Liver disease is a leading cause of death among patients with human immunodeficiency virus type 1 (HIV-1) infection. Coinfection with HIV-1 and hepatitis C virus (HCV) appears to accelerate the course of HCV-associated liver disease and is widespread, particularly among injection-drug users. The effect of HIV-1 coinfection on the course of HCV disease is reduced but not eliminated by antiretroviral therapy.
Adoption of interferon-based HCV treatments has been low among HIV–HCV coinfected patients owing to a high adverse-event burden. Furthermore, the rate of sustained virologic response to interferon–ribavirin is lower among patients with HIV–HCV coinfection than among those with HCV monoinfection. Response rates similar to those in patients with HCV monoinfection were observed among patients receiving peginterferon–ribavirin plus the first-generation HCV protease inhibitors telaprevir or boceprevir, but these regimens were associated with increased rates of adverse events and pharmacokinetic interactions with concomitant antiretroviral drugs.
The development of interferon-free, oral regimens of direct-acting antiviral agents represents an important opportunity for improved HCV treatment in patients with HIV–HCV coinfection. Such regimens have shown superior efficacy and an improved side-effect profile with shorter treatment durations than those with interferon-based therapy.
Daclatasvir inhibits HCV nonstructural protein 5A (NS5A) and sofosbuvir inhibits the HCV RNA polymerase (nonstructural protein 5B [NS5B]), two proteins that play key roles in the replication of HCV RNA. The two drugs are administered orally once daily and in combination have pangenotypic anti-HCV activity. The combination of daclatasvir and sofosbuvir has been associated with high rates of sustained virologic response and a favorable side-effect profile when administered for 12 weeks or 24 weeks, with or without ribavirin, to patients monoinfected with HCV genotype 1, 2, or 3. Furthermore, clinical data for sofosbuvir plus ledipasvir, another NS5A inhibitor, in patients with genotype 1 monoinfection and without cirrhosis suggested that previously untreated patients receiving 8 weeks of treatment would have a rate of sustained virologic response similar to that of patients receiving 12 weeks of treatment.
Daclatasvir and sofosbuvir have limited pharmacokinetic interactions with antiretroviral drugs, and dose adjustments for daclatasvir in patients receiving moderate antiretroviral inducers or strong inhibitors of cytochrome P-450 3A4 are straightforward. Thus, this combination may be valuable for treating patients with HIV–HCV coinfection. In the ALLY-2 trial, we evaluated daclatasvir plus sofosbuvir for 12 weeks or 8 weeks in HIV–HCV coinfected patients without previous HCV treatment and for 12 weeks in previously treated patients. View article