Sexual Transmission Of Hepatitis C Virus Research Articles

Hepatitis C Virus Reinfection Among Men Who Have Sex With Men With HIV in New York City.

Hepatitis C virus (HCV) reinfection rates are substantially higher than primary infection rates among men who have sex with men (MSM) with human immunodeficiency virus (HIV) in European cohorts. The behaviors mediating this high rate of transmission among MSM are poorly characterized. We performed a prospective cohort study in New York City (NYC) of MSM with HIV who cleared HCV to determine the incidence of and risk factors for HCV reinfection. We assessed the risk behaviors for primary HCV in NYC: receipt of semen in the rectum, and sexualized methamphetamine use, along with route of use. Multivariable analysis was performed with Andersen-Gill extension of the Cox proportional hazards model. From 2000 through 2018, among 304 MSM with HIV who cleared HCV, 42 reinfections occurred over 898 person-years, for an incidence rate of 4.7 per 100 person-years. Assessing 1245 postclearance visits, only receipt of semen into the rectum was associated with reinfection (hazard ratio, 9.7 [95% confidence interval: 3.3-28.3], P < .001); methamphetamine use was not. The high HCV reinfection rate over almost 2 decades demonstrates that sexual transmission of HCV is not inefficient or unusual and that direct-acting antiviral treatment is not sufficient for HCV elimination among MSM in NYC. The contrasts between both the rates of and risk factors for primary and HCV reinfection suggest that HCV prevalence is highly heterogenous among sexual networks and that sexualized methamphetamine use, rather than mediating transmission, is instead a surrogate marker for the highest HCV prevalence networks. As neither condoms nor treatment have been successful strategies for HCV prevention in NYC, novel interventions are needed to stem this sexually transmitted HCV epidemic.

Incidence of Hepatitis C Virus Infections Among Users of Human Immunodeficiency Virus Pre-exposure Prophylaxis

Sexual transmission of hepatitis C virus (HCV) is well documented among human immunodeficiency virus (HIV)-uninfected individuals. The use of HIV pre-exposure prophylaxis (PrEP) may be associated with engagement in activities that facilitate the transmission of sexually transmitted infections (STIs) and possibly HCV among PrEP users. Between 2012 and 2019, the incidence of HCV and bacterial STIs were calculated among HIV-negative indviduals receiving PrEP at the University Health Network HIV Prevention Clinic.Mucosal, anal, and blood samples were taken to test for HIV, syphilis, and anti-HCV antibodies. Among 344 HIV-uninfected patients receiving PrEP, 86% were men having sex with men (MSM). Five individuals were HCV-antibody positive at the time of PrEP initiation. Serologic and virologic follow-up data were available for 109 HCV-negative individuals over 282 patient-years (PY). Two new infections were recorded, yielding an incidence of primary HCV infection of 0.7 per 100 PY. In contrast with HCV, the incidence rates of chlamydia, gonorrhea, and syphilis were 49.2 per 100 PY, 36.3 per 100 PY, and 5.2 per 100 PY, respectively. Both individuals with new HCV diagnoses reported being MSM with a history of unprotected intercourse and 1 individual also reported recreational drug use. Both individuals were asymptomatic at the time of diagnosis and the infections were detected by routine laboratory monitoring. The low incidence of HCV infections despite significantly higher rates of other STIs suggests that sexual transmission of HCV is uncommon in HIV-negative MSM PrEP users in this community. Performing routine risk-based HCV surveillance among PrEP users should be evaluated. The high incidence of STIs in this population indicates a vital role for periodic STI monitoring in those receiving PrEP.

A212 INCIDENCE OF HEPATITIS C VIRUS INFECTIONS AMONG USERS OF HUMAN IMMUNODEFICIENCY VIRUS PRE-EXPOSURE PROPHYLAXIS

Abstract Background Sexual transmission of hepatitis C virus (HCV) is well-documented among HIV-uninfected individuals. The use of HIV pre-exposure prophylaxis (PrEP) may lead to increased engagement in activities that facilitate the transmission of sexually transmitted infections (STI) and possibly HCV among PrEP users. Aims To assess the incidence of Hepatitis C Virus Infections among HIV negative pre-exposure prophylaxis (PrEP) users Methods Between 2012 and 2019, the incidence of HCV and bacterial STIs were calculated among HIV-negative patients receiving PrEP at the University Health Network HIV Prevention Clinic. Mucosal, anal and blood samples were taken to test for HIV, syphilis, and anti-HCV antibodies. Results Among 344 HIV-uninfected patients receiving PrEP, 86% were men having sex with men (MSM). Five individuals were HCV-antibody positive at the time of PrEP initiation. Serological and virological follow-up was available for 109 HCV-negative individuals over 282 patient-years (PY). Two new infections were recorded, yielding an incidence of primary HCV infection of 0.7/100 PY. In contrast with HCV, the incidence rates of chlamydia, gonorrhea, and syphilis were 49.2/100 PY, 36.3/100 PY, and 5.2/100 PY, respectively. Both individuals with new HCV diagnoses reported being MSM with a history of unprotected intercourse and one also reported recreational drug use. Both individuals were asymptomatic at the time of diagnosis and were detected by routine laboratory monitoring. Conclusions The low incidence of HCV infections despite significantly higher rates of other STIs suggests that sexual transmission of HCV is uncommon in HIV-negative MSM PrEP users. Performing routine risk-based HCV surveillance among PrEP users should be evaluated. The high incidence of STIs in this population indicates a vital role for periodic STI monitoring in those receiving PrEP. Funding Agencies vircan

Syndecan 4 Upregulation on Activated Langerhans Cells Counteracts Langerin Restriction to Facilitate Hepatitis C Virus Transmission.

Sexually transmitted Hepatitis C virus (HCV) infections and high reinfections are a major concern amongst men who have sex with men (MSM) living with HIV-1 and HIV-negative MSM. Immune activation and/or HIV-1 coinfection enhance HCV susceptibility via sexual contact, suggesting that changes in immune cells or external factors are involved in increased susceptibility. Activation of anal mucosal Langerhans cells (LCs) has been implicated in increased HCV susceptibility as activated but not immature LCs efficiently retain and transmit HCV to other cells. However, the underlying molecular mechanism of transmission remains unclear. Here we identified the Heparan Sulfate Proteoglycan Syndecan 4 as the molecular switch, controlling HCV transmission by LCs. Syndecan 4 was highly upregulated upon activation of LCs and interference with Heparan Sulfate Proteoglycans or silencing of Syndecan 4 abrogated HCV transmission. These data strongly suggest that Syndecan 4 mediates HCV transmission by activated LCs. Notably, our data also identified the C-type lectin receptor langerin as a restriction factor for HCV infection and transmission. Langerin expression abrogated HCV infection in HCV permissive cells, whereas langerin expression on the Syndecan 4 expressing cell line strongly decreased HCV transmission to a target hepatoma cell line. These data suggest that the balanced interplay between langerin restriction and Syndecan 4 transmission determines HCV dissemination. Silencing of langerin enhanced HCV transmission whereas silencing Syndecan 4 on activated LCs decreased transmission. Blocking Heparan Sulfate Proteoglycans abrogated HCV transmission by LCs ex vivo identifying Heparan Sulfate Proteoglycans and Syndecan 4 as potential targets to prevent sexual transmission of HCV. Thus, our data strongly suggest that the interplay between receptors promotes or restricts transmission and further indicate that Syndecan 4 is the molecular switch controlling HCV susceptibility after sexual contact.

HIV-1 exposure and immune activation enhance sexual transmission of Hepatitis C virus by primary Langerhans cells.

IntroductionThe significant rise in incidence of Hepatitis C virus (HCV) infection among men‐who‐have‐sex‐with‐men (MSM) living with HIV‐1 suggests that HCV under specific circumstances is transmitted via sexual contact. During sexual transmission HCV has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV remain unclear. We investigated the role of Langerhans cells (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses.MethodsWe investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV‐1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model.ResultsOur data identified an important role for mucosal LCs in facilitating HCV transmission after HIV‐1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV‐1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV‐1 significantly increased HCV transmission by LCs in the ex vivo transmission model. HIV‐1 replication was crucial for the increased HCV transmission as HIV‐1 inhibitors significantly reduced HIV‐1‐induced HCV transmission. Moreover, tissue immune activation of LCs also increased HCV transmission to target cells.ConclusionsThus, our data strongly indicate that HIV‐1 or immune activation in MSM leads to capture of HCV by mucosal LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact.

Sexual transmission of hepatitis C virus among gay and bisexual men: a systematic review.

A systematic review was performed on the evidence of sexual transmission of hepatitis C virus (HCV) in gay and bisexual men (GBM). Studies conducted in industrialised countries and published in English from 2000 to 2015 with data on HCV in GBM were included. Pooled estimates of prevalence and incidence of HCV infection were stratified by study settings and participants' HIV status using random effect models. Case-series reports were summarised descriptively. Of the 38 cross-sectional studies, the pooled HCV prevalence was substantially higher in HIV-positive men (8.3%, 95% CI: 6.7-9.9) than in HIV-negative men (1.5%, 95% CI 0.8-2.1), and higher in those who reported injecting drug use (34.8%, 95% CI 26.9-42.7) than in those who did not (3.5%, 95% CI 2.4-4.5). Of the 16 longitudinal studies, the pooled HCV incidence was markedly higher in clinic-based (7.0 per 1000 person-years, 95% CI 4.6-9.5) than in community-based (1.4 per 1000 person-years, 95% CI 0.7-2.1) studies, and in HIV-positive men (6.4 per 1000 person-years, 95% CI 4.6-8.1) than in HIV-negative men (0.4 per 1000 person-years, 95% CI 0-0.9). Since the early 2000s, 15 case-series reports increasingly pointed to the importance of sexual transmission of HCV in mainly HIV-positive men. Injecting drug use remained the major transmission route of HCV in GBM. Receptive condomless intercourse and concurrent ulcerative sexually transmissible infections are likely drivers that facilitated HCV sexual transmission in HIV-positive men. HCV incidence remains very low in HIV-negative GBM.

Multiple strategies are required to address the information and support needs of gay and bisexual men with hepatitis C in Australia.

Hepatitis C virus (HCV) infection is increasingly reported among gay and bisexual men. However, little is known about the personal and social dimensions of HCV-related experience among these men in Australia. An online survey of 474 Australian gay and bisexual men was conducted from August to December 2013. A subsample of 48 HCV mono-infected and HIV/HCV co-infected men was analysed to explore HCV knowledge, sources of information, unmet information needs and use of HCV-related services. More than half of respondents in the subsample were unaware that HIV infection increases the risk of sexually acquired HCV and most wanted information about how to prevent the sexual transmission of HCV. A majority of respondents requested gay-specific HCV services, and approximately similar proportions of men indicated that they would like these services delivered by a hepatitis organization, a lesbian, gay, bisexual, transgender and intersex (LGBTI) organization and a HIV organization. Men in receipt of HIV antiretroviral treatments were most likely to request that gay-specific HCV information and support services be delivered by a LGBTI or HIV organization (OR = 8.63). These findings suggest that a variety of organizations are required to address the information and support needs of Australian gay and bisexual men with HCV.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.

A comparison of seminal hepatitis C virus (HCV) RNA levels during recent and chronic HCV infection in HIV-infected and HIV-uninfected individuals.

We aimed to characterize seminal hepatitis C virus (HCV) RNA dynamics in human immunodeficiency virus (HIV)-positive men with acute HCV infection given its potential role in sexual transmission of HCV. Men with acute HCV infection (duration, ≤12 months) or chronic HCV infection (duration, >12 months) were prospectively recruited. Paired semen and blood samples were assayed for HCV RNA levels. Results were analyzed using χ(2), Fisher exact, Mann-Whitney U, and Kruskal-Wallis tests. Eighteen men (27.3%) had acute HCV and HIV coinfection, 22 (33.3%) had chronic HCV infection and HIV coinfection, and 26 (39.4%) had chronic HCV monoinfection. HCV RNA was detected in semen specimens from 29 of 66 men (43.9%). The median HCV RNA level in blood was 4.0 log IU/mL higher than that in semen. HCV RNA levels were correlated in semen and blood (r(2) = 0.142). Neither HIV positivity nor acute HCV infection was associated with an increased frequency of seminal HCV RNA detection. Among men with acute HCV and HIV coinfection, the median HCV RNA level in blood specimens from those with seminal HCV RNA was higher than that in blood specimens from those without seminal HCV RNA (P = .001). Seminal HCV RNA was detected in ≥1 sample for 26 of 35 men (74.3%) attending follow up. HCV RNA was detected in semen during both acute and chronic HCV infection. This was unaffected by HIV positivity or the phase of HCV infection. Elevated seminal HCV RNA levels could contribute to sexual transmission of HCV, but other factors, including high-risk behaviors, may be the main drivers for HCV transmission in HIV-infected individuals.

Hepatitis C virus infection among HIV-positive men who have sex with men: protocol for a systematic review and meta-analysis

BackgroundOutbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population.Methods/designEligible studies will include quantitative empirical data related to sexual transmission of HCV in HIV-positive MSM, including data describing incidence or prevalence, and associations between risk factors or interventions and the occurrence or progression of HCV disease. Care will be taken to ensure that HCV transmission related to injection drug use is excluded from the incidence estimates. Scientific databases will be searched using a comprehensive search strategy. Proceedings of scientific conferences, reference lists and personal files will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle–Ottawa scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis.DiscussionHIV-positive MSM are a key HCV-affected population in the US and other high-income countries. This review seeks to identify modifiable risk factors and settings that will be the target of interventions, and will consider how to constitute a portfolio of interventions to deliver the greatest health benefit. This question must be considered in relation to the magnitude of HCV infection and its consequences in other key affected populations, namely, young prescription opioid users who have transitioned to illicit opiate injection, and older injection drug users among whom HCV prevalence and incidence are extremely high. This review is part of a series of systematic reviews and meta-analyses that will synthesize the evidence across all these population groups and develop recommendations and decision tools to guide public health resource allocation.Trial registrationPROSPERO registration number: CRD42013006462

Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV

HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR>2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.

Prevalence of hepatitis C in a Swiss sample of men who have sex with men: whom to screen for HCV infection?

BackgroundWhile the numbers of hepatitis-C-virus (HCV) infections among men who have sex with men (MSM) who are co-infected with the human immunodeficiency virus (HIV) are on the rise, with vast evidence for sexual transmission of HCV in this population, concerns have also been raised regarding sexual HCV-transmission among MSM without HIV infection. Therefore, the aim of this study was to estimate the prevalence of hepatitis C among MSM without HIV diagnosis in Zurich (Switzerland).MethodsParticipants were recruited from a gay health centre and various locations such as dark rooms, saunas and cruising areas in Zurich. Participants self-completed a questionnaire assessing known and suspected risk factors for HCV-infection, and provided a blood sample for detection of past (antibodies) and present (core antigen, RNA) infections with HCV.ResultsIn total, 840 MSM aged 17-79 (median: 33 years) underwent HCV-testing and completed the questionnaire, among whom 19 reported living with HIV. Overall, seven tested positive for HCV-antibodies, and two were also positive for HCV core antigen and HCV-RNA–these two were immigrants, one from a country where HCV is endemic. None of the seven were aware of their infection. The seroprevalence of hepatitis C among the 821 non-HIV-diagnosed MSM was 0.37% (95%-CI: 0.12-1.69%), and one man harboured replicating virus (0.12%; 0.02-0.69%), resulting in a number needed to test of 821 to detect one active infection. Significant univariable associations of lifetime HCV-infection were found with known HIV-diagnosis (OR=72.7), being tattooed (OR=10.4), non-injection use of cocaine/amphetamines (OR=8.8), and non-Swiss origin (OR=8.5). For MSM without HIV-diagnosis, the only variable marginally associated with positive HCV-serostatus was being tattooed (OR=8.3). No significant associations were observed with reported injection drug use, unprotected anal intercourse, sexual practices that may lead to mucosal trauma, or proxy measures for group sex and lesion-prone STIs.ConclusionsOur findings suggest that in Switzerland, hepatitis C among MSM without diagnosed HIV is not more prevalent than in the general population. We found no evidence of elevated rates of sexual transmission of HCV among MSM without HIV-infection. Therefore, we currently see no reason for promoting HCV-testing among all MSM in Switzerland.

Editorial Commentary: Management of Hepatitis C Virus in HIV-Infected Patients in the Era of Direct-Acting Antivirals

Hepatitis C virus (HCV) is a bloodborne pathogen most efficiently transmitted through direct blood-to-blood contact. Injection drug use is the principal route of HCV transmission in developed countries [1]. Although sexual transmission of HCV is uncommon among heterosexual couples in monogamous relationships [2], accumulating evidence suggests that among specific high-risk groups, sexual transmission may be a major route for HCV acquisition. Because HCV and human immunodeficiency virus (HIV) can be transmitted by similar mechanisms, HCV infection is relatively common in HIV-infected patients. In the last decade, an increased incidence of acute HCV infection among HIV-positive men who have sex with men (MSM), attributed to sexual exposure, has been documented worldwide [3, 4]. Incidence rates of acute HCV among HIV-infected MSM in the United Sates range from 0.21 to 0.51 cases per 100 person-years with most cases attributed to injection drug use and high-risk sexual practices [5, 6]. The increasing burden of acute HCV among MSM underscores the urgent need for prevention of HCV transmission among those who remain unexposed as well as evaluation and possibly treatment among those already infected. At the same time, this epidemic provides an opportunity to study early phases of HCV infection that have not been well characterized. HIV/HCV-coinfected patients have been shown to have accelerated liver disease compared to those infected only with HCV, and liver-related complications have become a primary cause of hospitalizations and death in HIV-infected individuals in developed countries [7, 8]. HCV treatment efficacy during the chronic phase of the infection is also reduced in HIV/HCV-coinfected patients when pegylated interferon (peg-IFN) and ribavirin (RBV) are used. Sustained virologic response (SVR) to peg-IFN/RBV is achieved in up to 50% of patients monoinfected with HCV genotype 1, the genotype that is most difficult to treat [9, 10], and by only 14%– 29% of those coinfected with HIV [11, 12]. The approval of the first 2 direct-acting antivirals (DAAs) in 2011, telaprevir (TVR) and boceprevir (BOC), began a new era in the treatment of hepatitis C. Both of these agents are NS3/4A protease inhibitors and were approved only for treatment of HCV genotype 1–monoinfected patients. TVR or BOC, when used in combination with peg-IFN and RBV, achieved SVR rates of ≥70% [13–16]. Uptake of DAA treatment in HCV/ HIV-coinfected individuals has lagged, at least in the United States, largely because their use in this population has not yet been approved by the US Food and Drug Administration. Some concerns also exist regarding potential drug–drug interactions between DAAs and certain antiretrovirals as well as overlappingmedication toxicity. The initial phase 2 pilot studies that evaluated triple therapy in coinfected patients reported significant improvement over treatment with pegIFN and RBV. The addition of a DAA to peg-IFN/RBV therapy increased SVR rates from 45% to 74%, in the case of TVR [17], and from 29% to 63% in the case of BOC [18]. More recently, an IFNsparing 24-week regimen comprised of the NS5B polymerase inhibitor sofosbuvir used in combination with RBV has been studied in HIV/HCV-coinfected patients. Among genotype 1–infected individuals who were also infected with HIV, SVR rates of 76% were achieved Received 18 November 2013; accepted 3 December 2013; electronically published 13 December 2013. Correspondence: Andrew Talal, MD, MPH, Division of Gastroenterology, Hepatology and Nutrition, State University of New York at Buffalo, 875 Ellicot St, Ste 6090, Buffalo, NY 14203 (ahtalal@buffalo.edu). Clinical Infectious Diseases 2014;58(6):880–2 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit804

Identification of host and viral factors involved in a dissimilar resolution of a hepatitis C virus infection

Hepatitis C virus (HCV) transmission from a chronic patient to a susceptible individual is a good opportunity to study viral and host factors that may influence the natural course of hepatitis C infection towards either spontaneous recovery or chronicity. To compare a documented case of a bottleneck event in the sexual transmission of HCV from a chronically infected patient to a recipient host that cleared infection. Host genetic components such as Class I and II HLA and IL28B polymorphism (rs12979860 SNPs) were identified by direct sequencing and LightMix analysis, respectively. Deep nucleotide sequence analysis of quasispecies complexity was performed using massive pyrosequencing platform (454 GS-FLX), and the CD4 specific immune response was characterized by ELISPOT. Sequencing analysis and CD4 response highlighted several NS3-helicase domains in which an interplay between amino acid variability and CD4 immune response might have contributed either to chronicity in the donor patient or to viral clearance in the receptor (newly infected) patient.

The sexual transmission rate of HCV among heterosexual couples

Although hepatitis C virus (HCV) is primarily transmitted by blood-to-blood contact, evidence for sexual transmission of HCV among heterosexual couples remains controversial.1 Therefore, we read with great interest the study by Terrault et al. reporting on a very low risk of sexual transmission of HCV among 500 monogamous heterosexual couples of which the index person was known to be HCV infected.2 Terrault et al. estimated the minimum and maximum heterosexual transmission rate of HCV based on couples from which the partner was infected with a concordant HCV genotype. Unfortunately, interpretation of these study results is not straightforward because of several potential biases. First, in 2.4% of the included couples, the partner had a history of injecting drug use (IDU); in these couples, it is impossible to exclude HCV infection of the partner through sharing injecting equipment. Second, the minimum HCV transmission rate was based on three HCV concordant couples with significant evidence for highly related viral strains. However, two out of three partners within these couples had a history of either IDU, snorting drug use, or sharing snorting equipment, which makes transmission through drug use more likely than sexual transmission. Therefore, this bias will have lead to an overestimation of the HCV incidence rate. Third, although this study has a cross-sectional design, the researchers report it as a cohort study without having measured the HCV infection status and determinants of interest at the beginning of the sexual relationship. To calculate the HCV incidence rate, the researchers assumed that the index cases were HCV infected before the start of their sexual relationship. However, the HCV infection of the index cases might have occurred during the current relationship. This could have resulted in an underestimation of the incidence rate because too many person-years of exposure were included. Fourth, the investigators excluded couples who had a sexual relationship shorter than 36 months, without providing any specific reason. In addition, couples who had less than three sex acts in the preceding 6 months were excluded, even though they could have had many sex acts in the preceding years. These choices may have lead to a selected study population, which might result in a biased estimate of the transmission risk. To conclude, the study by Terrault et al. is subject to several forms of bias that may have had a substantial effect on the results. Most important, because drug-use-related transmission of HCV was not conclusively excluded, this study is likely to have overestimated the incidence rate of heterosexual transmission of HCV among HCV-monoinfected individuals. BART P.X. GRADY, M.D. MARIA PRINS, PH.D. MAARTEN SCHIM VAN DER LOEFF, M.D., PH.D. Cluster of Infectious Diseases Public Health Service Amsterdam, The Netherlands

P3.240 Does the Prevalence of Sexually Transmitted Diseases Adequately Reflect Sexual Transmission of Hepatitis C in the HIV-Infected Population?

BackgroundRecent data suggest sexual transmission of hepatitis C virus (HCV). However, data on the association between HCV and sexually transmitted disease (STD) prevalence are limited.MethodsThis was a retrospective cohort study...

Beyond injecting drug use: investigation of a Victorian cluster of hepatitis C among HIV‐infected men who have sex with men

To examine increased notifications of hepatitis C virus (HCV) in men who have sex with men (MSM) infected with HIV in Victoria, and evaluate HCV transmission risk factors other than injecting drug use. Case series through retrospective review of all HCV cases in Victoria from 1 April 2010 to 30 June 2011, with clinical and laboratory data examined in likely MSM to identify a co-infected cohort. Patients with newly acquired HCV with HIV co-infection were invited to complete a questionnaire exploring novel risk factors for HCV transmission (non-injecting drug use, sexual practices with increased likelihood of trauma, and presence of genital ulcers). Sequencing was performed to determine the local molecular epidemiology of HCV co-infection. Demographics of newly co-infected MSM, traditional versus novel risk factors for HCV acquisition, prior knowledge of potential for sexual transmission of HCV, and association between viral sequences. Thirty-one patients with HIV were identified from 3365 notifications of hepatitis C. The median age was 42 years, and median time from HIV to HCV diagnosis was 22 months. Most patients were asymptomatic, with abnormal liver function tests prompting HCV testing. Interviews with 14 patients identified a high prevalence of novel risk factors and limited knowledge of HCV risk. Two clusters of matching viral sequences were identified. Novel HCV transmission routes have emerged in Victoria. These data reinforce the need for targeted testing and prevention strategies among HIV-infected MSM.

Current Management of Hepatitis C Virus Infection in Patients With HIV Co-infection

As a result of shared routes of transmission, coinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)-infected patients. The prevalence of HIV/HCV coinfection is particularly high among persons who have used injection drugs; however, more recently, sexual transmission of HCV has been recognized among HIV-infected men who have sex with men (MSM). Over the past decade, the effectiveness of HIV treatment improved substantially, leading to a substantial reduction in HIV/AIDS-related deaths; in this context, liver disease due to HCV infection has emerged as major concern for co-infected patients. Over the same period, treatment of HCV remained stagnant, with pegylated interferon alfa (PegIFN) plus ribavirin (RBV; PegIFN/RBV) entrenched as the standard treatment for HCV infection for co-infected patients, who have the greatest risk for liver disease. However, the effectiveness of HCV treatment in this population has been disappointing because of low rates of treatment initiation and success. In 2011, novel HCV NS3/4A PIs (PIs), telaprevir and boceprevir, were approved for use in combination with PegIFN/RBV for the treatment of HCV genotype 1 infection; at the time of approval, important questions regarding the efficacy, safety, and potential for drug interactions with telaprevir and boceprevir had not been answered. More recently, data from drug-interaction studies and 2 small, phase II clinical trials indicate that these HCV treatment regimens may lead to higher rates of HCV eradication in HIV/HCV-coinfected patients, with manageable toxicity and pharmacologic interactions with antiretroviral drugs. As such, these HCV PI-based regimens have emerged as the standard for the treatment of HCV genotype 1 infection in carefully selected HIV-infected patients.

Management of Patients Coinfected With HCV and HIV: A Close Look at the Role for Direct-Acting Antivirals

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients.

Transmission of HCV in HIV-positive populations

The epidemiology of hepatitis C virus (HCV) in HIV has changed significantly over the past decade. This review will outline the current epidemiology of HCV in HIV infection, focusing on the recent changes and factors which have been related to the increase in HCV transmission in HIV-infected men who have sex with men (MSM). Since 2000 there has been recognition in the postindustrialized world that there has been a dramatic rise in the incidence of HCV in HIV-infected MSM. Whereas sexual transmission of HCV remains controversial in the general population, there is increasing evidence that permucosal (sexual and mucosally administered drugs) rather than parenteral risks have become key factors in HCV transmission in HIV-infected MSM. At the most basic level, transmission depends on disruption of a barrier and exposure to infected fluids, usually blood. Whereas transmission factors are often closely entwined, they can be characterized as behavioural and biological factors. With an improved understanding of the epidemiology of HCV in this population, interventions by relevant health authorities could be better focused.