Re-emergence of HCV in British Gay Men Appears to Be Reinfection, Not Late Relapse

By Liz Highleyman

Several outbreaks of apparently sexually transmitted acute hepatitis C virus (HCV) infection have recently been reported in cities in the U.K., continental Europe, and Australia, mostly among HIV positive gay/bisexual men. In a number of cases, these men were treated successfully but then experienced a re-emergence of HCV.

In a late-breaker presentation at the 15th Conference on Retroviruses and Opportunistic Infections last week in Boston, researchers described the results of an analysis to determine whether these men experienced late relapse after treatment or were reinfected with HCV. Clearance of HCV, spontaneously or with treatment, does not produce an immune response that protects against subsequent infection.

The investigators looked at data from Chelsea and Westminster and the Royal Free Hospital in London. Of the 211 HIV-HCV coinfected patients in the database, they identified 16 who had 2 or more episodes of HCV viremia. All were HIV positive men who have sex with men (MSM) with no history of injection drug use; overall, they had well-controlled HIV disease, with a CD4 cell count of nearly cells/mm3, and most (11) were on HAART.

All of the men had been treated with pegylated interferon plus ribavirin during their first episode of acute HCV infection and had achieved sustained virological response (SVR) 6 months after completing therapy; SVR is widely regarded as a "cure," and relapse after this point is uncommon. Re-emergent HCV infection was detected following an increase in alanine aminotransferase (ALT) during regular HIV care.

The researchers analyzed E1/E2 sequences from paired HCV samples from the first and second episodes of HCV viremia from 8 of the men (all genotype 1) and constructed phylogenetic trees to determine how closely the 2 samples were related.

Results

• The average duration of treatment response before detection of the second episode of HCV viremia was 28 months (range 6-55).

• In 2 of the 8 men with genetic analyses, the HCV samples were closely related.

• The other 6 had divergent samples, suggesting reinfection with a new strain of HCV.

• HCV genotypes in these 6 were the same as the initial infection.

• Most of the analyzed HCV strains were clustered, suggesting reinfection within a "closed population" of HIV positive MSM.

• 14 of the 16 men with re-emergent HCV had 1 or more concurrent sexually transmitted infections (10 with syphilis, 6 with gonorrhea, 3 with new or recurrent herpes).

• Further follow-up showed that 2 of the men experienced a third re-emergence of HCV after a second course of interferon-based treatment.

Conclusion

"Of 8 individuals, 6 who had further HCV viremia following SVR were re-infected with a different HCV strain," the researchers concluded. "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."

They added that in the 2 remaining cases, "the [HCV] strains were closely related indicating either late relapse or possibly re-infection from a common source."

Based on these findings, the presenter, Rachael Jones of Chelsea and Westminster, recommended implementation of a stronger public health information and screening program for hepatitis C, especially for HIV positive men who have sex with men.

Chelsea and Westminster NHS Fndn Trust, London, UK; Royal Free and Univ Coll Med Sch, London, UK; Oxford Univ, UK; Univ of New South Wales, Sydney, Australia.

2/12/08

Reference
R Jones, D Brown, M Nelson, and others. Hepatitis C Viremia following Sustained Virological Response to Pegylated Interferon and Ribavarin in HIV+ Men Who Have Sex with Men-Re-infection or Late Relapse? 15th Conference on Retroviruses and Opportunistic Infections. Boston, MA. February 3-6, 2008. Abstract 61LB.

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