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.
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
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
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
second episode of detectable HCV viral load occurred 22
months on average after the first episode.
men had 27 diagnoses of other sexually transmitted infections
(mainly syphilis and gonorrhea) between the 2 HCV episodes,
indicating continued unprotected sex.
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.
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.
samples showed HCV isolates that were closely enough related
that they could have been either cases of re-infection or
of the HCV isolates detected during second episodes of infection
were related to each other, however, suggesting transmission
within a sexual network.
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.
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