High incidence of hepatitis C virus reinfection in a cohort of injecting drug users

Abstract

An estimated 170 million people worldwide carry the hepatitis C virus (HCV), and in more developed countries the prevalence and incidence of HCV is particularly high among injecting drug users (IDUs). Spontaneous clearance of HCV infection and reinfection is well recognized but the level of protection against further infection conferred by HCV infection and clearance remains uncertain. We conducted a prospective study of HCV infection in IDUs recruited in Melbourne, Australia, using a much shorter median testing interval than in previous studies. Incidences of naive infection and reinfection were calculated by the person-year method and Cox proportional hazards regression used to adjust for covariates. A significantly higher HCV incidence rate was measured in previously infected IDUs (46.8% per year) compared with HCV-naive IDUs (15.5% per year). The hazard ratio for previously infected IDUs compared to HCV-naive IDUs, after adjustment for time-dependent covariates, was 2.54 (95% confidence interval, 1.11-5.78, P > ͦzͦ < 0.05). Viral persistence after reinfection appeared similar to that following naive infection. Conclusion: Our data suggest that HCV infection in IDUs is more likely following prior infection and clearance than in HCV-naive individuals, implying no increased immunity against further infection. This result has important implications for the future development of an HCV vaccine. T he hepatitis C virus (HCV) infects an estimated 170 million people worldwide, and is a significant cause of morbidity and mortality due to cirrhosis and hepatocellular carcinoma. 1 Injecting drug users (IDUs) are the population subgroup at greatest risk of HCV infection in more developed countries, with prevalence rates of 45% or greater per year 2,3 and incidence rates of 25% per year or higher being common. 4,5 HCV differs from the hepatitis B virus and many other infectious viral agents in that infection and the generation of an immune response does not necessarily protect an individual from HCV reinfection or superinfection. Whether infection with HCV and subsequent clearance is even partially protective against further infection is yet to be definitively resolved.In 2002, Mehta et al. 6 reported that previously infected IDUs were significantly less likely to be reinfected, even after accounting for risk behavior. Further reports supported this finding: Grebely et al. 7 reported a significantly lower incidence of HCV reinfection in IDUs than in naive individuals; and Dove et al. 8 detected no reinfections in a small group of ongoing IDUs with previous HCV clearance. A retrospective study by Micallef et al. 9 reported the incidence of HCV reinfection in IDUs was higher than naive infection-31 out of 100 person-years (PYs) (95% confidence interval [CI], 17-62) compared to 17 out of 100 PYs (95% CI, 14-2) although with adjustment for HCV risk behavior variables, the incidence ratio was only marginally greater and was not statistically significant (incidence rate ratio, 1.11; P ϭ 0.8).The importance of the reinfection is...

Origin and Evolution of the Unique Hepatitis C Virus Circulating Recombinant Form 2k/1b

“…Although both viruses are associated with chronic infections, unlike HIV, HCV can be spontaneously cleared by the host. This may explain in part the differences in the number of recombinants between HIV and HCV, where partial protective immunity against the latter reduces that chance of in vivo recombination of HCV strains (1,43,69). However, the high rate of mixed infections observed suggests that this is likely at best to play a minor role in HCV recombination.…”

Optimal targeting of Hepatitis C virus treatment among injecting drug users to those not enrolled in methadone maintenance programs

“…The number of new infections per year is therefore given by so that per year. There is debate about the rate of reinfection in those that have previously cleared infection with estimates ranging from 2% to 47% per year (Aitken et al, 2008a;Backmund et al, 2004;Grebely et al, 2006). We assume a reinfection rate, of 5% per year thus but acknowledge that new research suggests it is higher than this.…”

A quasi-markov model for transmission and disease elimination: Hepatitis C among people who inject drugs

“…And, P11=P44, P12=P42, P13=P43, P17=P27=P37=P47= P57=P67=μ and for k=1,…, (27, Some research has found that following spontaneous clearance of an acute infection a proportion of individuals may have protective immunity to re-infection; however, findings regarding a conferring of a protective immunity are equivocal [40][41][42][43]. In order to capture the possibility of some level of a protective immunity, a corresponding state (z) was included in the natural history model with a low transition probability (0.25) [19].…”