There is a very
high incidence of hepatitis C virus (HCV) reinfection among HIV-positive men
who have sex with men (MSM) in western Europe, according to research presented
to the International Liver Congress in Barcelona. Investigators found that a
quarter of HIV-positive MSM who cleared an initial HCV infection were reinfected
with HCV within three years. The researchers believe that current prevention
strategies are failing and call for the intensive monitoring of people who
have apparently cleared an HCV infection.
There are ongoing
HCV epidemics among HIV-positive MSM in many industrialised countries. There is
convincing evidence of sexual transmission, with unprotected anal sex, fisting
and re-use of injecting equipment identified as high-risk activities. A recent meta-analysis
suggested that prevalence of HCV co-infection among HIV-positive MSM is between
5 and 6%.
HCV infection can
be cured with therapy and spontaneous clearance of acute infection has also been documented.
Glossary
- IL28B
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.
Research conducted
in Amsterdam and London has found a high incidence of HCV reinfection after
successful treatment or spontaneous clearance. There are several reasons why it
is important to establish a clearer understanding of the incidence of
reinfection and its risk factors, including prevention and screening
strategies. Moreover, reinfection could affect the cost/benefit of expensive,
but highly effective new therapies.
Investigators from
the UK, Germany, Austria and France therefore designed a study to estimate the
incidence of HCV reinfection among HIV-positive MSM who cleared the virus either
after therapy or spontaneously.
The study
population consisted of 606 men with confirmed cure or spontaneous clearance.
Patients who received therapy were considered cured if they had a negative HCV
PCR twelve weeks after the completion of therapy; cure following spontaneous
clearance was a negative HCV PCR result 24 weeks after the first negative PCR.
Data were
collected on age, date of HCV diagnosis, HCV genotype, HCV and HIV viral load,
use of antiretroviral therapy (ART), CD4 count and liver function (maximum ALT). Data were also
requested on presence of the IL28B gene – associated with favourable outcomes –
but response rates were poor.
Reinfection was
defined as a positive HCV PCR after confirmed cure/spontaneous clearance.
Over three years
of follow-up, 149 patients (24.6%) were reinfected. The median time to
reinfection was 1.8 years. Median age at the time of reinfection was 41
years. Most individuals – 91 of 111 patients with available data – had an
undetectable HIV viral load at the time of reinfection and median CD4 cell
count was 533 cells/mm3.
Spontaneous
clearance of the initial infection was observed in 15%
of patients after reinfection. 113 people received antiviral treatment, of whom 87 were cured.
A second
reinfection was recorded in 29 patients, four patients were reinfected three
times and a single individual had four reinfections.
Just over a
quarter (29%) of patients spontaneously cleared their second reinfection and a
third experienced spontaneous clearance of their third reinfection.
Overall incidence
of reinfection was 7.6 per 100 person-years. Incidence of second reinfection
was even higher at 19.9 per 100 person years.The incidence of reinfection was markedly higher in Paris (21.8 per 100 p.y.) and Vienna (16.8 per 100 p.y.) than in London (7 per 100 p.y. ) and German centres (5-8 per 100 p.y.) but the amount of patient follow-up available for analysis makes it difficult to draw firm conclusions.
Spontaneous
clearance of the initial infection was associated with a significant reduction
in the risk of reinfection (HR = 0.55; 95% CI, 0.32-0.95) and also the chances
of spontaneous clearance if reinfected (OR = 12.7; 95% CI, 2.3-70.2).
The investigators
conclude that there is a substantial risk of HCV reinfection for HIV-positive
MSM. They believe their results show the failure of current prevention
interventions and underline the need for new strategies. The researchers also
suggest their findings have implications for the monitoring of co-infected MSM
and call for HCV PCR testing to be performed every three to six months after HCV
infection and every three months after reinfection.