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Hepatitis C Virus Infections in the Swiss HIV Cohort Study: A Rapidly Evolving Epidemic

8/31/2012

1 Comment

 
This study assessed trends in HCV
  incidence in the different HIV transmission groups in the Swiss HIV Cohort
Study  (SHCS) in order to optimize surveillance and prevention......In
MSM,  history of inconsistent condom use (aHR: 2.09, 1.33-3.29) and past
syphilis  (2.11, 1.39-3.20) predicted HCV seroconversions.....IDUs are the
prevalent group  with HCV in HIV+ in the Swiss Cohort but the high increasing
incident rate among  HIV+ MSM (increased 18-fold in the last 13 years) reflects
a trend observed and  reported in Western Europe in major cities & reported
at conferences over  the past few years....."In
MSM,  history of inconsistent condom use (aHR: 2.09, 1.33-3.29) and past
syphilis  (2.11, 1.39-3.20) predicted HCV seroconversions.....In the SHCS, the large  majority of recent HCV
infections occurred in MSM"......"suggests that 3-monthly  screening with liver
function tests is costeffective in settings with  HCV-incidences above 1.25%.
Accordingly, our results should provide important  information for establishing
cost-effective screening programs in  HIV-infected patients. However, routine
serological screening does not prevent  risk behaviour, and coordinated efforts
between physicians and public-health  representatives are needed to control the
ongoing HCV infection epidemic in  HIV-infected MSM.....It
is crucial that HIV-infected MSM are counselled  with regard to the risks of
sexual activities that involve traumatic mucosal  sex, and that condoms are used
consistently in sexual risk situations  [28]. The example of IDUs demonstrates
that it is possible to reduce the  incidence of HCV-infections through improved
screening and preventive  interventions......Accordingly,  the intervals of HCV-screening will be
reduced to 1 year in the SHCS. This  should allow identifying patients with new
HCV-infections earlier in order to  optimize counselling with regard to HCV
transmission risks, and to improve  the response to HCV-therapy by initiating
treatment during acute infection. The  revised screening practice in the SHCS is
in line with recent guidelines which  recommend yearly screening for all
HIV-infected MSM who still engage in any risk  behavior [33-35]. Furthermore, a
recent study demonstrated that yearly  serological HCV screening and 6-monthly
liver function testing is cost-effective  [36]. Importantly, this analysis
demonstrated that the optimal screening  strategy strongly depends on
HCV-incidence"


"It is
  crucial that HIV-infected MSM are counselled with regard to the risks of sexual
  activities that involve traumatic mucosal sex, and that condoms are used
  consistently in sexual risk situations [28]. The example of IDUs demonstrates
  that it is possible to reduce the incidence of HCV-infections through improved
  screening and preventive interventions.....
This underscores the need for improved HCV
  surveillance and prevention among HIV-infected MSM. Accordingly, the intervals
  of HCV-screening will be reduced to 1 year in the SHCS. This should allow
  identifying patients with new HCV-infections earlier in order to optimize
  counselling with regard to HCV transmission risks, and to improve the response
  to HCV-therapy by initiating treatment during acute infection"

"Of 4,629 MSM, 2,678
IDU  and 4,530 HET screened for HCV infection, 3,333 (72%), 123 (5%) and 3,078
(68%)  had a negative HCV serology
at baseline and available serological
follow-up.  Over 23,707 person-years (py) for MSM, 733 py for IDU and 20,752 py
for HET, 101  (3%), 41 (33%) and 25 (1%) seroconverted, respectively. The IR
of HCV  infections in MSM increased from 0.23 (95% CI: 0.08-0.54) per 100py in
1998 to  4.09 (2.57-6.18) in 2011.
The IR decreased in IDU and remained
below 1 per  100 py in HET. In MSM, history of inconsistent condom use (aHR:
2.09, 1.33-3.29)  and past syphilis (2.11, 1.39-3.20) predicted HCV
seroconversions.


Conclusions. In the SHCS, HCV incidence
  decreased in IDU, remained stable in HET and increased 18-fold in MSM in the
  last 13 years. These observations underscore the need for improved HCV
  surveillance and prevention among HIV-infected MSM."



Most
demographic and  behavioural characteristics were similar in HCV-seroconverters
compared to  patients who did not seroconvert (Web-Table 1). Median age was 34.9
years in  seroconverters and 37.7 years in non-seroconverters, and the
proportion of  Caucasians was 93% and 92%, respectively. In both groups, over
90% of patients  started ART before or during follow-up. However, previous HBV
exposure, a past  history of syphilis and inconsistent condom use were more
common in  HCV-seroconverters (Web-Table 1). The incidence of HCV infections was
higher in  patients who reported inconsistent condom use, as well as in those
who had a  previous episode of syphilis or exposure to HBV compared to the other
patients  (Figure 3). In adjusted Cox regression analyses, only inconsistent
condom use  (adjusted Hazard Ratio (aHR): 2.09,
95% CI  1.33-3.29) and previous diagnosis of syphilis (2.11,
1.39-3.20) were significantly associated  with HCV seroconversions (Table
2).


In the SHCS, the large majority
of  recent HCV infections occurred in MSM. This underscores the need for
improved  HCV surveillance and prevention among HIV-infected MSM. Accordingly,
the  intervals of HCV-screening will be reduced to 1 year in the SHCS. This
should  allow identifying patients with new HCV-infections earlier in order to
optimize  counselling with regard to HCV transmission risks, and to improve the
response  to HCV-therapy by initiating treatment during acute infection. The
  revised screening practice in the SHCS is in line with recent guidelines which
  recommend yearly screening for all HIV-infected MSM who still engage in any
risk  behavior [33-35]. Furthermore, a recent study demonstrated that yearly
  serological HCV screening and 6-monthly liver function testing is
cost-effective  [36]. Importantly, this analysis demonstrated that the optimal
screening  strategy strongly depends on HCV-incidence.


For instance, it suggests that 3-monthly
screening with liver  function tests is costeffective in settings with
HCV-incidences above 1.25%.  Accordingly, our results should provide important
information for establishing  cost-effective screening programs in HIV-infected
patients. However, routine  serological screening does not prevent risk
behaviour, and coordinated efforts  between physicians and public-health
representatives are needed to control the  ongoing HCV infection epidemic in
HIV-infected MSM. Although most reported  HCV-transmissions among MSM occurred
in HIV-infected patients, it is conceivable  that HCV-incidence among
HIV-negative MSM is underestimated as these individuals  are not in regular
medical care. Clinicians and patients should be aware of  the risk of acute  HCV
infection in MSM, and intensified prevention and counselling should be
  performed. Despite the fact that antiretroviral treatment is highly efficient
  in preventing HIV-transmission it does not have any effect on prevention of
  other sexually transmitted diseases. Condom use declined in recent years in MSM
  with suppressed HIV viral load in the SHCS [37], which likely contributes to
the  increasing incidence of HCV-infections in this population. It is crucial
that  HIV-infected MSM are counselled with regard to the risks of sexual
activities  that involve traumatic mucosal sex, and that condoms are used consistently  in sexual risk
situations [28]. The example of IDUs demonstrates that it is  possible to reduce
the incidence of HCV-infections through improved screening  and preventive
interventions.


 
Abstract
Background.  Hepatitis C Virus (HCV)
  infection has a growing impact on morbidity and mortality in HIV-infected
  patients. We assessed trends in HCV incidence in the different HIV transmission
  groups in the Swiss HIV Cohort Study (SHCS) in order to optimize surveillance
  and prevention.


Methods. HCV infection incidence was
  assessed from 1998, when routine serial HCV screening was introduced in the
  SHCS, until 2011. All HCV-seronegative patients with at least one follow-up
  serology were included. Incidence rates (IR) of HCV infections were compared
  between men who have sex with men (MSM), injection drug users (IDU) and
  heterosexuals (HET). Predictors of HCV seroconversion in MSM were estimated.



Results. Of 4,629 MSM, 2,678 IDU and
  4,530 HET screened for HCV infection, 3,333 (72%), 123 (5%) and 3,078 (68%) had
  a negative HCV serology at baseline and available serological follow-up. Over
  23,707 person-years (py) for MSM, 733 py for IDU and 20,752 py for HET, 101
  (3%), 41 (33%) and 25 (1%) seroconverted, respectively. The IR of HCV
infections  in MSM increased from 0.23 (95% CI: 0.08-0.54) per 100py in 1998 to
4.09  (2.57-6.18) in 2011. The IR decreased in IDU and remained below 1 per 100
py in  HET. In MSM, history of inconsistent condom use (aHR: 2.09, 1.33-3.29)
and past  syphilis (2.11, 1.39-3.20) predicted HCV seroconversions.


Conclusions. In the SHCS, HCV incidence
  decreased in IDU, remained stable in HET and increased 18-fold in MSM in the
  last 13 years. These observations underscore the need for improved HCV
  surveillance and prevention among HIV-infected MSM.                  




Hepatitis C Virus (HCV) infection is a
major cause of morbidity and  mortality in HIV-infected patients [1-3]. For many
years, HCV-infections  occurred almost exclusively in injection drug users (IDU)
or hemophiliacs. In  a previous analysis in the Swiss HIV Cohort study
(SHCS), HCV seroprevalence was  33% overall and 90% among individuals reporting
IDU
[4]. Recently, there  have been several outbreaks of HCV infections
among HIV-infected men who have  sex with men (MSM), predominantly in large
cities in Europe, Australia and the  USA [5-14]. These clusters of HCV
infections involved high-risk sexual practices  within confined social networks.
However, the impact of these localized  epidemics on the incidence of HCV
infections in general HIV-infected populations  and the long-term trends in HCV
incidence rates in different transmission risk  groups are largely unknown. A
better understanding of changes in  HCV-incidence rates and transmission
patterns is urgent because of the  increasing burden of HCV-related disease in
HIV-infected patients  [1-3].



The SHCS offers an ideal platform for
studying changes in HCV  incidence in a general HIV-infected population and in
diverse HIV-transmission  risk groups, as all HCV seronegative patients are
screened routinely at baseline  and during follow-up since 13 years.
Furthermore, it allows a thorough  evaluation of the association of HCV
seroconversions with different risk  factors, as detailed patient history and
clinical data is collected every six  months.


We assessed changes in the HCV infection
incidence in the three main  HIV transmission groups (IDU, MSM and heterosexuals
(HET)) in the SHCS during  the last 13 years, with the expectation that our
results would shed light on the  magnitude and changes of the HCV epidemic in a
general and representative  HIV-infected population.



METHODS
Swiss HIV cohort Study
The Swiss HIV Cohort Study (SHCS, www.shcs.ch) is a prospective cohort study  with
ongoing enrolment of HIV-infected adults in Switzerland since 1988. It  covers
at least 45% of the cumulative number of HIV infections declared to the  Swiss
public health authorities, 69% of all patients living with AIDS and 75% of
  patients receiving antiretroviral therapy in Switzerland [15]. Representativity
  remained stable over the years. Detailed information on demographics, mode of
  HIV acquisition, risk behavior, clinical events, co-infections, and treatment
is  collected using a standard protocol at registration and then at intervals of 6 months. Local
  ethical committees of all participating study sites have approved the study and
  written consent has been obtained from all participants.



Inclusion criteria and
definitions

To compare HCV incidence between risk
groups, we categorised patients  as IDU, MSM or HET according to the most
probable HIV-transmission mode. In  order to minimize erroneous classifications,
we excluded MSM and HET patients  who reported the use of injection drugs at any
occasion during follow-up. Since  1998, all SHCS patients have been routinely
screened for HCV infection: serology  is performed every second year of
follow-up, independently of HIV transmission  mode. Thus, all HCV-seronegative
patients who had at least one follow-up HCV  antibody measurement after July
1998 were included in the analyses. Positive  results by third-generation ELISA
are confirmed by immunoblot. Patients with a  positive HCV serology at entry,
and those who seroconverted before 1998 were  excluded. Individual follow-up
ended at the time of the first positive or last  negative HCV serology. A
detailed patient flow chart is shown in Figure 1.  Previous syphilis was defined
as a positive  Treponema-pallidumhemagglutination-assay (TPHA) screening test
and hepatitis B  virus (HBV) exposure by the presence of a positive anti-HBc
antibody test prior  to HCV seroconversion, or before
the last negative HCV-serology in those
without HCV seroconversion.  In this context, the term HBV exposure refers to
both resolved and chronic HBV  infections. A subset of HCV seroconverters was
found to have a unique positive  HCV serology followed by one or several
negative serologies. These patients  could have cleared HCV antibodies after
spontaneous HCV clearance, as described  before [16-18]. Alternatively, false
positive results cannot be excluded despite  confirmation by HCV-immunoblot.
Therefore, the main analyses were repeated after  exclusion of these
cases.


Statistical analyses
HCV incidence rates were assessed from
introduction of routine  HCV-screening from July 1998 until November 2011.
Patients were considered to be  at risk for HCV infection since the date of
their first negative HCV serology or  since 01.07.1998 if the first measurement
preceded this date. Individual  follow-up ended at the time of the first
positive or last negative HCV serology.  Baseline characteristics were compared
between the three risk groups using  analysis of variance (ANOVA) and
chi-squared tests for continuous and  categorical variables, respectively. To
calculate the incidence of  HCV infections in the different risk groups, events
were right-censored so that  the date of seroconversion corresponded to the date
of the first positive HCV  serology. Yearly HCV infection incidence rates (IR)
were obtained using Bayesian  Poisson regression models with non-parametric
smoothing priors [19]. IR are  reported as number of cases per 100 person-years
(py) and shown on a log scaled  graph, by transmission group (MSM, IDU,
HET).



In sensitivity analyses, the yearly rates
of HCV infection in MSM  were compared to the results obtained using two
alternate censoring approaches:  (1) Mid-point censoring, in which the date of
seroconversion was set to the  mid-point between the last negative and first
positive HCV serology, and (2) a  non-parametric maximum likelihood estimation
method for interval-censored data  [20]. Interval-censoring takes into account
that the exact date of  seroconversion is not known but lies between the last
negative and the  first positive serology. However, due to the low number of
seroconversions in  IDU and HET, this method could only be applied to the MSM
risk  group.


Demographic characteristics of
HCV-seroconverters in MSM were  compared to those who did not seroconvert during
follow-up using Chi-square and  Mann-Whitney tests. The difference in incidence
of HCV infections between  patients of different age groups, condom use
patterns, hepatitis B exposure  status and history of past syphilis were also
shown in log-scaled graphs. Risk  factors for HCV infection in MSM were
evaluated using a multivariable Cox  regression model. Analyses were adjusted
for age category (16-29, 30-39 and > =40 years), CD4 count category before
last HCV serology (<200, 200-499  and >=500 cells/ μl), education level
(no, basic and high-level  professional education), region of SHCS follow-up
(Zurich or other), ethnicity  (Caucasian or other), use of non-IDU drugs (yes or
no), sexual relationships  (stable or occasional partners), condom use (always
or inconsistent), past  history of syphilis (yes or no), HBV exposure (yes or
no) and antiretroviral  therapy (ART) status (yes or no). All statistical
analyses were performed using  Stata 12 (Stata Corp, College Station, USA) and
R-2.14.1 [21] using add-on  packages INLA [22] and Icens [23].





RESULTS


Baseline
characteristics

Of 4,629 MSM, 2,678 IDU and 4,530 HET
screened for HCV infection, 147  (3.2%), 2,468 (92.2%) and 513 (11.3%) had a
positive HCV serology at baseline  (Figure 1). 6,534 patients, of which 3,333
MSM, 123 IDU and 3,078 HET, were  included in the HCV incidence analyses. Median
age at first HCV screening test  was slightly higher in MSM (38 years,
inter-quartile range (IQR) 32-44) and HET  (36, 30-44), compared to IDU (33,
28-40), whereas MSM were more likely to have a  high-level education than
patients in the two other groups (Table 1). Almost  half of the MSM and IDU, but
only 29% of HET had their regular medical follow-up  in Zurich, Switzerland’s
largest urban center. Finally, HET were much more  likely to be non-Caucasians
(40.7%), compared to MSM (7.7) and IDU (8.9). HCV  incidence


Over a total follow-up time of 23,707
person-years (py) for the  MSM group, 733 py for the IDU group and 20,752 py for
the HET group, 101 (3.0%),  41 (33.3%) and 25 (0.8%) patients experienced an HCV
seroconversion during  follow-up, respectively. Between 1998 and 2011, the IR of
HCV infections in MSM  increased from 0.23 (95% CI: 0.08-0.54) per 100 py to
4.09 (2.57-6.18) in  2011in2011, with 51 cases observed in the last 3 years
(Figure 2). There was a  similar increase in patients followed in Zurich
compared to the rest of the  country (IR in 2011 were 2.61 (1.19-5.13) and 4.10
(2.18-7.16) per 100  py, respectively). Increases in HCV-incidence in MSM were
similar when  right-censoring, midpoint-censoring or interval-censoring were
used to estimate  yearly incidence rates (Web-Figure 1).




In IDU, HCV infection IR decreased from
13.89 (95% CI: 8.20-22.39)  per 100 py in 1998 to 2.24 (0.55-10.66) in 2011,
with only 3 incident cases in  the last 3 years.
For comparison, the yearly
IR of HCV infections in the HET  group remained below 0.5 per 100 py, with only
2 cases in 2011 (IR 0.43 per  100py, 95% CI: 0.12-1.29; Figure 2). Twenty-five
(15.0%) HCV-seroconverters had  a unique positive serology followed by negative
tests. Of those, six patients  had their HCV infection confirmed by HCV RNA
testing within one month of the  positive serology. In another eight patients,
HCV RNA testing was negative,,  which may be reflective of spontaneous HCV
clearance and loss of HCV-antibodies  over time. Eleven patients did not have an
HCV RNA available to confirm the HCV  infection. After exclusion of these
patients, the incidence rates of  HCV infection remained similar to the results
described above (1998: MSM: 0.11  per 100 py, 95% CI 0.03-0.35; IDU: 14.36,
8.36-23.39; HET: 0.09, 0.02-0.35.  2011: MSM: 3.56, 2.19-5.53; IDU: 2.42,
0.51-13.36; HET: 0.47,  0.14-1.30).



Predictors of HCV infections in
MSM

Most demographic and behavioural
characteristics were similar in  HCV-seroconverters compared to patients who did
not seroconvert (Web-Table 1).  Median age was 34.9 years in seroconverters and
37.7 years in  non-seroconverters, and the proportion of Caucasians was 93% and
92%,  respectively. In both groups, over 90% of patients started ART before or
during  follow-up. However, previous HBV exposure, a past history of syphilis
  and inconsistent condom use were more common in HCV-seroconverters (Web-Table
  1). The incidence of HCV infections was higher in patients who reported
  inconsistent condom use, as well as in those who had a previous episode of
  syphilis or exposure to HBV compared to the other patients (Figure 3). In
  adjusted Cox regression analyses, only inconsistent condom use (adjusted Hazard
  Ratio (aHR): 2.09,
95% CI 1.33-3.29)  and previous diagnosis of syphilis (2.11,
  1.39-3.20) were significantly associated with HCV seroconversions (Table
  2). Age, education level, CD4+
T cell  counts, ART status and the other variables included in the
multivariable model  were not significantly associated with the main outcome. Of
note, having  occasional sexual partners (aHR 0.97,
0.56-1.68) and being followed-up in Zurich (aHR 1.30,
  0.87-1.97) did not predict HCV seroconversions.


Of the 63 (62%) HCV infections in MSM with
detectable HCV RNA and  available genotyping results, the majority were caused
by HCV genotype 1 (42  cases, 66.7%), followed by genotypes 4 (12, 19.0%), 3 (8,
12.7%) and 2 (1,  1.6%).



DISCUSSION
We assessed trends in HCV incidence
between 1998 and 2011 in the main  HIV transmission groups in the SHCS. In a
population of over 6,500 patients  screened every 2 years for HCV infection, we
found that the yearly incidence  rate had decreased in IDU, remained stable in
HET and dramatically increased in  MSM. In the latter sub-population, 50% of all
HCV infections occurred in the  last three years. In MSM, a history of
inconsistent condom use and a past  episode of syphilis were significantly
associated with HCV  seroconversion.


Since 2005, several local reports
described epidemics of HCV  infections among HIV-infected MSM [7-12].
Phylogenetic and socio-demographic  analyses have shown that these infections
occurred within confined groups of MSM  with high-risk sexual behavior in large
urban centers [11, 24]. Therefore,  incidence estimates in these cohorts were
not representative for the general  HIV-infected population, in contrast to our
study. The systematic, nationwide  screening of all HIV-infected patients at
risk since 1998 allowed us to  accurately estimate the trends in HCV-incidence
among different risk groups.  Since 1998, the incidence of HCV infection among
MSM increased 18-fold, reaching  4.1 cases per 100 py in 2011. This incidence
was higher compared to the large  majority of previous studies among
HIV-infected MSM reporting estimates lower  than one case per 100 py [5].
However, the most recent HCV-incidence in the SHCS  was similar to estimates
from an international cohort collaboration of  HIV-seroconverters, where
incidence estimates ranged from 2.3 to 5.1/100 py in  2007 [25]. In accordance
to previous clusters of HCV-infections in large cities,  the HCV-incidence
increased markedly among individuals treated in Zurich, the  largest urban
center in Switzerland which, to some extent, is comparable to  other large
cities in Europe and the US. However, our study shows  that HCV-incidence
increased similarly outside of the Zurich area, indicating a  nationwide
increase in HCV-infections in HIV-infected MSM.



In line with previous reports [4, 8,
11], unprotected anal sex was  an important risk factor for HCV infections in
MSM. In the SHCS, inconsistent  condom use doubled the risk of HCV infection in
MSM. Furthermore, a previous  syphilis infection independently increased the
risk of an HCV seroconversion  approximately twofold. Of note, we recently
observed a significant increase in  syphilis acquisition among MSM in the SHCS,
paralleling the current HCV epidemic  [26]
. The shared route of transmission
of the two infections is the most  likely explanation for this association.
Alternatively, it is  also conceivable that the mucosal disruption caused by
syphilitic ulcers  facilitates HCV infections. These findings underscore the
importance of the link  between high risk sexual behavior and HCV transmissions.
As yearly syphilis  screening and baseline HBV serology testing are routine
for all MSM in the SHCS,  a positive test result should be an important warning
sign and lead to  intensified counseling on the prevention of sexually
transmitted HCV-infections  in these high-risk patients. Our results support
recent guidelines [27] to  screen HIV-infected MSM with high-risk sexual
behaviors or concomitant  ulcerative sexually transmitted diseases for hepatitis
C, and to screen  for syphilis in MSM with acute hepatitis C. Although the use
of non-injection  drugs has been associated with HCV infections among
HIV-infected MSM [28], we  found no association between non-injection drug use
and HCV seroconversions in  MSM
. However, we cannot exclude that our
analysis underestimates the  effect of non-injection drug use due to
underreporting of this behavior.
  Neither immunological status nor HIV-RNA
was associated with HCV-seroconversion:  the large majority (96%) of
HCV-infections occurred at CD4-T cell counts above  200/ul and most cases
(93%) were on ART.



The incidence of HCV infections in
HIV-infected IDU in the SHCS has  decreased in recent years, underscoring the
considerable success of preventive  interventions such as methadone substitution
and needle exchange programs in  reducing HCV-infections in IDUs followed in
routine HIV care. Furthermore,  Switzerland’s long-term heroin prescription
program likely contributed to the  decreasing incidence of HCV seroconversions
in this population. Besides a  reduction in risk behavior, it is also possible
that protective genetic markers  have been enriched during the course of the
epidemic in uninfected IDUs, as has  been demonstrated recently [29]. However,
the large majority (90%) of IDU were  excluded from the incidence analyses
because they already had a positive HCV  serology at entry, limiting the size of
the IDU population available for  the incidence calculations. In line with
previous studies [30, 31], the  incidence of HCV infection in HET has remained
very low, and we cannot exclude  that the few incident cases were related to
undisclosed IDU and/or MSM-related  sexual activity. This is corroborated by
recent phylogenetic studies within the  SHCS which revealed that
approximately 11% HIV-pol sequences from
heterosexuals were linked to  transmission clusters of MSM
[32].



The major strength of our study is the
long-term routine  HCV-screening at baseline and during follow-up in a
representative, nationwide  HIV-population and in different transmission groups.
Routine serological  surveillance of HCV infection is paramount to the diagnosis
of new infections,  as the majority of individuals experiencing such an event
remain asymptomatic,  and transaminase elevations can be transient and
unrecognized. Furthermore, we  could minimize transmission group
misclassification through the availability of  detailed longitudinal information
on sexual activity and drug abuse.  An important  limitation of our analysis resides in the
fact that we could not estimate  the exact HCV seroconversion dates between two
serological screening tests.  Furthermore, a limited number of patients might
have experienced  HCV-reinfections which cannot be recognized by serological
testing, possibly  leading to the underestimation of the true overall incidence
of HCV infections.  Similarly, the incidence might have been underestimated
through patients with  late or absent seroconversion, as described by Thomson et
al. [13]. A further  limitation lies in the sub-optimal sensitivity and
specificity of HCV antibody  assays. Although positive ELISA tests were
routinely confirmed by immunoblot,  false positive results cannot be entirely
excluded. Finally, some patients who  experienced an HCV seroconversion could
have lost their antibodies within a  few months after the infection in the
setting of spontaneous HCV-clearance  [16-18]. In the SHCS, 25 seroconverters
had a unique positive HCV serology,  followed by further negative tests.
However, incidence rates remained similar  after excluding these patients. In
the SHCS, the large majority of recent HCV  infections occurred in MSM.
This underscores the need
for improved HCV surveillance and  prevention among HIV-infected MSM.
Accordingly, the intervals of HCV-screening  will be reduced to 1 year in the
SHCS. This should allow identifying patients  with new HCV-infections earlier in
order to optimize counselling with regard to  HCV transmission risks, and to
improve the response to HCV-therapy by initiating  treatment during acute
infection
.
The revised screening practice in the SHCS is in line  with recent guidelines
which recommend yearly screening for all HIV-infected MSM  who still engage in
any risk behavior [33-35]. Furthermore,
a recent study  demonstrated that yearly serological HCV screening and 6-monthly
liver function  testing is cost-effective [36]. Importantly, this analysis
demonstrated that the  optimal screening strategy strongly depends on
HCV-incidence.


For instance, it suggests that 3-monthly
screening with liver  function tests is costeffective in settings with
HCV-incidences above 1.25%.  Accordingly, our results should provide important
information for establishing  cost-effective screening programs in HIV-infected
patients. However, routine  serological screening does not prevent risk
behaviour, and coordinated efforts  between physicians and public-health
representatives are needed to control the  ongoing HCV infection epidemic in
HIV-infected MSM. Although most reported  HCV-transmissions among MSM occurred
in HIV-infected patients, it is conceivable  that HCV-incidence among
HIV-negative MSM is underestimated as these individuals  are not in regular
medical care. Clinicians and patients should be aware of  the risk of acute  HCV
infection in MSM, and intensified prevention and counselling should be
  performed. Despite the fact that antiretroviral treatment is highly efficient
  in preventing HIV-transmission it does not have any effect on prevention of
  other sexually transmitted diseases. Condom use declined in recent years in MSM
  with suppressed HIV viral load in the SHCS [37], which likely contributes to
the  increasing incidence of HCV-infections in this population. It is crucial that HIV-infected MSM are
  counselled with regard to the risks of sexual activities that involve traumatic
  mucosal sex, and that condoms are used consistently in sexual risk situations
  [28]. The example of IDUs demonstrates that it is possible to reduce the
  incidence of HCV-infections through improved screening and preventive
  interventions.

 Clinical Infectious Diseases Advance  Access published
August 14, 2012

Gilles
Wandeler1,2,
Thomas Gsponer 2,
Andrea Bregenzer3,
Huldrych F. Günthard4,
Olivier
Clerc5,
Alexandra Calmy6,
Marcel Stöckle7,
Enos Bernasconi8,
Hansjakob
Furrer1,
Andri Rauch1
and the Swiss HIV Cohort Study
1Clinic
for Infectious Diseases, Bern University  Hospital and University of Bern,
Bern,
Switzerland,
2Institute
of Social and Preventive Medicine,  University of Bern, Bern,
Switzerland,
3Cantonal
Hospital, St.Gallen, Switzerland, 4Division
of Infectious Diseases
and
Hospital Epidemiology, University  Hospital Zurich, University of Zurich,
Zurich,
Switzerland,
5University
Hospital Lausanne, Lausanne,  Switzerland, 6University
Hospital
Geneva,
Geneva, Switzerland, 7University
Hospital Basel, Basel, Switzerland, 8Regional
Hospital,
Lugano, Switzerland
1 Comment
Stephen in Birmingham link
10/8/2013 01:37:21 pm

Thanks for sharing the information on hepatitis C. However, I was wondering why you guys haven't posted a new article in a while? This blog has been an amazing resource for me, and I would hate to see that it was finished.

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