Table 1.
Direct Acting Antivirals in 2014: Approved and Investigational
| DAA | Mechanism of action | Application status | Genotype activity | Barrier to resistance |
Dosing | Length of therapy (DAA/PR) |
Antiretroviral considerations |
|---|---|---|---|---|---|---|---|
| Telaprevir | NS3/4A Protease Inhibitor (first generation, first wave) |
FDA approved | GT 1 only | Low | BID or TID | 12/48* weeks | Contraindicated with protease inhibitors and NNRTIs (except atazanavir and efavirenz). Requires increased dosage when coadministered with efavirenz. |
| Boceprevir | NS3/4A Protease Inhibitor (first generation, first wave) |
FDA approved | GT 1 only | Low | TID | 24-44/48* weeks | Contraindicated with protease inhibitors and efavirenz. |
| Sofosbuvir | NS5B RNA Polymerase Inhibitor |
FDA New Drug Application pending approval |
GT 1-6 | High | Daily | 12 weeks | No clinically significant interactions with antiretroviral therapy known. |
| Simeprevir | NS3/4A Protease Inhibitor (first generation, second wave) |
FDA New Drug Application pending approval |
GT 1, 2, 4, 5, and 6 | Low | Daily | 12/24-48 weeks | Concentrations significantly decreased in presence of efavirenz and significantly increased in presence of darunavir/ritonavir. No clinically significant interactions with raltegravir, rilpivirine, and tenofovir. |
| Faldaprevir | NS3/4A Protease Inhibitor (first generation, second wave) |
Awaiting FDA New Drug Application |
GT 1, 2, 4, 5, and 6 | Low | Daily | 12-24/24-48 weeks | Concentrations reduced by efavirenz and increased by boosted protease inhibitors. No clinically significant interactions with raltegravir and maraviroc. |
| Daclatasvir | NS5A Inhibitor | Awaiting FDA New Drug Application |
GT 1-6 | Low | Daily | 12-24 weeks | Concentrations reduced by efavirenz and increased by boosted protease inhibitors. No clinically significant interactions with tenofovir. |
*
There are no published data that support response-guided therapy in HIV-HCV coinfection, although this is an area of current investigation.
DAA Direct acting antiviral, FDA Food and drug administration, GT Genotype, NS Non-structural, NNRTIs Non-nucleoside reverse transcriptase inhibitors