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HCV in MSM, ex-US vs USA Politics/Inner City HCV - Hepatitis C Virus Infections in the Swiss HIV Cohort Study: A Rapidly Evolving Epidemic
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Clin Infect Dis. (Nov 15 2012)
Gilles Wandeler,1,2,a Thomas Gsponer,2 Andrea Bregenzer,3 Huldrych F. Gunthard,4 Olivier Clerc,5 Alexandra Calmy,6
Marcel Stockle,7 Enos Bernasconi,8 Hansjakob Furrer,1 Andri Rauch1,a; and the Swiss HIV Cohort Study
1Department of Infectious Diseases, Bern University Hospital and University of Bern, 2Institute of Social and Preventive Medicine, University of Bern,
3Cantonal Hospital, St Gallen, 4Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich,
5University Hospital Lausanne, 6University Hospital Geneva; 7University Hospital Basel, and 8Regional Hospital, Lugano, Switzerland
from Jules: these authors report on the SWISS Cohort, that about 12,000 screened for HCV, 3.2% of MSMs, 92% of IDUs and 11.3% of heterosexuals were HCV+. then the authors go on to say recent seroconversions of HCV were 3% for MSMs, 33% for IDUs and 1% for heterosexuals, then they say IR for HCV infections increased in MSMs from 0.23 per 100 py in 1998 to 4.09 in 2011, the IR decreased in IDUs....and they conclude: HCV infection 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. The numbers of IDUs with HCV remains gigantic, in the US IDUs and highly maginalized patient populations are a seriously overlooked problem, the elephant in the room, the latest reflection of health disparities for communities of color, the issue that many would like to sweep under the rug, for some its easier to go global oh lets discuss HIV & HCV in undeveloped countries and not pay adequate attention to the USE, lose sight of the issues in the USA, we have an Africa in HIV & HCV in inner cities throughout the USA, shouldnt we be paying adequate attention to solving their problems, and then also helping ex-USA needy, for some its more appealing to forget our inner city problems, at the cost of helping them its easier to help ex-USA, put ex-USA ahead of our inner cities. In the USA we too have a problem that gets little attention, that of HCV infection among HIV+ MSM & HIV- MSM through high risk sexual activity and club drug use & sharing parapanalia, this also needs attention in the USA but gets little, again for some its easier to focus ex-USA, it has a certain panache.
"Of 4629 MSM, 2678 IDU, and 4530 HET screened for HCV infection, 147 (3.2%), 2468 (92.2%), and 513 (11.3%), respectively, had a positive HCV serology at baseline.........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%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion."
"Condom use has declined in recent years in MSM with suppressed HIV load in the SHCS [37], which likely contributes to the increasing incidence of HCV infection in this population. It is crucial that HIV-infected MSM are counseled with regard to the risks of sexual activities that involve traumatic mucosal sex, and that condoms are used consistently during high-risk sexual activity [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 patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS).
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 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET).
Results. HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. 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%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion.
Conclusions. In the SHCS, HCV infection 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 patients infected with human immunodeficiency virus (HIV) [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 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 United States [5-14]. These clusters of HCV infections involved high-risk sexual behaviors 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 among 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 over the past 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 are collected every 6 months.
We assessed changes in the HCV infection incidence in the 3 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.
RESULTS
Baseline Characteristics
Of 4629 MSM, 2678 IDU, and 4530 HET screened for HCV infection, 147 (3.2%), 2468 (92.2%), and 513 (11.3%), respectively, had a positive HCV serology at baseline (Figure 1). A total of 6534 patients, of whom 3333 were MSM, 123 IDU, and 3078 HET, were included in the HCV incidence analyses. Median age at first HCV screening test was slightly higher in MSM (38 years; interquartile range [IQR], 32-44) and HET (36 years; IQR, 30-44), compared to IDU (33 years; IQR, 28-40), whereas MSM were more likely to have a high-level education than patients in the 2 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 with MSM (7.7%) and IDU (8.9%).
HCV Incidence
Over a total follow-up period of 23 707 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, respectively, experienced an HCV seroconversion during follow-up. Between 1998 and 2011, the IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py to 4.09 (95% CrI, 2.57-6.18) in 2011, with 51 cases observed in the last 3 years (Figure 2). There was a similar increase in patients followed in Zurich compared with those in the rest of the country (in 2011, IRs were 2.61 [95% CrI, 1.19-5.13] and 4.10 [95% CrI, 2.18-7.16] per 100 py, respectively). Increases in HCV incidence in MSM were similar when right censoring, midpoint censoring, or interval censoring was used to estimate yearly incidence rates (Supplementary Figure 1).
Hepatitis C virus infection incidence rates by transmission group (shaded: 95% credible intervals). Abbreviations: HET, heterosexual; IDU, injection drug user; MSM, men who have sex with men; py, person-year.
In IDU, the HCV infection IR decreased from 13.89 (95% CrI, 8.20-22.39) per 100 py in 1998 to 2.24 (95% CrI, .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 <0.5 per 100 py, with only 2 cases in 2011 (IR, 0.43 per 100 py [95% CrI, .12-1.29]; Figure 2).
Twenty-five (15.0%) HCV seroconverters had a unique positive serology followed by negative tests. Of those, 6 patients had their HCV infection confirmed by HCV RNA testing within 1 month of the positive serology. In another 8 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 HCV RNA results 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: IR, 0.11 per 100 py [95% CrI, .03-.35]; IDU: IR, 14.36 [95% CrI, 8.36-23.39]; HET: IR, 0.09 [95% CrI, .02-.35]; 2011: MSM: IR, 3.56 [95% CrI, 2.19-5.53]; IDU: IR, 2.42 [95% CrI, .51-13.36]; HET: IR, 0.47 [95% CrI, .14-1.30]).
Predictors of HCV Infection in MSM
Most demographic and behavioral characteristics were similar in HCV seroconverters compared with patients who did not seroconvert (Supplementary Table 1). Median age was 34.9 years in seroconverters and 37.7 years in nonseroconverters, and the proportion of Caucasians was 93% and 92%, respectively. In both groups, >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 (Supplementary Table 1). The incidence of HCV infection 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 with the other patients (Figure 3). In adjusted Cox regression analyses, only inconsistent condom use (adjusted hazard ratio [aHR], 2.09 [95% confidence interval {CI}, 1.33-3.29]) and previous diagnosis of syphilis (aHR, 2.11 [95% CI, 1.39-3.20]) were significantly associated with HCV seroconversion (Table 2).
Hepatitis C virus infection incidence by risk factor in men who have sex with men (shaded: 95% credible intervals). Abbreviation: py = person-year.
Age, education level, CD4+ T-cell count, ART status, and the other variables included in the multivariate model were not significantly associated with the main outcome. Of note, having occasional sexual partners (aHR, 0.97 [95% CI, .56-1.68]) and being followed up in Zurich (aHR, 1.30 [95% CI, .87-1.97]) did not predict HCV seroconversion.
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 cases [19.0%]), 3 (8 cases [12.7%]), and 2 (1 case [1.6%]).
DISCUSSION
We assessed trends in HCV infection incidence between 1998 and 2011 in the main HIV transmission groups in the SHCS. In a population of >6500 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 subpopulation, 50% of all HCV infections occurred in the last 3 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 have described epidemics of HCV infection among HIV-infected MSM [7-12]. Phylogenetic and sociodemographic 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 has increased 18-fold, reaching 4.1 cases per 100 py in 2011. This incidence was higher compared with the large majority of previous studies among HIV-infected MSM reporting estimates lower than 1 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 per 100 py in 2007 [25]. In accordance with 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 United States. However, our study shows that HCV incidence increased similarly outside 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 infection 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 2-fold. 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 2 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 infection 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 HCV, and to screen for syphilis in MSM with acute hepatitis C. Although the use of noninjection drugs has been associated with HCV infections among HIV-infected MSM [28], we found no association between noninjection drug use and HCV seroconversion in MSM. However, we cannot exclude that our analysis underestimates the effect of noninjection 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 with CD4 T-cell counts >200 cells/μL, and most patients (93%) were undergoing ART.
The incidence of HCV infection 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 IDU followed in routine HIV care. Furthermore, Switzerland's long-term heroin prescription program likely contributed to the decreasing incidence of HCV seroconversion 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 IDU, 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 is that we could not estimate the exact HCV seroconversion dates between 2 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 infection. Similarly, the incidence might have been underestimated in patients with late or absent seroconversion, as described by Thomson et al [13]. A further limitation lies in the suboptimal sensitivity and specificity of HCV antibody assays. Although positive ELISA tests were routinely confirmed by immunoblotting, 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 were reduced to 1 year in the SHCS. This should allow for earlier identification of patients with new HCV infections in order to optimize counseling 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 engage in any risk behavior [33-35]. Furthermore, a recent study demonstrated that yearly serological HCV screening and biannual 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 screening every 3 months with liver function tests is cost-effective in settings with HCV incidences >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 behavior, 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 counseling should be performed. Despite the fact that ART is highly efficient in preventing HIV transmission, it does not have any effect on prevention of other sexually transmitted infections. Condom use has declined in recent years in MSM with suppressed HIV load in the SHCS [37], which likely contributes to the increasing incidence of HCV infection in this population. It is crucial that HIV-infected MSM are counseled with regard to the risks of sexual activities that involve traumatic mucosal sex, and that condoms are used consistently during high-risk sexual activity [28]. The example of IDUs demonstrates that it is possible to reduce the incidence of HCV infections through improved screening and preventive interventions.
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