Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.

BACKGROUND

Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection.

PURPOSE

To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection.

DATA SOURCES

MEDLINE and EMBASE from inception through 1 November 2016.

STUDY SELECTION

42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs.

DATA EXTRACTION

Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently.

DATA SYNTHESIS

Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without.

LIMITATIONS

Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling.

CONCLUSION

Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis.

PRIMARY FUNDING SOURCE

Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).