In a related study reported in the September 17 online edition of Journal
of Hepatology, Patrick Ingiliz and fellow investigators with
the NEAT study group did an analysis of HCV reinfection rates among
HIV-positive gay and bi men in Europe.
Up to a quarter of people with acute HCV infection – somewhat
less if HIV-positive – will naturally clear the infection without treatment,
while the remainder develop chronic or long-term infection. HCV usually does
not confer full protective immunity and people can be reinfected after
spontaneous clearance or successful treatment. However, it appears that
spontaneous clearance becomes more likely with subsequent infections,
suggesting the immune system may get better at controlling HCV.
HCV reinfection remains a
possibility for individuals with ongoing risk behaviour, including people who inject drugs and men who have sex with men. One meta-analysis of 61 studies found that the five-year risk of HCV
reinfection among HIV-positive MSM was as high as 15% – higher than in most
studies of people who inject drugs, the study authors noted as background.
This retrospective analysis included 606 HIV-positive
MSM at eight centres in the UK, Austria, France and Germany within the European
AIDS Treatment Network who were followed between May 2002 and June 2014.
Of these, 111 men spontaneously cleared their initial
HCV infection (two negative HCV tests at least 24 weeks apart after a positive
test), while 494 were cured with pegylated interferon plus ribavirin (SVR12, or
undetectable HCV RNA at 12 week post-treatment).
During follow-up 149 participants (24.6%) presented with subsequent HCV reinfection after
viral clearance, defined as recurrent detectable HCV RNA after these
time points, or within these time frames if the HCV genotype was different. The
median CD4 count at the time of reinfection was 533 cells/mm3 and
82% had undetectable HIV viral load. Almost all had elevated alanine
aminotransferase (ALT), a marker of liver inflammation.
Of the 70 men who
spontaneously cleared HCV a second time or were successfully treated again, 30
(43%) presented with a second reinfection. In addition, five men had a third
reinfection and one had a fourth reinfection.
The overall incidence of first HCV reinfection among
552 patients with complete data was 7.3 per 100 person-years (PY), occurring a
median of two years after clearance. Reinfection rates varied considerably
across centres, ranging from 5.0 per 100 PY in Hamburg to 21.8 per 100 PY in
Paris. The incidence of a second reinfection was much higher, at 18.8 per 100
The researchers noted a trend toward a lower
reinfection rate among people who spontaneously cleared HCV compared to those
who were cured with treatment, but the difference did not reach statistical
significance (4.9 vs 7.8 per 100 PY; p = 0.06).
Looking at outcomes among men who were reinfected,
15.6% spontaneously cleared their first reinfection and 28.6% did so after
their second reinfection – possibly indicating increased HCV-specific immune
responses. Spontaneous clearance of reinfection was associated with ALT levels
>1000 IU/ml and spontaneous clearance of the first HCV infection.
“We found a high reinfection incidence of
7.3/100 PY with an estimate that almost one-third of patients [were] reinfected
after five years,” the study authors summarized.
“These numbers highlight the failure of current
prevention strategies and the need for specific measures in the HIV-infected MSM
population at risk in Europe,” they wrote in their discussion. “As new, well
tolerated, but costly HCV treatments have become the standard of care for HCV
therapy, there is an urgent need to develop strategies to prevent reinfection
at such scale.”
The higher incidence of second reinfection compared
to first reinfection “indicates a maintained risk behaviour in a potentially
specific high-risk group, who require urgent targeting for prevention measures
related to risk behaviours,” the authors added. They recommended that
HIV-positive gay men who have been infected once with HCV should be tested for
reinfection every three to six months, and those who have been reinfected
should be retested every three months.