ABSTRACT
OBJECTIVE: Within HIV-positive men having sex with men, the epidemic of hepatitis C virus (HCV) is ongoing. Transmission of resistant variants of HCV after failure of treatment with directly acting antivirals (DAA) could be a major threat to the effectivity of therapy. We determined whether HCV-resistant variants to DAAs were prevalent amongst patients with an acute HCV infection diagnosed in 2013 and 2014 in the Netherlands. METHODS: Target enrichment for viral nucleic acid separation and deep sequencing were used to recover whole HCV genomes of 50 patients with an acute HCV infection. The genomes were assembled by de novo assembly and analysed for known DAA resistance mutations. RESULTS: In acute HCV infected treatment-naive patients, the relevant resistance-associated substitutions were Q80K (40%) in NS3/4a, M28V (24%) and Q30H combined with Y93H (2%) in NS5A and M414T (2%) or S556G (2%) in NS5b. Patients whose HCV infection failed to respond to boceprevir, peginterferon and ribavirin therapy developed mutations in NS3 at position T54A and R155K. CONCLUSIONS: Target enrichment and whole genome sequencing were successfully applied directly on clinical samples from patients with an acute HCV infection.
Subject(s)
Genome, Viral , Hepacivirus/genetics , Hepatitis C/epidemiology , Hepatitis C/virology , Sequence Analysis, DNA , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Coinfection , Drug Resistance, Viral , Genotype , HIV Infections , Hepacivirus/drug effects , Hepatitis C/drug therapy , Hepatitis C/transmission , Humans , Microbial Sensitivity Tests , Mutation , Netherlands/epidemiology , Viral Load , Viral Nonstructural Proteins/geneticsABSTRACT
Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.
Subject(s)
Epidemics , HIV Infections/virology , Hepatitis C/epidemiology , Adult , Coinfection/epidemiology , Coinfection/virology , Hepatitis C/virology , Homosexuality, Male , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Population Surveillance , Risk FactorsABSTRACT
Acute hepatitis C virus (HCV) infections are frequently seen worldwide in certain risk groups, with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in the acute phase of the infection. Currently used methods to diagnose acute HCV infection are IgG antibody seroconversion and repeated HCV RNA measurements, although no definitive diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided both advances in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV infection will affect therapeutic regimens for acute HCV infection in the coming years, leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties, together with some future perspectives on acute hepatitis C epidemiology, virology, immunology, and treatment.
