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Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

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Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

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Abstract

Objectives and design: Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. Methods: At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. Results: Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

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... By contrast, HCV prevalence (1.5%) 6 and incidence (0.4/1000PY) 2 in HIV-negative MSM has remained low and similar to that of the general population. However, recent reports from France and the Netherlands identified acute HCV cases in MSM who were using HIV pre-exposure prophylaxis (PrEP), with phylogenetic analysis suggesting genetic similarities to those in HIV-positive MSM 7,8 . ...
... These data, in conjunction with modelling studies, suggest that HCV seroprevalence may stabilise by 2025 and the prevalence of RNA positivity will likely decline 5,29 . Although the epidemic has largely spared HIVnegative MSM, recent reports of PrEP-using cohorts suggest possible bridging of HCV into this community 7,30,31 . In our study, sixteen of 40 (40%) men with AHCV in the clinic cohort were HIV-negative, and most were using PrEP. ...
... This article is protected by copyright. All rights reserved Sexual practices were consistent with those reported previously, with a majority in both groups reporting high risk behaviours 7,8,35 . Interestingly, for both groups, most men (81-83%) thought that some, most or all partners might be HIV-positive, whilst few (13-25%) considered this possibility for HCV. ...
Article
Background and aims: We sought to characterise risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). Methods: MSM with recently-acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Results: Sixteen (40.0%) men in the clinic cohort were HIV-negative MSM. HIV-negative MSM were younger than HIV-positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported non-injection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2-27 sequences; 6 clusters contained HIV-negative and HIV-positive MSM and 1 cluster only HIV-positive MSM. Four of these clusters were part of larger clusters first described in 2007. Conclusions: PrEP-using MSM are at risk of HCV, sharing similar risk factors to HIV-positive MSM. Phylogenetics highlights that PrEP-using and HIV-positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded.
... 2,7 Studies from large cities suggest that HIV-negative MSM could also be at risk for HCV infection, [8][9][10][11][12][13][14] especially those using pre-exposure prophylaxis. [15][16][17][18] However, the evidence is more limited for HIV-negative than HIV-positive MSM, who are regularly screened for HCV. 19 Commercial sex workers are also at risk of STIs, and an increasing HIV burden has been reported among men sex workers (MSW) 20,21 and (male-to-female) trans-women sex workers (TWSW). ...
... 33 The use of drugs before or during sex ("chemsex") in the preceding 12 months was common among MSMs, consistent with a previous national study. 50 The risk of HCV transmission is increased when drugs are injected, known as slamming, 16 Although further studies are needed in Spain, we currently recommend guiding HCV testing individually based on a comprehensive risk assessment, rather than universally screening MSW, TWSW and HIVnegative MSM in the CBVCT setting. ...
... Nevertheless, the high-risk sexual behaviours and the presence of STIs observed in our group of HIVnegative MSM could put them at risk. In fact, an increasing incidence of sexual HCV transmission has been observed in large European, North American and Asiatic cities, although at a lower level than in HIV-positive MSM.[8][9][10][11][12][13][14][15][16] Therefore, it has been suggested that all MSM at high risk (especially those receiving pre-exposure prophylaxis for HIV, or practicing slamming) should be screened for HCV infection and other STIs, and should be the focus of prevention efforts.[8][9][10][11][12]14,[16][17][18]64 ...
Article
Alternative strategies are required to enhance the diagnosis of silent hepatitis C virus (HCV) infections in hard-to-reach key populations at risk. Among them, HCV prevalence and bio-behavioural data is scarce for HIV-negative men who have sex with men (MSM) and men and trans-women sex workers. We sought to describe and assess the potential benefits of a community-based one-step HCV screening and confirmatory strategy for these populations in Barcelona. The screening strategy based on a real-time RT-PCR assay for HCV-RNA detection in dried-blood spots (DBS) was validated and implemented in addition to an antibody point-of-care test in a community centre. HCV prevalence was assessed, and bio-behavioural data was collected. The molecular assay was precise, reproducible, sensitive and specific. Four HIV-negative MSM reported being currently infected (0.75% HCV self-reported prevalence). Implementation of DBS testing was easy, and acceptability was >95%, but no silent HCV case was diagnosed (N = 580). High-risk sexual practices and drug use for sex were reported frequently. HIV prevalence was 4.7% in MSM and 10% in sex workers. Self-reported prevalence of other STIs ranged from 11.3% to 36.2%. In conclusion, HCV-RNA testing in DBS showed a good performance, but the assessed one-step strategy does not seem beneficial in this setting. Although no silent HCV infections were detected, the observed high-risk behaviours and prevalence of other STIs suggest that HCV spread should be periodically monitored among these populations in Barcelona by means of behavioural surveillance, rapid antibody testing and molecular confirmation in DBS. This article is protected by copyright. All rights reserved.
... Permucosal (sexual) HCV exposure (with blood as the medium) seems to facilitate HCV transmission, with risk factors for HCV acquisition including condomless traumatic anal intercourse, higher number of sexual partners, group sex, ulcerative sexually transmitted diseases and sexual acts that involve trauma and bleeding 68,69,73,74,[81][82][83] . The increase in HCV infection incidence has occurred in parallel with certain behavioural trends in MSM communities, including use of social media sexual networking applications, 'serosorting' sexual behaviours (use of HIV serostatus in decision-making regarding sexual behaviour) and the phenomenon of 'chemsex' (illicit drug use, largely methamphetamine, before or during sex by both injecting and non-injecting routes of administration) [83][84][85][86][87][88] , highlighting that HIV-positive MSM and PWID are not mutually exclusive. HIV-positive MSM who inject drugs are at higher risk of HCV acquisition than HIV-positive MSM who do not inject drugs 72 . ...
... Although similar sexual risk behaviours have been reported in HIV-positive and HIV-negative MSM, HCV infection incidence seems to be markedly lower in HIV-negative MSM [89][90][91][92] . However, with increasing use of HIV pre-exposure prophylaxis (PrEP), there is the potential for a reduction in serosorting of sexual partners and increased sexual risk behaviour and transmission of HCV among HIV-positive and HIV-negative MSM populations 83,88,93,94 . Incident HCV infections have been observed in HIV-negative MSM receiving HIV PrEP 92,[94][95][96] . ...
... Incident HCV infections have been observed in HIV-negative MSM receiving HIV PrEP 92,[94][95][96] . Phylogenetic analysis of NS5B sequences obtained from HCV-positive HIV-negative MSM receiving PrEP in Amsterdam (the Netherlands) suggests that HCV transmission is occurring within discrete populations, with MSM-specific HCV clusters containing both HIV-positive and HIV-negative individuals 88 . Although current guidelines do not support routine HCV screening of HIV-negative MSM, the increasing use of HIV PrEP and overlapping behavioural networks support the monitoring of HCV incidence among high-risk MSM to guide policy. ...
Article
The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
... Several Western European countries report high numbers of new HCV infections and re-infections among HIV co-infected MSM, which are mainly driven by ongoing engagement in high-risk behaviour [4][5][6]. Moreover, more reports mentioned the presence of HCV among HIV-negative MSM [7][8][9]. In addition to local transmission, HCV infections can be imported or acquired elsewhere and continue to seed the local epidemic, since viruses do not respect national borders [10]. ...
... The actual HCV prevalence and incidence in this population is, therefore, unknown. Among HIV pre-exposure prophylaxis (PrEP) users in Amsterdam, a high baseline HCV prevalence of 4.8% was found, which was 2.9% in a similar cohort in Antwerp [7,8]. ...
Article
Full-text available
Background: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium. Methods: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold. Results: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available. Conclusion: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.
... One study found an association between chemsex and incident sexually transmitted infections (STIs) in HIV-infected individuals [5]. Another study found an association between chemsex and incident hepatitis C infection in a pre-exposure prophylaxis cohort [6]. Other studies have however questioned how strong the association between chemsex and incident STIs is [1]. ...
... We used routinely collected data that asked clients if they had had condomless-sex under the influence of ecstasy/cocaine/amphetamines/ GHB. Reporting yes to this question was defined as condomless-chemsex even though most studies define chemsex as sex under the influence of a somewhat different list of drugs-mephedrone, γ-hydroxybutyrate (GHB), γ-butyrolactone (GBL) or crystalized methamphetamine [2,5,6]. ...
Article
Full-text available
Background It has been speculated that the prevalence of chemsex is increasing in men who have sex with men and that this may be playing a role in the spread of HIV. Methods We assessed if the prevalence of reported chemsex was increasing and if chemsex was associated with HIV infection in clients attending the ‘Helpcenter’, Antwerp, between 2011 and 2017. This is a HIV/STI testing center that offers HIV/STI testing to HIV-uninfected individuals from key populations including MSM. Results We found an increase in the reporting of condomless sex associated with the use of a number of drugs, including ecstasy, amphetamines, GHB and cocaine in MSM (from 8 to 17%) but not in heterosexuals. Reporting condomless chemsex was associated with HIV infection (adjusted odds ratio 5.7 [95% confidence interval 3.2–10.4]). Conclusions Our findings provide further evidence of the importance of asking MSM clients about the use of psychoactive substances during consultations and tailoring interventions such as pre exposure prophylaxis, more frequent STI screening and substance abuse counseling accordingly.
... One study found an association between chemsex and incident sexually transmitted infections (STIs) in HIV-infected individuals [5]. Another study found an association between chemsex and incident hepatitis C infection in a pre-exposure prophylaxis cohort [6]. Other studies have however questioned how strong the association between chemsex and incident STIs is [1]. ...
... We used routinely collected data that asked clients if they had had condomless-sex under the influence of ecstasy/cocaine/amphetamines/ GHB. Reporting yes to this question was defined as condomless-chemsex even though most studies define chemsex as sex under the influence of a somewhat different list of drugs-mephedrone, γ-hydroxybutyrate (GHB), γ-butyrolactone (GBL) or crystalized methamphetamine [2,5,6]. ...
... Firstly, it should be noted that several relatively small risk groups (e.g. haemodialysis patients, HIV-negative MSM using pre-exposure prophylaxis (PrEP) [45] and asylum seekers or undocumented migrants) were not specifically included in our calculations. Due to their limited size (e.g. ...
... Due to their limited size (e.g. due to the severely lower life expectancy a limited number of haemodialysis patients treated before 1992 is expected to be currently alive, only 376 MSM were participating in a PrEP demonstration project in the Netherlands is 2016 [45]), we do not expect this to majorly influence the overall prevalence. First-generation migrant children under the age of 15 were also not included. ...
Article
Full-text available
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are usually asymptomatic for decades, thus targeted screening can prevent liver disease by timely diagnosis and linkage to care. More robust estimates of chronic HBV and HCV infections in the general population and risk groups are needed. Using a modified workbook method, the total number of ever chronically infected individuals in the Netherlands in 2016 was determined using population size and prevalence estimates from studies in the general and high-risk population. The estimated 2016 chronic HBV infection prevalence is 0.34% (low 0.22%, high 0.47%), corresponding to approximately 49 000 (low 31 000, high 66 000) HBV-infected individuals aged 15 years and older. The estimated ever-chronic HCV infection prevalence is 0.16% (low 0.06%, high 0.27%), corresponding to approximately 23 000 (low 8000, high 38 000) ever-chronic HCV-infected individuals. The prevalence of chronic HBV and HCV infections in the Netherlands is low. First-generation migrants account for most infections with 81% and 60% of chronic HBV and HCV infections, respectively. However, about one-fifth of HCV infections is found in the general population at low risk. This method can serve as an example for countries in need of more accurate prevalence estimates, to help the design and evaluation of prevention and control policies.
... Focussing on the most risky subpopulations and highest-risk techniques may help those most at risk, but it might also create the illusion that lower-risk techniques are completely safe from HCV infection. Tailored prevention messages need to be constantly updated as the transmission dynamics within a risk population change, e.g. when HCV spreads to HIV-negative MSM, presumably because of the protective effect PrEP (pre-exposure prophylaxis) has on the acquisition of HIV [22,23]. Furthermore, addressing only high-risk subgroups may increase the stigma around HCV and indirectly raise a barrier to risk reduction strategies, as it increases avoidance behaviour and prevents free communication and HCV status disclosure [24]. ...
Article
Full-text available
Background Among HIV-infected MSM who have been treated for HCV infection, the HCV reinfection rate is high. It is therefore essential to understand their perceptions of HCV risk behaviour and risk-reducing strategies. Methods This qualitative study among 20 HCV-infected MSM, the majority treated in the era before direct acting antivirals, provides insight into their ideas, motives, and barriers concerning HCV risk reduction, and aims to strengthen prevention strategies for both primary HCV infection and HCV reinfection. Results The strongest motive to implement risk reduction strategies was the reward of avoiding HCV retreatment and its side effects, but this may change with the current implementation of less burdensome HCV treatment. Also, the sexual risk norms in the MSM scene, including social pressure towards risk-taking, HCV stigma, and non-disclosure of HCV status, all form barriers to safe sex. Drug use, strongly present in the context of clubs and group sex, directly impedes the self-efficacy of men to take risk reduction measures. Conclusions Tailored prevention messages, empowerment of self-efficacy for risk reduction, and more insight into risk behaviour over time are ingredients for effective HCV prevention among these men.
... Notably, in our cohort, we did not observe any HCV infections during the follow-up period; however, two of the participants (one PrEP and one PEP user) had been previously infected and spontaneously cleared HCV. This indicates that HCV rates among MSM in our setting are lower than the reported 4.8% HCV prevalence among MSM in PrEP clinics in Amsterdam [21]. ...
Article
Objective: Use of Pre-Exposure Prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence due to decreased condom use among men who have sex with men (MSM). This study examines whether PrEP is associated with STIs in the 12-months following PrEP prescription relative to the 12-months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving Post-Exposure Prophylaxis (PEP). Design: Retrospective cohort study including PrEP users with >12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010-2015 at Clinique l'Actuel (Montréal, Canada). Methods: Incidence of Chlamydia, Gonorrhoea, Syphilis and Hepatitis C Virus over 12-months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate Incidence Rate Ratios (IRRs) with 95% Confidence Intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI screening visits. Models comparing PrEP and PEP users were further adjusted for age and education. Results: 109 PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12-months after PrEP relative to the 12-months prior (IRR: 1.72, CI: 1.22-2.41; aIRR: 1.39, CI: 0.98-1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46-3.24; aIRR: 1.76, CI: 1.14-2.71). Conclusion: Increased rates of STIs among individuals after initiation of PrEP may suggest a greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.
... These outbreaks have been associated with high-risk sexual practices, genital ulcer disease and illicit drug use including parenteral administration [17,158,164,165]. However, a recent study in Amsterdam suggests that HIV-negative MSM may also be at risk of HCV infection, with the same HCV strains already circulating among HIV-positive MSM [166]. In 17 studies (from Australia, Canada, China, Denmark, Italy, Japan, the Netherlands, Spain, Switzerland, Taiwan, the UK and the USA), more than 13,000 HIV-positive MSM were followed for over 91,000 PY between 1984 and 2012; the pooled seroconversion rate was 0.53/100 PY. ...
Chapter
Hepatitis C virus (HCV) infection is a serious public health problem, with globally 71 million people estimated to be chronically infected and at risk of long-term sequelae, including liver cirrhosis and hepatocellular carcinoma [1–3]. Acute infection is typically asymptomatic, and owing to HCV’s ability to evade the immune system, 70–80% of infections become chronic [4–6]. In those chronically infected, it may be decades after initial infection before significant sequelae develop. If left untreated, chronic liver disease will progress to cirrhosis in 5–20%, and 1–5% will die from decompensated cirrhosis or hepatocellular carcinoma [7]. HCV infection contributes to around 27% of liver cirrhosis cases and 25% of primary liver cancers, and resulted in an estimated 400,000 deaths worldwide from these complications in 2015 [1, 8]. Co-infections with HIV are an increasing problem in countries with HIV epidemics in people who inject drugs, and among men who have sex with men, and underlying viral hepatitis is becoming a major cause of death among people with HIV [1, 9].
... It is possible that real time detection of this type of phylogenetic signal could be useful as a trigger to implement more in depth public health monitoring and interventions, such as increasing awareness around risk of sexual transmission of HCV among Table 3. Multivariate logistic regression of factors associated with phylogenetic clustering, including multi-risk profiles, among hepatitis C virus (HCV) Core-E2 sequences (at 5% genetic distance threshold) among participants from five studies of recent HCV infection in Australia GBM [83,84], and tailoring education to individuals based on their HIV infection status [85]. Phylogenetic analysis of HCV NS5B sequences from HIV-negative GBM receiving PrEP in Amsterdam demonstrated GBM-specific HCV clusters containing both HIV-positive and HIV-negative individuals [86]. ...
Article
Full-text available
Introduction Over the last two decades, the incidence of hepatitis C virus (HCV) co‐infection among men who have sex with men (MSM) living with HIV began increasing in post‐industrialized countries. Little is known about transmission of acute or recent HCV, in particular among MSM living with HIV co‐infection, which creates uncertainty about potential for reinfection after HCV treatment. Using phylogenetic methods, clinical, epidemiological and molecular data can be combined to better understand transmission patterns. These insights may help identify strategies to reduce reinfection risk, enhancing effectiveness of HCV treatment as prevention strategies. The aim of this study was to identify multi‐risk profiles and factors associated with phylogenetic pairs and clusters among people with recent HCV infection. Methods Data and specimens from five studies of recent HCV in Australia and New Zealand (2004 to 2015) were used. HCV Core‐E2 sequences were used to infer maximum likelihood trees. Clusters were identified using 90% bootstrap and 5% genetic distance threshold. Multivariate logistic regression and latent class analyses were performed. Results Among 237 participants with Core‐E2 sequences, 47% were in a pair/cluster. Among HIV/HCV co‐infected participants, 60% (74/123) were in a pair/cluster, compared to 30% (34/114) with HCV mono‐infection (p < 0.001). HIV/HCV co‐infection (vs. HCV mono‐infection; adjusted odds ratio (AOR), 2.37, 95% confidence interval (CI), 1.45, 5.15) was independently associated with phylogenetic clustering. Latent class analysis identified three distinct risk profiles: (1) people who inject drugs, (2) HIV‐positive gay and bisexual men (GBM) with low probability of injecting drug use (IDU) and (3) GBM with IDU & sexual risk behaviour. Class 2 (vs. Class 1, AOR 3.40; 95% CI, 1.52, 7.60), was independently associated with phylogenetic clustering. Many clusters displayed homogeneous characteristics, such as containing individuals exclusively from one city, individuals all with HIV/HCV co‐infection or individuals sharing the same route of acquisition of HCV. Conclusions Clusters containing individuals with specific characteristics suggest that HCV transmission occurs through discrete networks, particularly among HIV/HCV co‐infected individuals. The greater proportion of clustering found among HIV/HCV co‐infected participants highlights the need to provide broad direct‐acting antiviral access encouraging rapid uptake in this population and ongoing monitoring of the phylogeny.
... There is evidence from literature that the HCV epidemic is concentrated among HIV-infected MSM [4,26]. However, a recent study from Amsterdam that tested high-risk HIV-uninfected MSM for HCV by HCV antibodies and HCV RNA found a similar HCV prevalence of 4.8% [27]. Given the heterogeneous risk profile of MSM for HCV, and the high costs of HCV RNA-based screening programs, a screening algorithm based on individual risk factors could be a reasonable strategy for the future. ...
Article
Background: The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets. Methods: Between October 2015 and May 2016, we performed a systematic HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA-positive samples. Results: Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92-21.26), unprotected sex with occasional partners (2.01; 1.36-2.98), intravenous drug use (7.13; 4.36-11.64), noninjectable drug use (1.94; 1.3-2.88), and previous syphilis diagnosis (2.56; 1.74-3.76) were associated with HCV RNA positivity. Conclusions: A systematic HCV RNA-based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes.
... From a cohort of 49 HIV-positive and HIV-negative MSM patients with acute hepatitis C infection, we performed phylogenetic analyses of HCV strains based on NS5B sequencing and identified several clusters mixing HIV-positive and HIV-negative patients. Such clusters of HCV infections in MSM had been described for HIV-positive MSM only [3,9,26] but mixed clusters combining HIV-positive and HIV-negative MSM had been previously reported in only one case [27]. In our study, all HCV strains infecting HIV-negative MSM were included in clusters with strains also infecting HIV-positive MSM. ...
Article
Full-text available
The aim of this study was to evaluate the potential transmission of HCV strains between HIV-positive men who have sex with men (MSM) and HIV-negative MSM. Since 2000, an ongoing epidemic of HCV infections is observed among HIV-positive MSM in high-income countries. However, HCV infections in HIV-negative MSM are investigated to a lesser extent due to the lack of follow-up in this population and only limited information is available on the risk of HCV transmission between HIV-positive MSM and HIV-negative MSM. We enrolled 49 MSM of which 43 were HIV-positive and 6 HIV-negative, including 4 being enrolled or waiting for enrolment in a preexposure prophylaxis (PrEP) program. All patients were diagnosed with acute HCV infection at the Infectious Disease Unit at the Hospices Civils de Lyon from 2014 to 2016. Risk factors for HCV infection were similar in both groups and included IV or nasal drug use, and rough sex practices. Typing and phylogenetic cluster analysis of HCV variants were performed by NS5B sequencing. Several clusters of infections were identified (genotype 1a: 3 clusters and 1 pair; genotype 4d: 1 cluster and 2 pairs), suggesting that several transmission events occurred within the study population. Every HCV strain identified in HIV-negative MSM was included in a cluster with HIV-positive MSM. Chronological analysis of contagiousness suggested the transmission of HCV from HIV-positive to HIV-negative patients. We conclude that recommendations for HCV surveillance should not be confined to HIV-positive MSM but should be extended to HIV-negative MSM with similar risk factors.
... All HCV-positive MSM starting PrEP in this study were part of MSM-specific HCV clusters containing MSM with and without HIV. (174) In the UK PROUD study, 5 of 160 (3.1%) men tested more than once for HCV had incident infection (175) and incident infections have been reported in routine clinical PrEP follow up (176).. The most cost-effective strategy for HCV testing among asymptomatic HIV-positive MSM is likely to be annual HCV antibody tests and 3-6 monthly testing of liver function (177). ...
Article
This guideline is intended for use in UK Genitourinary medicine clinics and sexual health services but is likely to be of relevance in all sexual health settings, including general practice and Contraception and Sexual Health (CASH) services, where men who have sex with men (MSM) seek sexual health care or where addressing the sexual health needs of MSM may have public health benefits. For the purposes of this document, MSM includes all gay, bisexual and all other males who have sex with other males and both cis and trans men. This document does not provide guidance on the treatment of particular conditions where this is covered in other British Association for Sexual Health and HIV (BASHH) Guidelines but outlines best practice in multiple aspects of the sexual health care of MSM. Where prevention of sexually transmitted infections including HIV can be addressed as an integral part of clinical care, this is consistent with the concept of combination prevention and is included. The document is designed primarily to provide guidance on the direct clinical care of MSM but also makes reference to the design and delivery of services with the aim of supporting clinicians and commissioners in providing effective services.
... Men who have sex with men Studies from large cities suggest that HIV-negative MSM are also at risk for HCV infection, especially those on pre-exposure prophylaxis (PrEP) [89][90][91][92]. PrEP is effective in reducing the incidence of HIV among people who practise high-risk sexual behaviour, though it does not protect them against other STIs such as HCV. ...
Article
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Background: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a 'Hepatitis C Plan' since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure. Methods: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups. Results: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients. Conclusions: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium.
... Exemplary for this are the very recent observations in an HIV preexposure prophylaxis (PrEP) implementation project in Amsterdam. On entering the PrEP program 15 patients (4%) had detectable HCV RNA [30]. Risk compensation and an increase in the incidence of STD during PrEP use may also occur and could lead to an increase in HCV transmission among PrEP recipients [31]. ...
Article
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Background Direct acting antivirals (DAA) cure 95% of patients infected with hepatitis C (HCV). Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch HIV-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAA became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective acute HCV treatment studies enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the year preceding and following unrestricted DAA availability. We compared the HCV incidence in both years. Results The acute HCV incidence decreased from 93 infections during 8290 person years of follow up in 2014 (11.2/1000 PYFU, 95% CI 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000, 95% CI 4.1–7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% C.I. 0.35-0.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.
... Furthermore, in a recent study a higher HCV prevalence was observed among HIV-negative MSM who started preexposure prophylaxis (PrEP) for HIV infection than previously reported [72]. This resulted in an expanding HCV-epidemic infection regardless HIV status suggesting that routine testing for HIV, HCV and additional sexual transmitted diseases (STDs) should be offered to MSM at high risk for STDs, especially for those receiving PrEP for HIV infection. ...
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Although HIV/HCV co-infected individuals were historically considered a "difficult to treat" population in the era of Interferon (IFN)-based anti-HCV treatment, the introduction of direct-acting antivirals, characterized by excellent efficacy and good safety profile, has widely revolutionized the HCV treatment scenario. Recent real life studies reported excellent sustained virological response rates in HIV/HCV co-infected subjects, thus confirming data obtained in randomized clinical trials. However, certain issues have recently emerged in this population. In fact, high rates of acute HCV infection and reinfections were documented in several studies, particularly in HIV-positive men who have sex with men. Moreover, drug-drug interactions with ART or other co-medications may require careful considerations as well as the management of HIV/HCV co-infected subjects with chronic kidney disease and advanced liver disease in the course of a DAA-based treatment. Hence, we aim to review DAA efficacy studies performed in HIV/HCV co-infected patients in both randomized clinical trials and real-world cohorts. In addition, current challenges and future perspectives are discussed in order to optimize management strategies for HIV/HCV co-infected subjects and their access to care in clinical practice.
... Swedish data showed a similarly low (0.5%) HCV prevalence among HIV-negative MSM in Stockholm in 2013 (7). In contrast, 18/375 (4.8%) of HIV-negative MSM participating in the Amsterdam PrEP (AMPrEP) study tested HCV-positive at baseline in the period August 2015 to June 2016 (8). In IPERGAY 10 participants acquired HCV, while on PrEP, and 5 PROUD participants, which corresponds to an HCV incidence of 1.06 and 1.19 per 100 person years, respectively (9-11) 2 . ...
... Most infections in this group are sexually transmitted and occur in human immunodeficiency virus-1 (HIV) infected MSM. However, recent studies have shown that HIV-negative MSM eligible for or on pre-exposure prophylaxis (PrEP) to prevent HIV acquisition are also at risk of acquiring HCV [6,7]. ...
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To facilitate HCV diagnosis, we developed an HCV-RNA testing service, which involved home-sampled dried blood spots (DBS). The main objective of this study was to evaluate the feasibility of self-sampling at home. Furthermore, to optimise the processing of DBS samples for RNA detection, we evaluated two elution buffers: phosphate-buffered saline (PBS) and L6-buffer. 27 HCV-RNA and 12 HIV-1 RNA positive patients were included. Laboratory spotted DBS (LabDBS) were made by a technician from blood samples drawn at inclusion. Patients received a DBS home-sampling kit and were requested to return their self-sampled DBS (ssDBS) by mail. We compared the RNA load of PBS and L6-eluted labDBS, and of L6-eluted ssDBS, L6-eluted labDBS and plasma. LabDBS load measurements were repeated after 7–13 and 14–21 days to evaluate RNA stability. All 39 plasma samples provided quantifiable RNA loads. In 1/39 labDBS sample, RNA could not be detected (plasma HCV load: 2.98 log10 IU/ml). L6-eluted samples gave a 0.7 log10 and 0.6 log10 higher viral load for HCV and HIV-1 respectively, compared to PBS-eluted samples. Strong correlations were found between labDBS and ssDBS HCV RNA (r = 0.833; mean difference 0.3 log10 IU/mL) and HIV-1 RNA results (r = 0.857; mean difference 0.1 log10 copies/mL). Correlations between labDBS and plasma values were high for HCV (r = 0.958) and HIV-1 (r = 0.844). RNA loads in DBS remained stable over 21 days. Our study demonstrates that self-sampling dried blood spots at home is a feasible strategy for the detection of HCV and HIV-1 RNA. This could facilitate one-step diagnostics and treatment monitoring in communities with high HCV prevalence.
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Background: HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model. Methods: The model was based on epidemiological data from the French Dat'AIDS cohort. Eight risk groups were considered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals, intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence data observed in the cohort between 2012 and 2015. Results: On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosed patients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatment coverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalence among HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCV prevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalence in HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70% would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients would account for 34% of HCV infections in 2026. Conclusions: Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most risk groups, including LR MSM. Elimination in HR MSM will require increased TC.
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The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C virus (HCV) treatment landscape in the last 4 years, providing cure rates over 95% with a shorter duration of treatment and a very good safety profile. This has enabled access to treatment in nearly all HCV infected patients. The launch of two pangenotypic fixed dose combinations (FDCs) in 2017 made a new step forward in HCV treatment by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment. However, retreatment of the few DAA failure patients was still an issue for some HCV genotypes. The launch of the triple regimen FDC, sofosbuvir/velpatasvir/voxilaprevir, solves this issue by providing a cure rate over 96% regardless of HCV genotype. In this review, we describe the current HCV treatment landscape and focus on the development of this triple FDC either in treatment-naïve or treatment-experienced patients with previous failure on a DAA regimen.
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Background: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals (DAAs). Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1) infected patients from Poland will assist in shaping surveillance strategies for HCV. Methods: NS3 and NS5A sequences were obtained from samples of 112 DAA-naive G1 patients (45 G1a, 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. Results: G1a was notably more prevalent compared to G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, p=0.004), AHC cases (46.7% vs. 25.4%, p=0.019) and patients diagnosed with syphilis (52.2% vs. 24.5%, p=0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared to G1b (27.5% vs. 5.2%, p=0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however more common in G1a MSM compared to G1b (50.0% vs. 25.9%, p=0.02). The identified clusters contained sequences originating from up to five Polish cities, located within a mean distance of 370 km. Conclusions: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly AHC patients form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.
Article
Introduction: Broad availability of direct-acting antiviral therapy for hepatitis C virus (HCV) raises the possibility that HCV prevalence and incidence can be reduced through scaling-up treatment, leading to the elimination of HCV. High rates of linkage to HIV care among HIV-infected gay and bisexual men may facilitate high uptake of HCV treatment, possibly making HCV elimination more achievable in this group. Areas covered: This review covers HCV elimination in HIV-infected gay and bisexual men, including epidemiology, spontaneous clearance and long term sequelae in the absence of direct-acting antiviral therapy; direct-acting antiviral therapy uptake and effectiveness in this group; HCV reinfection following successful treatment; and areas for further research. Expert commentary: Early data from the direct-acting antiviral era suggest that treatment uptake is increasing among HIV infected GBM, and SVR rates are very promising. However, in order to sustain current treatment rates, additional interventions at the behavioral, physician, and structural levels may be required to increase HCV diagnosis, including prompt detection of HCV reinfection. Timely consideration of these issues is required to maximize the population-level impact of HCV direct-acting antiviral therapy. Potential HCV transmissions from HIV-uninfected GBM, across international borders, and from those who are not GBM also warrant consideration.
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Introduction: Daily and event-driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event-driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence. Methods: We analysed pooled data from two prospective cohort studies among MSM: Be-PrEP-ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three-monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018. Results and discussion: We included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94). Conclusions: A quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.
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Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.
Article
Background: Men who have sex with men (MSM) are at risk for sexually-transmitted hepatitis C (HCV). Evidence for HCV infection in the context of pre-exposure prophylaxis (PrEP) use in North America is limited. We sought to characterize baseline HCV prevalence and incidence in MSM receiving PrEP in British Columbia (BC), Canada. Methods: We followed individuals in the BC PrEP program from Jan-2018 to Aug-2019. We evaluated baseline prevalence and incident seroconversions (newly positive HCV antibody). A multivariable logistic regression model was performed in MSM for factors associated with HCV prevalence at enrollment, including reported prior sexually transmitted infection (STI), HIV Incidence Risk Index for MSM score, PrEP use due to a partner living with HIV, and location of residence. Results: The median age of the cohort was 33 years, 98.3% male, with 3,058 person years of follow-up. Baseline HCV prevalence was 0.82% (32/3,904 MSM enrollees) and HCV incidence (n=3) was 0.15 per 100 person years (95% CI 0.03 - 0.45). In multivariable analysis, initiating PrEP due to a partner living with HIV (aOR 5.02; 95% CI 1.87 - 13.47) and prior STI (aOR 2.34; 95% CI 1.04 - 5.24) were associated with positive HCV status. Conclusions: Baseline HCV prevalence and incidence was low amongst MSM in a population-based PrEP program in BC, Canada. HCV was associated with bridging from populations living with HIV and evidence of a reported prior STI as a PrEP indicator condition amongst MSM. PrEP initiation may be an opportunity for linkage to HCV screening and treatment.
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Oral pre-exposure prophylaxis (PrEP) has the ability to curb HIV incidence worldwide and bring us closer to ending the HIV epidemic. Scale up of PrEP service delivery has many similar challenges to those faced by voluntary medical male circumcision (VMMC) services roll-out. This article outlines ten important lessons learned during the scale up of VMMC services in sub-Saharan Africa and their application to current oral PrEP implementation efforts to promote faster expansion for public health impact.
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Objective Currently, HIV pre-exposure prophylaxis (PrEP) is not covered by health insurance in the Netherlands. We examined time trends in use of PrEP, characteristics of PrEP users, PrEP eligibility and intention to use PrEP among HIV-negative men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (ACS). Design Prospective cohort study. Methods We used data from four 6-monthly questionnaire waves, collected between 2015–2017. PrEP use over time was examined in logistic regression models using generalized estimating equations. Using descriptive statistics, we compared PrEP users before first-time initiation to non-PrEP-users. We used national guidelines to assess PrEP eligibility. Results We included 687 MSM. Median age was 40 (IQR 33–47) years in 2015. Recent PrEP use was reported by 57/687 (8%) MSM. PrEP use increased over calendar time (P<0.001) to 7% in 2017. PrEP users did not differ from non-PrEP users in socio-demographic characteristics, but reported a significantly higher median number of casual sex partners, more often reported condomless anal sex and chemsex with casual partners, and more often had an sexually transmitted infection in the preceding 6 months (all P<0.05). PrEP eligibility increased over time, but the effect was not statistically significant (P = 0.075). PrEP eligibility criteria were met by 149/460 (32%) at wave 4, of whom 31/149 (21%) reported use of PrEP. The proportion with a high intention to use PrEP was greater among eligible than non-eligible MSM (51% vs. 24%, P<0.001). Conclusion PrEP use increased over time but remained under 10%, even though 32% met the eligibility criteria, of whom 51% had a high intention to use PrEP. This suggests that a large proportion of Dutch MSM at risk could benefit from PrEP.
Article
Background: The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018. Methods: A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses. Results: Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69-1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12-0.71) per 100 PYFU in 2010-2012 to 1.93 (95% CI 1.36-2.67) in 2016-2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006-2009, and recent syphilis acquisition. Conclusions: An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour.
Article
Objectives Micro‐elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co‐infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro‐elimination in HIV‐treated cohorts, few have considered HCV micro‐elimination among those not treated for HIV or at a national level. Methods Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV‐diagnosed individuals, up to the end of 2017. Results Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15–10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59–8.15). Conclusions Our data demonstrate that micro‐elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co‐infected, including those not being treated for their HIV.
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Background Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. Methods We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. Results Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1–0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4–0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019–3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. Conclusions Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.
Article
Purpose of review: The scale-up of direct-acting antiviral (DAA) therapy and introduction of preexposure prophylaxis (PrEP) has changed the epidemiology of sexually acquired hepatitis C virus (HCV) amongst HIV-positive and HIV-negative MSM. Recent findings: Sexually acquired HCV continues to occur predominantly amongst HIV-positive MSM. Despite an increased uptake of DAA therapy the incidence of acute HCV has not declined consistently amongst HIV-positive MSM, likely a result of high infection and reinfection rates. Increasing cases of sexually acquired HCV have been reported amongst HIV-negative MSM accessing PrEP. Despite a lower prevalence of HCV at baseline, HIV-negative MSM accessing PrEP have an equally high overall incidence of HCV compared with HIV-positive MSM during follow-up. Behavioural factors (high-risk sexual behaviours and sexualized drug use) appear to be driving this HCV epidemic amongst MSM and effective behavioural interventions and early identification of reinfections are essential to control the HCV epidemic amongst MSM. Summary: An improved understanding of the epidemiology of sexually acquired HCV will allow implementation of more effective public health interventions to control the transmission of HCV amongst HIV-positive and HIV-negative MSM.
Article
Hepatitis C virus is a global public health threat, affecting 71 million people worldwide. Increasing recognition of the impact of this epidemic and recent advances in biomedical and technical approaches to hepatitis C prevention and cure have provided impetus for the World Health Organization (WHO) to call for global elimination of hepatitis C as a public health threat by 2030. This work reviews the feasibility of hepatitis C elimination and pathways to overcome existing and potential future barriers to elimination. Drawing on cost-effectiveness modeling and providing examples of successful implementation efforts across the globe, we highlight the resources and strategies needed to achieve hepatitis C elimination. A timely, multipronged response is required if the 2030 WHO elimination targets are to be achieved. Importantly, achieving hepatitis C elimination will also benefit the community well beyond 2030.
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HIV negative men who have sex with men (MSM) who access pre‐exposure prophylaxis (PrEP) report sexual behaviours that could place them at high risk of hepatitis C virus infection (HCV). We report HCV prevalence and incidence from the PROUD trial of PrEP.PROUD was an open‐label, wait‐list design randomised trial of HIV PrEP for MSM.Participants were recruited between November 2012 and April 2014, and follow‐up continued to October 2016. Initial HCV testing followed national guidelines, with screening “on indication”, but was replaced by routine quarterly screening in the latter part of the study.We estimated HCV seroprevalence at enrolment and incidence overall and according to calendar year.544 participants were recruited to PROUD. 133 (24.4%) were screened for HCV at enrolment, and 490 (90.1%) were tested at least once during follow‐up. Seroprevalence at enrolment was 2.1% (11/530; 95% CI: 1.0‐3.7%). Median follow‐up time was 2.6 (IQR: 2.1‐3.0) years and total follow‐up of 1188.8 person years (PY). Twenty‐five participants had a new HCV infection during the trial, yielding an incidence rate of 2.1 per 100 PY (25/1188.8; 95% CI: 1.4‐3.1), of which three were re‐infections. There was some evidence that HCV incidence increased over calendar time (P‐value for trend=0.09), reaching an estimated 4.0 per 100 PY (95% CI: 2.0‐8.1)in 2016. In conclusion, participants in PROUD had a high, and possibly increasing, incidence of HCV infection. This high incidence of HCV supports the 2018 BHIVA/BASHH recommendation for quarterly HCV testing among HIV‐negative MSM using PrEP in the UK.
Article
Emerging data from Europe have documented increases in diagnoses of acute hepatitis C virus (HCV) infection among HIV-negative men who have sex with men. We investigated risk factors for HCV and their correlates in the Together 5000 study, a U.S. national cohort study of HIV-negative men (n = 6089), transgender women (n = 40), and transgender men (n = 42) who have sex with men. We used bivariate and multivariable analyses to determine demographic and behavioral factors associated with high risk for acute HCV infection (using the HCV-MOSAIC risk indicator with a score ≥ 2.0). Mean HCV risk score was 1.38 (SD = 1.09) and 27.3% of participants had HCV risk scores ≥ 2.0. In multivariable modeling, being cisgender male (vs. not) was associated with having a lower HCV-MOSAIC risk score. Meanwhile, being white, having been incarcerated, prior use of HIV pre- or post-exposure prophylaxis, having ever been tested for HIV, and recent methamphetamine use were associated with high risk for HCV. More than one-in-four participants exceeded the threshold score for HCV risk. Those with high HCV-MOSAIC risk scores were more likely to have been in settings where they could be tested for acute HCV (i.e., HIV testing, PrEP care, PEP care, incarceration), suggesting opportunities to engage them in HCV screening, prevention, and treatment.
Thesis
The two RNA viruses HIV and HCV are getting a lot of public health concerns because both of them have overlapping risk factors for transmission through direct blood and sexual contacts. Furthermore, HIV and HCV infections are the leading cause of mortality and morbidity globally due to related diseases. However, with the introduction of antiretroviral therapy (ART) for the treatment of HIV infection and direct-acting antivirals (DAAs) for the treatment of HCV infection, patients infected by these viruses are witnessing significant improvement in their quality of life. However, the high replication rate and the lack of error correction mechanism of these viruses result in a diverse viral population referred to as quasispecies. Under drug- selective pressure, the viral quasispecies select resistance variants against corresponding drug and render the therapy ineffective especially in cases an appropriate treatment monitoring is not ensured.To reserve a wide range of possibilities for a life-long ART in HIV-infected patients and in parallel to reduce cost for treatment of both HIV and HCV infection, research focusing on detection, surveillance and transmission of resistance mutations is fundamental to prevent treatment failure on antivirals. In this PhD, we employed the ultra-deep sequencing (UDS) or next-generation sequencing (NGS) technologies to look for minority resistant variants (MiRVs) which are conventionally considered to represent less than 15%-25% of viral population and undetectable by Sanger sequencing. The presence of MiRVs at baseline is possibly responsible for the treatment failure and their presence at failure may limit options for subsequent therapies. In this PhD, we evaluated the prevalence and clinical impact of MiRVs on integrase gene in HIV-infected patients failing an integrase inhibitor containing regimen. We also evaluated the impact of MiRVs in HCV genotype 3 and genotype 4-infected patients failing DAAs. Furthermore, we used the UDS technique to identify and characterize the HCV transmission networks among a key population of men having sex with men either co-infected with HIV or at high risk of HIV acquisition. We also discovered several cases of mixed HCV genotype infections in this population probably for their high risk of multiple HCV exposures. The advantages of UDS in virology research and the applicability of this technique in clinic have been questioned and verified throughout multiple types of projects in this PhD. UDS has not been conclusively established to be more interesting and beneficial than Sanger sequencing in prevention of treatment failure in patients infected by HIV or HCV and in identifying the viral transmission networks at large scale if taking into account the experiment cost and time for data analysis. However, the dynamic development of UDS technologies and the continuing attempts in optimizing analysis procedures display a promising role of UDS. And the applicability of UDS in clinical practice still needs to be elucidated in different kinds of research projects.
Article
Background: PrEPX was an Australian HIV pre-exposure prophylaxis (PrEP) study conducted between 2016 and 2018. This analysis aimed to estimate hepatitis C (HCV) incidence and explore likely modes of transmission. Setting: Cohort study of PrEP users in Victoria, Australia. Methods: HCV tests were conducted at enrolment and every 12 months thereafter. HCV incident cases were identified from laboratory data. Likely modes of transmission were inferred from computer-assisted self-interviews (CASI), medical records, and interviews. Results: Among 3,202 PrEPX participants tested for HCV at baseline, HCV RNA-positive prevalence was 0.22% (95% CI 0.09-0.45). Among participants testing HCV antibody- or RNA-negative at baseline, 2,058 had at least one follow-up HCV test. Eight incident HCV cases were identified during 2,111 person-years of follow-up (incidence 0.38/100 person-years); all were primary infections in men who had sex with men (MSM). Clinical, laboratory and CASI data were available for all, and six cases were interviewed. Three cases were attributable to injecting drug use (IDU). A fourth case reported IDU, but his HCV was attributable to sexual transmission. Four other cases reported no IDU and probably acquired HCV sexually. Most cases reported anal trauma in the context of condomless receptive anal intercourse during group sex at sex-on-premises venues (SOPV). Conclusion: Incident HCV was uncommon in PrEPX compared to international PrEP studies, and most cases were transmitted sexually. Our findings highlight the need for HCV prevention messaging by clinicians, in SOPV and on digital platforms utilised to arrange group sex, and for HCV screening among some PrEP-using MSM.
Article
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The advent of direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment, with most recent trials demonstrating high efficacy rates (>90%) across all genotypes and special populations, including patients with HIV/HCV coinfection. The efficacy rates of HCV treatment are nearly identical between patients with HCV monofection and patients with HIV/HCV coinfection; however, there are limited studies to compare real-world efficacy with efficacy observed in clinical trials. Using a database from HIV clinics across the United States (US), we identified 432 patients with HIV/HCV coinfection who completed DAA therapy from January 1, 2014 to March 31, 2017 and were assessed for efficacy. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion; furthermore, factors associated with achieving SVR12 were identified. In this analysis, we found DAA therapies to be effective, with 94% of the patients achieving SVR12 and 6% experiencing virologic failure. Baseline variables, including older age, HCV viral load <800K IU/ML, FIB-4 score <1.45, absence of depression, diabetes, substance abuse, and use of DAA regimens without ribavirin were significant predictors of achieving SVR12. Patients with fewer comorbidities, better liver health, and lower HCV viral loads at baseline were more likely to achieve treatment success. Our results were consistent with other real-world studies, supporting the use of HCV therapy in HIV/HCV coinfected patients.
Article
Objectives To calculate the rate of hepatitis C virus (HCV) among HIV-infected men who have sex with men (MSM) with no reported history of injection drug use (IDU), and to assess whether disparities exist in HIV/HCV coinfection by race/ethnicity and neighbourhood poverty level within this population in New York City. Methods HIV-positive men who reported sex with men and did not report IDU at the time of HIV diagnosis, diagnosed through 2015 and alive as of 2000, were matched to people with HCV first reported to the New York City Department of Health and Mental Hygiene between 2000 and 2015. Those with HCV reported before or within 90 days of HIV infection were excluded. A multivariable Cox proportional hazards model was fit to compare the association between HCV diagnosis, race/ethnicity and neighbourhood poverty level. Results From 2000 to 2015, 54 488 non-IDU MSM were diagnosed with HIV, of whom 2762 (5.1%) were diagnosed with HCV after HIV diagnosis, yielding an overall age-adjusted HCV diagnosis rate of 512 per 100 000 person-years. HIV/HCV coinfection was significantly higher among non-Latino blacks (adjusted HR (aHR)=1.24, 95% CI 1.11 to 1.40) compared with non-Latino whites and among persons living in high-poverty neighbourhoods compared with those in low-poverty neighbourhoods (aHR=1.17, 95% CI 1.01 to 1.35) after stratification by year of HIV diagnosis. Conclusion Disparities in HIV/HCV coinfection among HIV-positive MSM were observed by race/ethnicity and neighbourhood poverty level. Routine HCV screening is recommended for people infected with HIV. People coinfected with HIV and HCV should be linked to HCV care, treated and cured to reduce morbidity and mortality, and to avoid ongoing HCV transmission.
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Purpose of review: The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. Recent findings: With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. Summary: Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
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Introduction: Pre-Exposure Prophylaxis (PrEP) is highly effective in reducing the risk for HIV infection among men who have sex with men (MSM) and may have an important impact in slowing down the HIV epidemic. Concerns remain however about low adherence, increased risk behaviour and reduced condom use when using PrEP. The aim of this study was to assess these factors prospectively among MSM using daily and event-driven PrEP in Belgium. Methods: An open-label prospective cohort study was conducted from October 2017 to May 2018 at the Institute of Tropical Medicine, in Antwerp, Belgium. At enrolment, MSM at high risk for HIV chose between daily or event-driven PrEP. They were allowed to switch regimens or stop taking PrEP at each of their tri-monthly visits. Data were collected on an electronic case report form, web-based diary and self-administered questionnaire. Screening for HIV and other Sexually Transmitted Infections (STIs) was also performed. Results: Two hundred MSM were followed up for a total duration of 318 person-years. At month 18, 75.4% of the participants were on daily and 24.6% were on event-driven PrEP. The mean proportion of covered sex acts by PrEP for the complete follow-up period was 91.5% for all participants, 96.5% for daily and 67.0% for event-driven PrEP use. The number of casual and anonymous sex partners was significantly higher for daily users, as compared with event-driven users, but did not change over time. In contrast, the mean proportion of condomless receptive anal intercourse with casual and anonymous partners increased significantly during follow-up, for both daily and event-driven use (p < 0.0001 for all 4 trends). No new HIV infection was diagnosed during follow-up. The incidence of bacterial STIs was 75.4 per 100 person-years (95% CI 63.8 to 89.1). We did not detect a significant change in N. gonorrhoeae/C. trachomatis incidence over time. The incidence of hepatitis C was 2.9 per 100 person-years. Conclusions: PrEP is an effective and well adopted HIV prevention tool for MSM in Belgium. Participants adapted daily and event-driven regimens to their own needs and were able to adapt their PrEP adherence to risk exposure.
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Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported.
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Introduction: Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment. Methods: We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports. Results and discussion: Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis. Conclusions: High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.
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In May 2016, the World Health Organization adopted the first global hepatitis strategy, setting the ambitious goal of “elimination of viral hepatitis as a public health threat” by 2030. HCV-specific targets included a 65% reduction in HCV-related mortality and an 80% reduction in HCV incidence. Globally, an estimated 71 million people were living with chronic HCV infection in 2015. Approximately two million new HCV infections occur annually, with injecting drug use and unsafe health-care practices (including unsterile health-care injection), the predominant modes of HCV transmission.
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Increases in hepatitis C (HCV) infections among gay and bisexual men have recently been reported in a number of countries, with sexual transmission being the primary route of infection. Given that in countries such as Australia most gay and bisexual men living with HIV are already engaged in clinical care – as are an increasing number of HIV-negative men – there is potential for reducing onward HCV transmission through proactive testing and treatment. This study explored knowledge, attitudes and practices related to HCV among 194 gay and bisexual men collected through an online survey in Australia. Overall, respondents had high levels of HCV knowledge; however, only 76% knew about the availability of new treatments for HCV. Men’s knowledge of their own HCV testing history was uncertain, with one in six unaware if they had ever been tested. Among men who reported recent drug injecting, one-third had been injected by someone else, and two-thirds had injected someone else, indicating a subculture of cross-administering within sexualised drug-use networks. We argue that the robust sexual, socio-cultural and clinical infrastructure that has been developed by – and for – gay and bisexual men around HIV care and prevention creates the potential for reducing HCV in this group.
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Background and aim: Related research has found that men who visit public sex environments such as a gay bathhouse engage in unprotected anal intercourse and tend to have multiple sexual partners during their visit. We aimed to assess the risk of hepatitis C virus (HCV) transmission among men attending a gay bathhouse. Methods: A prospective study of the prevalence of HCV among men attending a gay bathhouse was conducted in Bangkok, Thailand, from October 2019 to March 2020. HCV risks and risk perceptions were evaluated using a self-administered questionnaire. HCV testing with result notification was provided on site. Results: Of the 40 participants (median age 30 years), one subject (2.5%) was positive for HCV antibody. Bathhouse patrons reported engaging in high-risk sexual behavior, including sexually transmitted infection history and Chemsex experience. The subject tested positive for HCV antibody reported a frequency of attending gay bathhouse of around 2-4 times monthly and had multiple partners while attending a gay bathhouse. Only 15% of subjects realized that hepatitis C can be transmitted through sexual intercourse. Conclusion: Our findings support HCV transmission-reducing guidelines recommending providing selective HCV testing among men who have sex with men (MSM). Bathhouse patrons reported low literacy levels on HCV transmission. Nevertheless, HCV screening should cover a population exhibiting high-risk sexual behaviors such as attending a gay bathhouse.
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The role of condomless anal intercourse (CAI) as a driver for the epidemic of hepatitis C in MSM is still debated. Timely access to direct‐acting antivirals (DAA) could represent an essential strategy to tackle this. Case notes of MSM diagnosed with acute hepatitis C (AHC) between July 2016 and June 2017 in a sexual health clinic in London were included. Behavioral data on sexual practices and STI monitoring in the 6 months prior to AHC diagnosis were collected. DAA routes of access and timing from AHC diagnosis to start of treatment were analyzed. 60 individuals were enrolled (median age 39 years, IQR=33‐46, 62% HIV co‐infected, 72% genotype 1a). CAI was reported by 97%, drug use prior to or during sex by 73%; 46% were diagnosed with a rectal STI and 29% with syphilis. 37% did not report any HCV risk factors other than condomless anal sex. 36% had a new rectal STI in the 6 months following AHC. 82% accessed DAA treatment and median time from AHC to DAA start was 278 days for those following the NHS standard of care route, 132 days for those accessing DAA via participation in trials and 114 for those who had self‐sourced DAA online (p<0.0011). SVR12 was achieved in 100% of the patients who received DAA treatment.In conclusion, CAI is a significant risk factor for HCV acquisition in MSM, irrespective of their HIV status. Rapid and wider access to treatment with DAA could represent a powerful strategy to reduce onward transmission and risk of reinfection in MSM. This article is protected by copyright. All rights reserved.
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Introduction: The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated. Finally, antiviral activity, safety and potential for drug interactions in phase II/III clinical trials in distinct patient populations are discussed. Expert opinion: The triple co-formulation of sofosbuvir-velpatasvir-voxilaprevir represents a major step towards HCV eradication. It depicts high efficacy even in patients infected with viruses harboring resistance-associated substitutions (RAS), including those selected after DAA failures. Likewise, very high success rates and good tolerance are seen in special patient populations, including decompensated cirrhotics, HIV coinfection, organ transplantation or renal insufficiency. A pill once daily for 8 weeks gives SVR rates above 95%. In prior DAA failures, extending treatment to 12 weeks maximizes SVR rates.
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Background: Hepatitis B (HBV), hepatitis C (HCV) and other sexually transmitted infections (STIs) have been associated with HIV transmission risk and disease progression among gay men and other men who have sex with men (MSM), but the frequency and distribution of STIs in this community in Canada has not been extensively studied. Methods: We recruited MSM living with and without HIV from a large primary care clinic in Toronto. Participants completed a detailed socio-behavioural questionnaire using ACASI and provided blood for syphilis, HIV, HBV and HCV, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and human cytomegalovirus (CMV) serology, urine for chlamydia and gonorrhea, and a self-collected anal swab for human papillomavirus (HPV) molecular diagnostics. Prevalences were expressed as a proportion and compared using chi-square. Results: 442 MSM were recruited, 294 living with HIV and 148 without. Active syphilis (11.0% vs. 3.4%), ever HBV (49.4% vs. 19.1%), HCV (10.4% vs. 3.4%), HSV-2 (55.9% vs. 38.2%), CMV (98.3% vs. 80.3%) and high-risk (HR) anal HPV (67.6% vs. 51.7%) infections were significantly more common in men living with HIV. Chlamydia and gonorrhea were infrequent in both groups. Regardless of HIV infection status, age and number of lifetime male sexual partners were associated with HBV infection and lifetime injection drug use with HCV infection. Conclusions: Syphilis and viral infections, including HBV, HCV, HSV-2, CMV, and HR-HPV, were common in this clinic-based population of MSM in Toronto and more frequent among MSM living with HIV. This argues for the implementation of routine screening, vaccine-based prevention, and education programs in this high-risk population.
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Background. Sexual transmission of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is an emerging issue. Studies addressing the temporal trends and risk factors associated with incident HCV in HIV-infected MSM in the community-based primary care settings in the United States are scarce. Methods. Using a retrospective cohort study design, HCV incidence, defined as HCV antibody seroconversion, was determined in 1147 HIV-infected men receiving care at Chase Brexton Health Care clinics in Baltimore, Maryland between 2004 and 2014. Multivariate regression analyses were used to identify factors associated with incident HCV. Results. There were 42 incident HCV infections during 5242 person-years (PY) of follow up (incidence rate [IR], 8.01/1000 PY). Thirty-seven (88%) of the incident infections were in MSM, of whom 31 (84%) reported no injection-drug use (IDU). The annual IRs for MSM were 13.1–15.8/1000 PY between 2004 and 2007, decreased to 2.7–6.2/1000 PY between 2008 and 2011, and increased to 10.4/1000 PY and 13.3/1000 PY in 2013 and 2014, respectively. Injection-drug use was strongly associated with incident HCV among all MSM (IR ratio [IRR], 14.15; P = .003); however, among MSM without IDU, entering care between 2010 and 2013 (IRR, 3.32; P = .01), being employed (IRR, 3.14; P = .03), and having a history of ulcerative sexually transmitted infections (IRR, 3.70; P = .009) or of polydrug use (IRR, 5.54; P = .01) independently predicted incident HCV. Conclusions. In this cohort of HIV-infected men, a re-emerging HCV epidemic was observed from 2011 to 2014 among MSM. In addition to IDU, high-risk sexual behaviors, favorable socioeconomic status, and polydrug use fueled this increase in HCV infections.
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Sexually acquired hepatitis C virus (HCV) infection remains a public health problem with significant disease burden primarily in HIV-positive men who have sex with men (MSM). Over the past decades, the epidemic of sexually transmitted HCV infection has continued to expand and the epidemiology of HCV in HIV has changed significantly. In the post-combination antiretroviral therapy era, sexual network characteristics within the specific core group of MSM with increased sexual risk behaviours including serosorting on the basis of HIV-positive status and intense mucosally traumatic sexual practices confer increased HCV acquisition and transmission. This review summarizes the current epidemiology of sexually acquired HCV infection and the clinical and immunological contexts of acute HCV infection, and describes the biological, social and behavioural factors that have facilitated permucosal transmission of HCV in MSM. While the advent of direct-acting antivirals significantly improves treatment responses, sexually transmitted HCV reinfections occur in a substantial proportion of HIV-positive MSM following clearance of a primary infection. Effective strategies and preventive interventions that are tailored to the MSM communities cannot be overemphasized to facilitate control of sexually acquired HCV infection.
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Background: Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. Methods: The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). Results: The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees. Conclusions: The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective. Trial registration: Current Controlled Trials ISRCTN94465371 . Date of registration: 28 February 2013.
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Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV.
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Background: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. Methods: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. Results: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). Conclusions: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).
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Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0–52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63–15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04–12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02–6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27–192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39–8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19–2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60–14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.
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Sequencing is important for understanding the molecular epidemiology and viral evolution of hepatitis C virus (HCV) infection. To date, there is little standardisation among sequencing protocols, in-part due to the high genetic diversity that is observed within HCV. This study aimed to develop a novel, practical sequencing protocol that covered both conserved and variable regions of the viral genome and assess the influence of each subregion, sequence concatenation and unrelated reference sequences on phylogenetic clustering analysis. The Core to the hypervariable region 1 (HVR1) of envelope-2 (E2) and non-structural-5B (NS5B) regions of the HCV genome were amplified and sequenced from participants from the Australian Trial in Acute Hepatitis C (ATAHC), a prospective study of the natural history and treatment of recent HCV infection. Phylogenetic trees were constructed using a general time-reversible substitution model and sensitivity analyses were completed for every subregion. Pairwise distance, genetic distance and bootstrap support were computed to assess the impact of HCV region on clustering results as measured by the identification and percentage of participants falling within all clusters, cluster size, average patristic distance, and bootstrap value. The Robinson-Foulds metrics was also used to compare phylogenetic trees among the different HCV regions. Our results demonstrated that the genomic region of HCV analysed influenced phylogenetic tree topology and clustering results. The HCV Core region alone was not suitable for clustering analysis; NS5B concatenation, the inclusion of reference sequences and removal of HVR1 all influenced clustering outcome. The Core-E2 region, which represented the highest genetic diversity and longest sequence length in this study, provides an ideal method for clustering analysis to address a range of molecular epidemiological questions.
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Background: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.
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The epidemiology of the incidence of sexually transmitted hepatitis C virus (HCV) infection in HIV-positive MSM is only partially understood. In the presence of HIV, HCV infection is more likely to become chronic and liver fibrosis progression is accelerated. A systematic review and meta-analysis was used to synthesize data characterizing sexually transmitted HCV in HIV-positive MSM. Electronic and other searches of medical literature (including unpublished reports) were conducted. Eligible studies reported on HCV seroconversion or on reinfection postsuccessful HCV treatment in HIV-positive MSM who were not injecting drugs. Pooled incidence rates were calculated using random-effects meta-analysis, and meta-regression was used to assess study-level moderators. Attributable risk measures were calculated from statistically significant associations between exposures and HCV seroconversion. More than 13 000 HIV-positive MSM in 17 studies were followed for more than 91 000 person-years between 1984 and 2012; the pooled seroconversion rate was 0.53/100 person-years. Calendar time was a significant moderator of HCV seroconversion, increasing from an estimated rate of 0.42/100 person-years in 1991 to 1.09/100 person-years in 2010, and 1.34/100 person-years in 2012. Reinfection postsuccessful HCV treatment (n = 2 studies) was 20 times higher than initial seroconversion rates. Among the seroconverters, a large proportion of infections were attributable to high-risk behaviours including mucosally traumatic sex and sex while high on methamphetamine. The high reinfection rates and the attributable risk analysis suggest the existence of a subset of HIV-positive MSM with recurring sexual exposure to HCV. Approaches to HCV control in this population will need to consider the changing epidemiology of HCV infection in MSM.
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To the Editor—Although hepatitis C virus (HCV) is most efficiently transmitted through percutaneous routes, sexual transmission of HCV is well documented among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) [1–4]. Sexual transmission of HCV also occurs among HIV-uninfected MSM [5, 6], with many reporting sexual contact with HIV-infected partners [7]. The Centers for Disease Control and Prevention recommends the use of preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate for the prevention of HIV infection among at-risk MSM, with screening for HCV prior to PrEP initiation [8]. However, ongoing monitoring for HCV infection among PrEP users is not recommended. Here, we report on 2 incident HCV infections diagnosed among 485 HIV-uninfected MSM receiving PrEP at the Kaiser Permanente San Francisco Medical Center between February 2011 and December 2014. These infections occurred during 304 person-years of PrEP use, for an incidence rate of 0.7 per 100 person-years (95% confidence interval, .08–2.4). Patient 1 was a 46-year-old MSM who initiated PrEP in August 2013. From August 2013 through July 2014, he was diagnosed with 2 episodes of syphilis, rectal gonorrhea, and rectal chlamydia. In June 2014, the patient reported receptive anal intercourse without a condom with a partner who had a penile piercing. In July 2014, he also reported receptive anal intercourse with multiple male partners in a group setting. The patient denied injection drug use, tattooing, or body piercings. His alanine aminotransferase (ALT) level increased from normal at baseline to 50 U/L in July 2014 and 549 U/L in September 2014. He reported an increase in fatigue over the preceding 2 months, as well as migratory arthralgias in his bilateral ankles and knees and a dull left flank pain for several weeks. In September 2014, HCV antibody was positive and HCV RNA was detected at 6938 IU/mL. Further testing confirmed the presence of HCV genotype 4 with repeat HCV RNA that remained detectable. The patient is currently being monitored for possible spontaneous viral clearance. Patient 2 was a 37-year-old MSM who initiated PrEP in October 2013. Between October 2013 and November 2014, he was diagnosed with rectal chlamydia on 3 occasions, rectal gonorrhea on 2 occasions, and syphilis once. He denied injection drug use, tattooing, or body piercings. In March 2014, his ALT was newly elevated at 743 U/L, and he reported a 2-month history of nausea, weight loss, arthralgias, and fatigue. HCV antibody was positive, and HCV RNA was detected at 34.5 million IU/mL. Further testing confirmed the presence of HCV genotype 1 with a repeat HCV RNA of 2.8 million IU/mL. He was treated with 12 weeks of pegylated interferon monotherapy, resulting in a sustained virologic response. In both cases, no risk factors for HCV infection were reported other than sexual intercourse without condom use. These incident HCV infections suggest an important role for ongoing HCV monitoring for HIV-uninfected MSM receiving PrEP given the potential for sexual transmission in this population. Patients initiating PrEP should be counseled regarding the risk of sexually transmitted HCV.
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Background: For over a decade we have known of an epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), but there still remains significant controversy over which bodily fluid(s) are responsible for HCV transmission in these men. Methods: We enrolled HIV-infected MSM with recent and chronic HCV infection and quantified HCV from rectal fluid obtained by blind swab. We compared the rectal HCV viral load (VL) with paired blood HCV VL. Results: We found rectal HCV shedding in 20 (47%) of 43 men, only one (2%) of whom had visible bleeding. Detection of rectal HCV shedding was associated with blood VL > 5 log10 IU/mL (p = .01), and 85% with blood VL > 5 log10 IU/mL had rectal shedding. The HCV VL of the rectal fluid ranged from 2.6 to 5.5 log10 IU/mL. Based on the median rectal fluid VL, the surface of an average human penis would be exposed to at least 2,300 IU of HCV for the duration of anal intercourse. Conclusion: This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM.
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Objectives: The Q80K polymorphism is a naturally occurring resistance-associated variant (RAV) in the hepatitis C virus (HCV) NS3 region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. Design and methods: Stored blood samples from HCV genotype 1a infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny. The most recent common ancestor (MRCA) was estimated with a coalescent-based model within a Bayesian statistical framework. Results: Study participants (n?=?150) were either men who have sex with men (MSM, 39%), people who inject drugs (17%), or patients with other (15%) or unknown/unreported (29%) risk behavior. Overall 45% was coinfected with HIV. Q80K was present in 36% (95% CI 28-44%) of patients throughout the sample collection period (2000-2015) and was most prevalent in MSM (52%, 95% CI 38-65%). Five MSM-specific transmission clusters were identified, of which 3 exclusively contained sequences with Q80K. The HCV-1a MRCA in the Netherlands was estimated in 1914 (95% higher posterior density (HPD) 1879-1944) and Q80K originated in 1957 (95% HPD 1942-1970) within HCV-1a clade I. All Q80K lineages could be traced back to this single origin. Conclusions: Q80K is a highly stable and transmissible RAV and was present in a large part of Dutch HIV-coinfected MSM. The introduction and expansion of Q80K variants in this key population suggest a founder effect, potentially jeopardizing future treatment with simeprevir.
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Conclusion: Treatment interventions to curb the HCV epidemic among HIV-infected MSM are effective if high-risk behavior does not increase as it has during the last decade. Reducing high-risk behavior associated with HCV transmission would be the most effective intervention for controlling the HCV epidemic, even if this was not accompanied by an increase in treatment uptake or efficacy. This article is protected by copyright. All rights reserved.
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Importance Several randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM).Objective To assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States.Design, Setting, and Participants Demonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015.Interventions A combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring.Main Outcomes and Measures Concentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition.Results Overall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P < .001) were less likely to have protective levels, whereas those with stable housing (86.8%; P = .02) and those reporting at least 2 condomless anal sex partners in the past 3 months (88.6%; P = .01) were more likely to have protective levels. The mean number of anal sex partners declined during follow-up from 10.9 to 9.3, whereas the proportion engaging in condomless receptive anal sex remained stable at 65.5% to 65.6%. Overall STI incidence was high (90 per 100 person-years) but did not increase over time. Two individuals became HIV infected during follow-up (HIV incidence, 0.43 [95% CI, 0.05-1.54] infections per 100 person-years); both had tenofovir diphosphate levels consistent with fewer than 2 doses/wk at seroconversion.Conclusions and Relevance The incidence of HIV acquisition was extremely low despite a high incidence of STIs in a large US PrEP demonstration project. Adherence was higher among those participants who reported more risk behaviors. Interventions that address racial and geographic disparities and housing instability may increase the impact of PrEP.
Article
Objective: High rates of hepatitis C virus (HCV) reinfections among HIV-infected MSM following clearance of a primary infection suggest absence of protective immunity. Here, we investigated the incidence of HCV super and reinfections in 85 HIV-infected MSM with incident HCV infection. Design and methods: Serial sequencing of a fragment of NS5B and the HCV envelope was used to longitudinally characterize the virus. If the primary genotype was still present at the most recent viremic time point, as indicated by the NS5B sequence analysis, serial E2/HVR1 sequence analysis was performed to distinguish a new infection with the same genotype (clade switch) from intrahost evolution. Incidence rate and cumulative incidence of secondary infections were estimated, and the effect of the primary genotype (1a versus non1) on the risk of acquiring a second infection with the same genotype was determined using Cox proportional-hazards analysis. Results: Among 85 patients with a median follow-up of 4.8 years, incidence rate of secondary infections was 5.39 cases/100 person-years (95% confidence interval 3.34-8.26). Cumulative incidence of genotype switches was markedly higher than the cumulative incidence of clade switches (26.7 versus 4.8% at 5 years, respectively). In patients with HCV-1a as primary infection, the risk for acquiring another HCV-1a infection was reduced compared to those with a primary non-HCV-1a subsequently acquiring HCV-1a (hazard ratio 0.25, 95% confidence interval 0.07-0.93). Conclusion: Risk of acquiring a secondary infection with the primary genotype was strikingly reduced compared with the risk of acquiring a secondary infection with a different genotype.
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The burden of hepatitis C virus (HCV) is high among people who inject drugs (PWID) and prisoners, and increasing among HIV-infected MSM, who are key populations for HCV transmission in high-income countries and may also play a role in many in low- and middle-income countries. There is an increasing interest in the use of HCV antiviral treatment for prevention in these populations. Numerous theoretical modelling studies have explored the potential impact of HCV treatment for prevention among PWID in a range of global settings, generally finding that modest and achievable levels of HCV treatment, especially with interferon-free direct-acting antiviral therapy (IFN-free DAAs), could substantially reduce HCV chronic prevalence among PWID within the next 10-20 years. In addition, modelling studies have shown HCV testing and treatment in prison (including prevention benefits) could be cost-effective if continuity of care is ensured, or HCV treatments are shortened with DAAs. Modelling work among HIV-infected MSM has shown that further HCV treatment scale-up is likely required despite high treatment rates in this population. However, no empirical studies have explored whether HCV treatment can reduce HCV prevalence and prevent onwards transmission among those at risk of transmission. HCV treatment for key populations such as PWID, prisoners and MSM could become an important HCV prevention intervention, especially in the IFN-free DAA era. However, there is an urgent need to test these hypotheses through empirical studies.