Incident Hepatitis C Virus Genotype Distribution and Multiple Infection in Australian Prisons

Abstract

Hepatitis C virus (HCV) is a highly diverse pathogen that is classified into seven distinct genotypes. Simultaneous or sequential reinfection with multiple HCV genotypes is recognized in high-risk populations, such as injecting drug users (IDUs). Multiple infection is of clinical concern as different genotypes have various sensitivities to current antiviral therapies. Therefore, a better understanding of the frequency of multiple infection and of the genotypes currently being transmitted is clinically relevant. An Australian cohort of IDUs (n ‫؍‬ 123), identified with primary incident infection, was followed for multiple infection by regular HCV RNA testing between 2005 and 2013. A total of 354 samples were tested. Sequencing of primary incident infections revealed that genotype 3a was the most common circulating genotype, followed by genotype 1a. Examination of longitudinally collected samples identified complex patterns of multiple infection, including reinfection and superinfection. In those with multiple infection, there was no apparent evidence of homotypic immunity conferring protection against reinfection of the same subtype. This study revealed frequent multiple infection in a high-risk prisoner cohort, illustrating the complex nature of HCV infection and reinfection and highlighting the need for pan-genotypic antiviral therapies.

A latent class approach to identify multi‐risk profiles associated with phylogenetic clustering of recent hepatitis C virus infection in Australia and New Zealand from 2004 to 2015

“…The association between HCV subtype 3a and phylogenetic clustering, with all clusters containing individuals infected over multiple years, is consistent with other reports of an increased proportion of incident HCV infection as a result of subtype 3a, compared to 1a, particularly among HIV‐negative PWID , a smaller population of infected people, and more recent introduction of subtype 3a to Australia, compared to 1a . This phenomenon has also been observed in countries such as Scotland , Germany , England , Canada and the United States .…”

Understanding the Determinants of BnAb Induction in Acute HCV Infection

“…A total of 590 subjects from 34 correctional centres were enrolled between 2005 and 2012 in HITS-p, and 268 subjects were recruited from three urban Sydney regions (southwest, inner metropolitan, and western Sydney) between 2008 and 2014 in HITS-c. Details of these cohorts have been previously reported [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. All serum was tested for anti-HCV antibodies using the Abbott ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CIA) (Abbott Diagnostics, Chicago, IL, USA) and HCV RNA quantification was performed using either the VERSANT HCV RNA Qualitative Transcription Mediated Amplification (TMA) assay (Bayer Diagnostics, Emeryville, CA, USA) or the COBAS AmpliPrep/ COBAS TaqMan HCV assay (Roche, Basel, Switzerland), as previously described [ 37 ].…”

Envelope-Specific IgG3 and IgG1 Responses Are Associated with Clearance of Acute Hepatitis C Virus Infection

“…These 14 subjects were described extensively elsewhere [19]. In brief, the 14 subjects had a primary HCV infection with the most prevalent Australian strains, including genotypes 1a (n = 5), 1b (n = 3), 3a (n = 4), and 2b (n = 2) [13]. The estimated days post infection (DPI) of the initial infection time point ranged from four to 45 days (median 30).…”

“…Following acute infection, approximately 75% of people fail to clear the virus, resulting in chronic hepatitis [5][6][7]. While direct-acting antiviral (DAAs) treatments are decreasing the number of people living with HCV, control remains challenging globally due to the limitations in health infrastructure and high drug cost for treatment of the marginalised population affected, in addition to high rates of re-infection [8][9][10][11][12][13]. As HCV can be cleared naturally in a subset of individuals (~25%), and as subsequent re-infections are characterised by higher clearance rates (up to~80%), it is reasonable to hypothesise that a vaccine could be designed to elicit effective immune responses that confer protection [14,15].…”