Simeprevir† | Daclatasvir‡ | Asunaprevir§ | Beclabuvir¶ | Sofosbuvir ± ledipasvir# | Paritaprevir/ritonavir ombitasvir and dasabuvir †† |
|---|---|---|---|---|---|---|
| Antiretrovirals | ||||||
| ABC | ↔‡‡ | |||||
| ATR | Not recommended ‡‡ | LDV ↓ 34% SOF ↓ 6% TDF ↑ 98%§§ Monitor for tenofovir- associated adverse reactions |
||||
| ATV/r | Not recommended ‡‡ | DCV ↑ 110%¶¶ Reduce dose to 30 mg |
↔‡‡,## | ABT-450 ↑ 94%†††,‡‡‡ Give ATV 300 mg without ritonavir in am |
||
| CPA | LDV ↑ 8% SOF ↑ 10% TDF ↑ 40% Monitor for tenofovir- assocaited adverse reactions |
Not recommended | ||||
| DRV/r | SPV ↑ 159% DRV ↑ 18% RTV ↑ 32% Not recommended §§§ |
SOF ↑ 37% Not clinically relevant ## |
Not recommended ‡‡‡ | |||
| DTG | ↔‡‡ | |||||
| EFV | SPV ↓ 71% Not recommended |
DCV ↓ 32%¶¶¶ Increase dose to 90 mg |
EFV ↓ 10%## (See ATR) | |||
| ENF | ↔### | |||||
| ETR | Not recommended ‡‡ | |||||
| FTC | ↔### | FTC ↑ 5% Not clinically relevant ## |
↔††† | |||
| LPV/r | Not recommended ‡‡ | ABT-450 ↑ 87% (LPV Cmin↑ >200%) Not recommended |
||||
| MVC | ↔### | |||||
| NVP | Not recommended ‡‡ | |||||
| RAL | SPV ↓ 11% RAL ↑ 8% Not clinically relevant ### |
SOF ↓ 8.5% RAL ↓ 16%†††† Not clinically relevant ## |
↔††† No adjustments necessary ‡‡‡ |
|||
| RPV | SPV ↑ 6% RPV ↑ 12% Not clinically relevant ### |
RPV ↑ 6%##,‡‡ Not clinically relevant (warning with tenofovir) |
RPV ↑
150–243% Not recommended |
|||
| TDF | SPV ↓ 14% TDF ↑ 18% Not clinically relevant ### |
DCV ↑ 10% TDF ↑10% Not clinically relevant |
TDF ↑ (see ATR, CPA; caution with boosted regimens-see prescribing information) |
TDF ↑13%††† No adjustments necessary ‡‡‡ |
||
| TPV/r | Not recommended ‡‡ | SOF ↓ Not recommended ‡‡ |
||||
| 3TC | ↔### | ↔‡‡ | ||||
| Non-ARVs | ||||||
| Digoxin | Digoxin ↑ 27%§§§§ Use with caution |
Digoxin ↑ 30%§§§§ Use with caution |
||||
| Midazolam | Midazolam ↓ 46– 50%¶¶¶¶ |
Arrows indicate increased, decreased or unaffected plasma area under the curve (AUC).
Not explicitly studied.
Monitor for tenofovir-associated adverse reactions in patients receiving ledipasvir/sofosbuvir concomitantly with the combination of efavirenz, emtricitabine and TDF [24].
DCV 20 mg once a day (q.d.); showed less than the threefold elevation in systemic exposure predicted by prior studies with potent CYP3A inhibitors [52].
Results from PHOTON-2 show that coinfected patients on these ARVs and SOF plus RBV achieved SVR12 rates of 84–89%. These SVR12 rates were similar to those observed in HCV monoinfection with no subject requiring ARV changes [56].
Initial data from pharmacokinetic studies in the coinfected population reported no significant interactions between the ‘3D’ regimen and these agents. SVR rates for both evaluated arms were high (94% in 12-week arm and 91% in 24-week arm) and consistent with those observed in HCV monoinfected patients. No subject had a confirmed HIV-1 RNA of >400 copies/ml and none required a switch of their antiretroviral therapy regimen due to loss of HIV-1 virologic suppression [19,60].
SPV 50 mg q.d. compared with intake of SPV 150 mg alone [51].
DCV 120 mg q.d.; showed less than the twofold reduction in systemic exposure predicted by prior interaction studies with potent CYP3A inducers [52].
These antiretrovirals (ARVs) were utilized in clinical studies with SPV in coinfected patients without any clinically significant interactions [50].
With LDV alone [42].
With SOF alone [54].
The lowest dose of digoxin should be initially prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical effect. Effects of DCV and ASV inhibition of P-gp do not appear to be additive when given concomitantly [45].
Beclabuvir 150 or 300 mg; resulted in dose-dependent decrease in midazolam exposure and increase in 1’-hydroxymidazolam exposure by 10–22% [49].
ABC: Abacavir; ATR: Atripla (efavirenz/emtricitabine/tenofovir); ATV/r: Atazanavir/ritonavir; CPA: Complera (rilpivirine/emtricitabine/tenofovir); DAA: Direct-acting antiviral; DCV: Daclatasvir; DRV/r: Darunavir/ritonavir; DTG: Dolutegravir; EFV: Efavirenz; ENF: Enfuvirtide; ETR: Etravirine; FTC: Emtricitabine; HCV: Hepatitis C virus; LDV: Ledipasvir; LPV/r: lopinavir/ritonavir; MVC: Maraviroc; NVP: Nevirapine; RAL: Raltegravir; RPV: Rilpivirine; SOF: Sofosbuvir; SPV: Simeprevir; TDF: Tenofovir; TPV/r: Tipranavir/ritonavir; 3TC: Lamivudine; ABT-450/r: Paritaprevir/ritonavir; ABT-267: Ombitasvir; ABT-333: Dasabuvir; 3D: Paritaprevir/ritonavir, ombitasvir, dasabuvir.
Data taken from [45].
Data taken from [49].