Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C

Marco, A; Esteban, Juan Ignacio; Solé, Concepció; Silva, A. da; Ortiz, Jordi; Roget, Mercè; Sarriera, C; Teixidó, Núria; Guerrero, Rafael; Caylà, Joan A.

doi:10.1016/j.jhep.2013.03.008

Cited by 60 publications

(55 citation statements)

References 40 publications

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“…The risk of HCV reinfection is significantly higher in people treated for chronic HCV infection who report ongoing risk behaviour, with reinfection incidence in those reporting injecting drug use post-treatment ranging between 0.0 and 33.0 per 100 py [12,49,50,56,60,[62][63][64]. In a metaanalysis examining reinfection incidence among PWUD (recent and lifetime), overall reinfection incidence was 2.4 per 100 py (95% CI 0.9, 6.1), rising to 6.4 per 100 py (95% CI 2.5, 16.7) in those who reported injecting drug use post-SVR [12].…”

Section: Hcv Reinfection Among People Who Inject Drugsmentioning

confidence: 99%

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

Martinello¹,

Hajarizadeh²,

Grebely³

et al. 2017

Curr HIV/AIDS Rep

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Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID. However, the incidence of reinfection following interferon-based treatment for chronic HCV is low among PWID. Reinfection rates in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence reported in some cohorts. Mathematical modelling suggests that substantial reductions in HCV incidence and prevalence could be achieved with targeted DAA therapy among those at the highest risk of ongoing transmission. This review will summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV coinfection, discuss the individual- and population-level impact of DAA treatment scale-up and reinfection, and highlight ongoing and future research questions in expanding HCV care and treatment to those populations at high risk of ongoing HCV transmission.

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Section: Hcv Reinfection Among People Who Inject Drugsmentioning

confidence: 99%

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

Martinello¹,

Hajarizadeh²,

Grebely³

et al. 2017

Curr HIV/AIDS Rep

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“…Nevertheless, new infections are on the rise among young IDUs in developed countries and along drug-trafficking routes (2, 5, 6). Because DAA treatment is prohibitively expensive and does not prevent reinfection (7,8), an effective vaccine is essential for management of the global HCV epidemic (9-11).Despite the significant public health burden, no effective prophylactic vaccine against HCV has been developed. High genetic variability of the virus is a major barrier, particularly in the E1 and E2 envelope glycoproteins that are the primary neutralizing antibody (NAb) targets.…”

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confidence: 99%

mentioning

confidence: 99%

Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen

Kong

Lee

Kadam

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

108

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Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including the conserved CD81 receptor-binding site (CD81bs) that is a key target of broadly neutralizing antibodies (bNAbs). Unfortunately, immunization with recombinant E2 and E1E2 rarely elicits sufficient levels of bNAbs for protection. To understand the challenges for eliciting bNAb responses against the CD81bs, we investigated the E2 CD81bs by electron microscopy (EM), hydrogen-deuterium exchange (HDX), molecular dynamics (MD), and calorimetry. By EM, we observed that HCV1, a bNAb recognizing the N-terminal region of the CD81bs, bound a soluble E2 core construct from multiple angles of approach, suggesting components of the CD81bs are flexible. HDX of multiple E2 constructs consistently indicated the entire CD81bs was flexible relative to the rest of the E2 protein, which was further confirmed by MD simulations. However, E2 has a high melting temperature of 84.8°C, which is more akin to proteins from thermophilic organisms. Thus, recombinant E2 is a highly stable protein overall, but with an exceptionally flexible CD81bs. Such flexibility may promote induction of nonneutralizing antibodies over bNAbs to E2 CD81bs, underscoring the necessity of rigidifying this antigenic region as a target for rational vaccine design.hepatitis C virus | E2 | CD81-binding site | conformational flexibility | protein dynamics H epatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma, infecting more than 2% of the world's population (1). HCV infection is highly prevalent in developing countries and among marginalized populations, such as injection drug users (IDUs) and prisoners in developed countries (2). Effective direct-acting antiviral (DAA) drugs have been developed recently to curb the advance of HCV (3, 4). Nevertheless, new infections are on the rise among young IDUs in developed countries and along drug-trafficking routes (2, 5, 6). Because DAA treatment is prohibitively expensive and does not prevent reinfection (7,8), an effective vaccine is essential for management of the global HCV epidemic (9-11).Despite the significant public health burden, no effective prophylactic vaccine against HCV has been developed. High genetic variability of the virus is a major barrier, particularly in the E1 and E2 envelope glycoproteins that are the primary neutralizing antibody (NAb) targets. E2, the receptor-binding protein, mediates cell entry by interacting with the tetraspanin CD81 and several other cell surface molecules (12, 13). The crystal structure of the E2 core domain (E2c) consists of a central β-sandwich flanked by "front" and "back" layers (14) (Fig. 1). The CD81-binding site (CD81bs) has been mapped by mutagenesis and electron microscopy (EM) to various elements: a conserved N-terminal...

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“…Risk of HCV reinfection has certainly been demonstrated to be far higher, by thirteen-fold, among people who report actively injecting drugs post-SVR when compared with those who do not (Marco et al, 2013). Individuals found to have been hospitalised for either an injection indicative or alcohol-related cause prior to therapy, being 30% of our cohort, were at significantly increased risk of being admitted or died post-therapy or an opiate/injection-related cause.…”

Section: Discussionmentioning

confidence: 81%

“…There have been a few small studies examining engagement in injection drug use post-HCV antiviral treatment induced SVR, and these have relied on participation and accurate self-report by PWID, and have varied in respect of recruitment setting; thus, rates of continued injection drug use ranged considerably from 12-100% post-SVR (Marco et al, 2013;Page et al, 2009). Results obtained from our study were derived from a large anonymous record-linkage exercise of routine administrative data on all PWID undergoing therapy, thereby increasing cohort size and avoiding participation bias.…”

Section: Discussionmentioning

confidence: 99%

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection

Valerio

Goldberg

Lewsey

et al. 2015

Drug and Alcohol Dependence

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Background: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principle objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). Methods: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record-linkage techniques. Our primary outcome variable was any hospitalisation or death which was indicative of injecting drugs post-SVR. Results: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.6% (95% CI, 8.8-12.8) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.1 per year (95% CI, 1.0-1.2), having a pre-SVR acute alcohol-related hospital episode: AHR:1.8 (95% CI, 1.3 -2.6), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.6 (95% CI, 1.9 -3.7). Conclusion: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant number of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and potential increased risk of reinfection.Pg|2

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Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C

Cited by 60 publications

References 40 publications

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection

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