Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta-analysis.
OBJECTIVE
Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b infection. A definite conclusion about efficacy and safety of DCV + ASV in patients with HCV genotype 1b is not available. A meta-analysis was conducted to evaluate outcomes of all-oral treatment with DCV + ASV in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks and adverse effects after the end of treatment.


METHODS
PUBMED, MEDLINE, and EMBASE databases were searched in May 2016. The data were analyzed with Review Manager 5.3.


RESULTS
Nine trials (n = 1690) met entry criteria. SVR12was achieved by 89.9% of treatment-naïve patients, 84.7% of interferon-ineligible/intolerant patients, and 81.9% of nonresponder patients. Moreover, 89.0% of interferon-ineligible/intolerant patients and 83.1% of nonresponder patients achieved SVR24. Baseline characteristics, including gender, race, advanced age, non-CC IL28B genotype, and cirrhosis, did not appear to impact SVR rates. However, the rate of SVR12in all patients with viral load < 8 × 105was higher than that of all those with viral load ≥ 8 × 105(151/162 vs 625/753). Moreover, pre-existing nonstructural protein 5A resistance-associated variants (RAVs) were associated with virological failure during DCV + ASV therapy, resulting in the emergence of multiple RAVs. Treatment with DCV + ASV was well tolerated, with low incidences of serious adverse effects, discontinuations, and grade 3 or 4 laboratory abnormalities in all patients.


CONCLUSIONS
Daclatasvir plus asunaprevir provides a highly effective and well-tolerated treatment option for patients with HCV genotype 1b. However, patients with nonstructural protein 5A RAVs at baseline should be assessed to optimize more potent direct antiviral agent therapies.
Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of Medicine, Xi'an, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
Hui-Lian
HL
Wang
School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, China.
Xi
X
Lu
Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of Medicine, Xi'an, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
Xudong
X
Yang
2nd Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Nan
N
Xu
D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D016206:Databases, Bibliographic; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007546:Isoquinolines / Q000008:administration & dosage*; D011759:Pyrrolidines; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir; C571889:asunaprevir
asunaprevir; daclatasvir; hepatitis C virus; hepatitis C virus genotype 1; hepatitis C virus genotype 1b