Eighteen per cent of HIV-positive men
acquired hepatitis C virus (HCV) a second time after clearing the virus, with
some having third and fourth infections as well, according to findings from the
European AIDS Treatment Network (NEAT) presented at the 14th European
AIDS Conference this month in Brussels.
Since around 2000,
researchers have been reporting outbreaks of apparently sexually transmitted
acute hepatitis C among HIV-positive men who have sex with men in major cities,
first in the UK and continental Europe, then followed by Australia and the US.
Factors associated with HCV transmission, which differ across studies, include
anal intercourse, fisting, group sex, presence of other sexually transmitted infections and
use of non-injected recreational drugs.
Up to one quarter
of people with acute HCV infection clear the virus without treatment, whilst the
remainder develop chronic hepatitis C lasting more than six months; spontaneous
clearance is less common (around 15 to 20%) amongst people with HIV. Treatment
with interferon-based therapy is highly effective during acute infection. However,
people who clear HCV naturally or with treatment remain susceptible to
An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
from the Medical Centre for Infectious Diseases and fellow investigators with
the NEAT Study Group looked at rates of HCV reinfection amongst HIV-positive
people in the UK, Austria and Germany.
included 646 men with HIV seen at six NEAT centres since 2002 who had had acute
hepatitis C with either spontaneous clearance (12%) or treatment-induced cure
(88%). Men with a second or subsequent HCV infection were included in the
Reinfection was defined as
detectable HCV RNA after confirmed spontaneous
clearance (negative HCV RNA at 24 weeks after diagnosis) or more than 24
weeks after sustained virological response (SVR) to treatment, or infection
with a different genotype or clade than the initial infection.
Overall, 113 men (18%) were identified
as having at least a second episode of HCV infection, which occurred a median of
162 weeks after the first. Almost all were gay or bisexual men with a median
age of 38 years and nearly half had the favourable IL28B 'CC' gene variant. They
had well-controlled HIV disease, with 67% being on antiretroviral therapy (ART),
half having undetectable viral load, and a median CD4 cell count of 538
cells/mm3. The most common HCV genotype was 1 (71%), followed by 4
(17%) and 3 (11%); 45% showed a switch of HCV genotypes between their first and
had a third episode of HCV infection, occurring a median of 122 weeks after the
second diagnosis. Here, 81% were genotype 1 infections, 13% were genotype 4 and
6% were genotype 3; half had a switch from their previous genotype.
three people who went on to become infected a fourth time, occurring a median
of 52 weeks after the third diagnosis. Two had genotype 1 and one had genotype
4, with two out of three showing a switch in genotypes.
While 12% of
participants had spontaneously cleared HCV and 88% had achieved SVR with
treatment following the first infection, 17% experienced spontaneous clearance
of the second infection, 47% cleared the third infection and 33% cleared the
people who did not spontaneously clear HCV underwent treatment with pegylated
interferon plus ribavirin; two also received telaprevir (Incivo or Incivek) and
one also received simeprevir (an experimental HCV protease inhibitor).
rate for treatment of the second infection was 45%; 19% were non-responders
(about 15% were still being treated or in post-treatment follow-up). Cure rates
appeared lower during the third and fourth episodes, but numbers were small and
some of participants were still awaiting SVR data.
and use of ART did not predict spontaneous clearance of the second infection.
Clearers were more likely to have the favourable IL28B gene variant (71 vs
44%) and had lower HCV RNA and higher alanine aminotransferase (ALT), but none
of these differences reached statistical significance. The only significant
predictor was clearance of the first infection, which occurred in 32% of second
infection clearers and 9% of non-clearers.
the third episode, spontaneous clearers and non-clearers were equally likely to
have the IL28B 'CC' variant (50% each) and HCV RNA was higher amongst clearers,
though not significantly so. Previous clearers were again
more likely to clear their subsequent infection (33% of third infection
clearers vs 10% of non-clearers), but this time the difference did not reach
"We confirm high HCV
reinfection rates in HIV-positive men who have sex with men with one cured
episode of HCV," the researchers concluded. "Spontaneous clearance
rates seem to increase with reinfection episodes...Spontaneous clearance of a
previous episode increases the likelihood to clear again."
"We observed reinfections with
the same or with a distinct HCV genotype, and did not find any evidence of
immune protection when reinfected with the same genotype," they added.
"Understanding of risk behaviours
and promoting strategies for risk-avoidance will be important to prevent
reinfections in this population," they recommended.