A longitudinal study of 25 members of a cohort of intravenous drug users in San Francisco who were recently infected with hepatitis C (HCV) has found that during an average of ten months’ follow up, the incidence of superinfection with second strains of HCV was almost as high as incidence of new HCV infections in the group as a whole.
Altogether five cohort members were superinfected with second strains, representing an annual incidence of 20%, while the incidence for new infections among the whole cohort was estimated to be 25%.
The study's authors comment that their findings cast doubt on the viability of a vaccine against HCV, a virus even more genetically diverse than HIV.
Eleven of the subjects were female and 14 male, and all were under 30. In the trial report they are identified with their cohort identification number.
Samples were taken at entry to the study and again after an average follow-up time of 316 days. Some intermediate samples were taken from three subjects suspected of superinfection.
A variety of genetic tests were taken to establish the genotype of subjects’ virus and to detect any possible minority species at baseline, to eliminate possible dual infections. The HCV genome was sampled at two different points, one hypervariable and one less so, to establish accurate phylogenetic trees.
Subjects had on average been infected at the start of the study for no more than 160 days, and no subject for more than 388 days.
Two subjects were seronegative for HCV antibodies but positive for HCV RNA when they joined the study, indicating recent infection (less than three months), and four previously uninfected members of the cohort became infected during the follow-up period and therefore joined the study.
HCV infections were of three genotypes: two widely-differing subtypes of genotype 1, labelled 1a and 1b (15 and one initial infections respectively) and genotype 3 (nine initial infections).
The genotyping was able to establish three probable ‘clusters’ of infection between subjects, and the timing of their first positive HCV RNA sample was able to establish the direction of infection.
Subject 31 (a woman) infected subject 5 (a man) with a genotype 3 virus before the start of the study. Subject 2 (a man) infected subject 46 (a woman) with a genotype 1a virus at or around the start of the study.
Subject 23 infected subject 13 with a 1a virus. One of them then went on to superinfect subject 54, who at the start of the study was the only one carrying subtype 1b virus, at least 184 days into the follow-up period. All three were men.
The other superinfected subjects were subject 30, originally infected with a genotype 3 virus but found to also have a genotype 1a virus at the study’s end; subject 32, originally infected with type 1a but superinfected at least 62 days into the follow-up period with a genotype 3 virus; and two subjects, 25 and 59, who were superinfected with a second genotype 1a virus, in the case of subject 59 at least 89 days into the follow-up period.
Superinfection in these two subjects was established when it was found that the genetic distance between different viruses carried by them was 14% and 18% respectively, compared with a difference of 2% in monoinfected subjects.
Superinfection did not appear to be associated with a change in viral load. Viral load in all subjects declined from a median of 800,000 copies/ml at the start of the study to a median of 63,000 copies/ml at the end.
The study authors comment: “The high frequency of HCV superinfections that we detected among young IDUs indicates the ease with which a new viral strain can surmount immune responses directed at the resident strain.
“The result of this natural-history experiment in HCV challenge indicates that successful vaccination against this highly diverse virus may prove to be difficult.”
Herring BL et al. Frequent hepatitis C virus superinfection in injection drug users. J Infect Dis 190: 1396-1402, 2004.