Reappearance of HCV in Gay Men Is Usually Due to Re-infection, Not Late Relapse

Re-emergence of hepatitis C virus (HCV) in gay and bisexual men who were previously treated and achieved sustained virological response with interferon-based therapy appears to be due to reinfection, not late relapse occurring after the usual window for determining a cure, according to a genetic sequencing study described in the April 1, 2010 Journal of Acquired Immune Deficiency Syndromes.

Outbreaks of apparently sexually transmitted acute hepatitis C virus (HCV) infection, mostly among HIV positive men who have sex with men, have been reported over the past decade in cities in the U.K., Europe, Australia, and the U.S. Many of these men have been treated successfully, but in a few cases HCV was later detected again.

Rachel Jones from Chelsea and Westminster NHS Foundation and colleagues performed genetic sequencing in an effort to determine whether HCV reappearance could be attributed to new infection or to late relapse after apparent sustained virological response (SVR). Unlike hepatitis A and B, clearing HCV once does not confer immunity against later reinfection.

Typically hepatitis C is considered "cured" if a person continues to have undetectable HCV viral load 24 weeks after completing a course of treatment. After this point, relapse is very rare among HIV negative people, but this has not been well studied in HIV/HCV coinfected individuals.

The investigators retrospectively analyzed data from Chelsea and Westminster and the Royal Free Hospital in London to identify HIV positive patients who were diagnosed with acute hepatitis C between 1999 and 2008. Out of more than 200 such individuals, they identified 22 who presented with HCV again after they had cleared the virus.

All these patients were gay or bisexual men with no history of injection drug use. The average age was 40 years, most were on antiretroviral therapy (ART), and they had generally well-controlled HIV disease with a median baseline CD4 count of about 450 cells/mm3. Two men experienced spontaneous HCV clearance the first time, and the rest were apparently cured with 24 weeks of pegylated interferon plus ribavirin (the standard duration for acute hepatitis C).

The researchers analyzed E1/E2 gene sequences from paired samples collected from 9 of these participants during the first and second episodes of HCV viremia and constructed phylogenetic trees to determine how closely the virus isolates in the 2 samples were related.

Results

• The second episode of detectable HCV viral load occurred 22 months on average after the first episode.
• 18 men had 27 diagnoses of other sexually transmitted infections (mainly syphilis and gonorrhea) between the 2 HCV episodes, indicating continued unprotected sex.
• 1 patient was initially infected with HCV genotype 4 (uncommon in Europe except among clusters of coinfected gay men), followed by genotype 1a the second time.
• 6 other men had the same genotype in the first and second infection, but specific viral isolates were only distantly related, indicating re-infection rather than relapse of the original virus.
• Remaining samples showed HCV isolates that were closely enough related that they could have been either cases of re-infection or late relapse.
• Many of the HCV isolates detected during second episodes of infection were related to each other, however, suggesting transmission within a sexual network.

Based on these findings, the researchers concluded that reappearance of HCV was typically due to re-infection rather than relapse, and that recurrent episodes were "strongly related to levels of ongoing risk behavior."

They recommended that providers screen HIV positive patients for HCV and determine genotypes for those found to be infected -- even if not planning to undergo hepatitis C treatment. They also stressed the need for better education about HCV sexual transmission and intensified prevention efforts for men who have sex with men.

Investigator affiliations: Chelsea and Westminster NHS Foundation Trust, London, UK; Royal Free and University College Medical School, London, UK; University of New South Wales, Sydney, Australia; Oxford University, Oxford, UK.

7/6/10

Reference
R Jones, D Brown, M Nelson, and others. Re-emergent hepatitis C viremia after apparent clearance in HIV-positive men who have sex with men: reinfection or late recurrence? Journal of Acquired Immune Deficiency Syndromes 53(4): 547-550. April 1, 2010.