Background:  The rise in the incidence of acute hepatitis C virus (HCV) infection in HIV⁺ men who have sex with men (MSM) has been well documented. Where individuals clear HCV, associated immunological responses do not provide complete protection from HCV re-infection. We report a group of acutely co-infected MSM who presented with HC viraemia after sustained virological response (SVR) following initial infection. We hypothesised that HC viremia subsequent to SVR was likely to be due to re-infection, following further sexual exposure, rather than late relapse.

Methods:  Databases at both Chelsea and Westminster and Royal Free Hospitals were interrogated to reveal individuals with confirmed HC viremia following SVR to initial HCV infection. SVR was defined as undetectable HCV polymerase chain reaction (PCR) for >6 months either in those who spontaneously cleared infection or following completion of pegylated interferon (PEG-IFN)/ribavarin (RBV). Viral RNA was extracted from paired stored sera. The E1/E2 region, including HVR-1, was amplified by RT-PCR and sequenced. Using PAUP software, a phylogenetic tree was constructed from the paired sequences, facilitating genotypic comparison between the patients’ viruses and unrelated Genebank E1/E2 sequences. Sexually transmitted infection diagnoses during the HCV SVR period were recorded.

Results:  Of 211 co-infected individuals, 16 had ≥2 episodes of HCV infection, the second episode detected following an elevation of alanine aminotransferase (ALT). All were MSM, mean length of HIV infection was 4 years (1 to 17), with a mean age at first HCV infection of 38 years (26 to 51). Mean length of SVR was 20 months (6 to 36); 11 were on HAART and all 16 received PEG-IFN/RBV following their first infection. From 8 individuals, we obtained paired samples that were amplifiable. Phylogenetic analysis revealed 2 individuals with closely related sequences indicative of late relapse. The remaining 6 had divergent, paired sequences likely to represent re-infection with a different strain. HCV genotypes seen in these 6 were the same as the initial infection. All but 2 individuals had ≥1 concurrent sexually transmitted infection during the period of SVR, syphilis being the modal infection.

Conclusions: Of 8 individuals, 6 who had further HC viremia following SVR, were re-infected with a different HCV strain. Re-infections were likely related to ongoing high-risk sexual activity. The clustering seen indicates that this is a relatively closed population, exchanging HCV within the cohort. In 2 cases, the strains were closely related indicating either late relapse or possibly re-infection from a common source.