DC-SIGN Polymorphisms Associate with Risk of Hepatitis C Virus Infection Among Men who Have Sex with Men but not Among Injecting Drug Users.
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ABSTRACT:
SUBMITTER: Steba GS
PROVIDER: S-EPMC5853896 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
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DC-SIGN Polymorphisms Associate with Risk of Hepatitis C Virus Infection Among Men who Have Sex with Men but not Among Injecting Drug Users.
Steba Gaby S GS Koekkoek Sylvie M SM Vanhommerig Joost W JW Brinkman Kees K Kwa David D Van Der Meer Jan T M JTM Prins Maria M Berkhout Ben B Tanck Michael M Paxton William A WA Molenkamp Richard R Schinkel Janke J
The Journal of infectious diseases 20180101 3
We aimed to identify whether genetic polymorphisms within L-SIGN or DC-SIGN correlate with hepatitis C virus (HCV) susceptibility. A men who have sex with men (MSM) and an injecting drug users (IDU) cohort of HCV cases and multiple-exposed uninfected controls were genotyped for numerous L-SIGN and DC-SIGN polymorphisms. DC-SIGN single nucleotide polymorphisms (SNPs) -139, -871, and -939 correlated with HCV acquisition in the MSM cohort only. When the same SNPs were introduced into a transcriptio ...[more]
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Project description:BackgroundThere is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium.MethodsThis observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test.ResultsEighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3-56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4-2.0).ConclusionReinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe. Trial registration clinicaltrials.gov NCT04251572, Registered 5 Feb 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04251572 .
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Project description:Patients with acute hepatitis C virus (HCV) infection who receive treatment achieve high rates of sustained virologic response (SVR), but few studies have examined outcomes among injecting drug users (IDUs). We evaluated the efficacy of treatment of recent HCV infection in IDUs with acute and early chronic HCV.We analyzed data from the Australian Trial in Acute Hepatitis C-a prospective study of the natural history and treatment outcomes of patients with recent HCV infection. Participants eligible for the study had their first anti-HCV antibody-positive test result within the past 6 months and either acute clinical HCV within the past 12 months or documented anti-HCV seroconversion within 24 months. Participants with HCV received pegylated interferon-alfa-2a (180 microg/wk, n = 74); those with HCV/human immunodeficiency virus (HIV) co-infection received pegylated interferon-alfa-2a (180 microg/wk) with ribavirin (n = 35) for 24 weeks.From June 2004 to February 2008, 167 participants were enrolled in the Australian Trial in Acute Hepatitis C; 79% had injected drugs in the previous 6 months. Among 74 with only HCV, the SVRs were 55% and 72% by intention-to-treat and per-protocol analysis, respectively. In multivariate analyses, baseline factors independently associated with lower SVR included decreased social functioning and current opiate pharmacotherapy. Adherent participants had higher SVR rates (63% vs 29%; P = .025). Of the 35 participants with HCV/HIV co-infection, the SVRs were 74% and 75% by intention-to-treat and per-protocol analysis, respectively.Treatment of recent HCV infection among IDUs, including those with HIV co-infection, is effective. Strategies to engage socially marginalized individuals and increase adherence should improve treatment outcomes in this population.
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Project description:BACKGROUND:Hepatitis B virus (HBV) infection is a major health problem worldwide. OBJECTIVES:The aim of this study was to investigate the frequency of occult hepatitis B infection (OBI) and its associated risk factors, together with the molecular characterization of the virus in injecting drug users of Tehran. PATIENTS AND METHODS:The study consisted of 229 injecting drug users. Serum samples were collected and tested for the presence of hepatitis B core antibody (HBcAb) and hepatitis B surface antigen (HBsAg) by an enzyme-linked immunosorbent assay (ELISA). HBV B virus DNA was extracted from the serum samples, and a fragment of the S gene was amplified using the nested polymerase chain reaction. The genotype, subgenotypes, subtype, and S gene mutation of HBV were determined by direct sequencing. A phylogenetic tree was constructed using the neighbor-joining method. RESULTS:Sixty-four (28%) participants were HBcAb positive, 59 cases were HBcAb positive and HBsAg negative, and 5 cases were HBsAg positive. Hepatitis B DNA was found in three HBsAg-positive cases. Thirteen of 59 (22%) individuals were hepatitis B DNA positive. The phylogenetic tree of hepatitis B DNA showed the existence of genotype D. The only significant correlation was between sharing a syringe and OBI. CONCLUSIONS:In comparison with the rate of HBcAb positivity reported in other Iranian studies, the rate was higher in the present study. There were a few variations, genotypes, and subtypes among the infected injecting drug users. Further investigations are needed to unravel the molecular characterization of OBI.
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Project description:Adherence to HCV therapy impacts sustained virological response (SVR) but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (?80% of PEG-IFN doses, ?80% treatment), on-treatment adherence, and treatment completion in a study of treatment of recent HCV infection (ATAHC).Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180?g/week, n=74) and those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35), for a planned 24 weeks. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence.A total of 109 out of 163 patients received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed ?1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23, and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76) of cases, respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29, p=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those patients with ?80/80 PEG-IFN adherence (67% vs. 35%, p=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%, p=0.309). SVR in those patients discontinuing therapy between 0-4, 5-19, 20-23, and 24 weeks was 9%, 33%, 43%, and 76%, respectively (p<0.001).High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy.
| S-EPMC3117933 | biostudies-literature
Project description:BackgroundWe estimate the prevalence of drug injection, the variables associated with having ever injected and the proportion of ever injectors whose first drug injection was for having sex; we describe the first drug injection episode, analyze the drugs most frequently injected and estimate the prevalence of risky injecting behaviors.MethodsThe participants were 3387 MSM without a previous HIV diagnosis attending four HIV/STI diagnosis services in Madrid and Barcelona. Lifetime prevalence and prevalence ratios (PRs) by different factors were calculated using Poisson regression models with robust variance. We compared the characteristics of first drug injection episode, lifetime injection and risky injecting behaviors of those whose first injection was for sex (FIS) with those whose was not (non-FIS).ResultsLifetime prevalence of injection was 2.1% (CI 1.7-2.7). In the multivariate analysis, it was strongly associated with having been penetrated by more than five men in the last 12 months (aPR = 10.4; CI 2.5-43.4) and having met most of their partners at private parties (aPR = 7.5; CI 4.5-12.3), and less strongly with other factors. Of those who had ever injected drugs, 81.9% injected for sex the first time they injected drugs (FIS). At first injection, FIS participants had a mean age of 31 years, 62.7% used mephedrone and 32.2% methamphetamine on that occasion. Of this FIS group 39.0% had ever shared drugs or equipment and 82.6% had always shared for sex. Some 30.8% of non-FIS reported having also injected drugs for sex later on.ConclusionsOnly two out of a hundred had ever injected, most to have sex and with frequent drug or injecting equipment sharing. Injecting for sex is the most common first episode of drug injection and is the most efficient risky behavior for the transmission of HIV, hepatitis B or C and other blood-borne infections. MSM participating in private parties should be considered a priority group for prevention policies.
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Project description:Injection drug use is increasingly an important route of HIV transmission in Romania (from 1.5% of the newly diagnosed cases prior to 2010 to 31% in 2013). In this study we investigated the viral characteristics and relationships in newly HIV infected persons who inject drugs in Bucharest, Romania. Results:HIV-1 pol sequencing, followed by phylogenetic and clustering analysis was performed on blood from 37 injecting drug users (IDUs) newly diagnosed with HIV infection. While HIV subtype F1, the dominant strain in Romania since 1990, remains prevalent, new subtypes were found including G, B, B/G and B/F recombinants. Overall, 27 of the available sequences (72.9%) clustered with at least one other. Network and phylogenetic analysis revealed tight monophyletic clusters for both subtypes F and G, with short genetic distances between sequences, suggesting recent numerous acute to acute transmissions or single burst-type episodes. No transmitted drug-resistance mutations were identified. Greater immunosuppression was present in subjects forming the subtype G cluster, possibly indicating a faster rate of progression associated with this subtype. Conclusions:The recent increasing numbers of IDU related HIV transmissions in Bucharest, has resulted in closely-knit transmission networks that maychange the genetic profile of the local HIV epidemic.
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Project description:ObjectiveThe aim of this study was to develop a framework and best estimates of prevalence for the most at risk populations (MARPs) for HIV/AIDS to include sex workers (SW), men who have sex with men (MSM) and injecting drug users (IDUs) in order to evaluate national HIV/AIDS programmatic targets across the Republic of Serbia.DesignA national, cross-sectional study and direct enumeration, multiplier and benchmark methods with integrated bio-behavioural surveys, capture/recapture and methods with Wald and Clopper-Pearson CIs were used.SettingThis study was carried out in the three largest cities and main regions of Serbia, the capital city, Belgrade, (population 1 639 121 persons), the Vojvodina region with main city Novi Sad (population 335 701) and the rest of Serbia with main city Nis (population 257 867).ParticipantsA total of 1301 respondents from the defined MARPs completed the survey in the 2009/2010 period across the three cities.Primary outcome measuresEstimates of the hidden numbers at risk of HIV/AIDS.ResultsIt was estimated that there were 1775-6027 SW between 18 and 49 years in Serbia in 2009. For MSM, national estimates for 2009 ranged from 20 789 to 90 104 individuals aged between 20 and 49 years. For IDU, a possible range of 12 682-48 083 individuals aged between 15 and 59 years in 2009 was estimated.ConclusionsFor service planning across Central and Eastern Europe, it is important to highlight how credible estimates can be achieved and compared with numbers within HIV/AIDS-prevention programmes. Within needle exchange programmes, only 5.4-20.5% of the estimated population was observed and this proportion was lower within methadone treatment data. Results have implications for future IDU treatment and HIV incidence and spread across all populations at risk.
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Project description:The aim of this study was to characterize the current molecular epidemiology of hepatitis C virus (HCV) infection and evaluate the evolutionary patterns of HCV subtypes in Beijing, China, among different subpopulations.The whole blood samples and behavioral data were collected from a total of 10,354 subjects, including drug users (DUs), men who have sex with men (MSM), and the general population, in Beijing from 2010 to 2011. Samples were tested for HCV infection using both enzyme-linked immunosorbent assay (ELISA) and real-time PCR. All viremic subjects were then sequenced by nested PCR over core/E1 and NS5B regions. Phylogenetic and phylogeographic analysis was performed by BEAST software.In total, 217 subjects (2.1%) were tested positive for HCV by antibody or vRNA-based testing. HCV prevalence rates for DUs, MSM, and the general population were 26.2%, 0.54%, and 0.37%, respectively. The 156 HCV RNA-positive samples were sequenced. Nine HCV genotypes, including 1a, 1b, 2a, 3a, 3b, 6a, 6n, 6u and 6v, were detected. The most prevalent subtypes were 3b (36.09%), 1b (32.54%), and 3a (16.57%). Bayesian evolutionary analysis estimated that the time of introduction of subtype 1b into Beijing was 2004 (95% CI: 1997.7, 2007.7), with subtypes 3a and 3b being introduced later in 2006. Evolutionary analyses further suggested that subtype 1b from Beijing and Shanghai were closely related, whereas subtype 3a sequences were more similar with sequences from Yunnan, Guangzhou, Hong Kong, and Jiangsu. Subtype 3b sequences were closely related to those from Yunnan, Guangdong, and Hong Kong.Thus, the current HCV epidemic in Beijing is complex, heavily affecting DUs, and involving multiple genotypes that likely spread from different regions in China with its large migrant population.
| S-EPMC4753893 | biostudies-literature
Project description:In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred until the final years of the decade, and is the least cost-effective of the scenarios.
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Project description:The critical events in clearance or persistence of hepatitis C virus (HCV) infection are unknown but likely to be determined early in acute infection. Type 1 and type 2 cytokine production was assessed by HCV peptide ELISpot and multiplex in vitro cytokine production assays in longitudinally collected samples from 20 untreated participants enrolled in the Australian Trial in Acute Hepatitis C (ATAHC); a prospective cohort of acute HCV infection (77% injecting drug users, IDU). Significantly higher interleukin-10 (IL-10) production (P = 0.048), in the relative absence of interferon-gamma (IFN-γ) and IL-2 production, was present early in HCV infection in those who progressed to chronic infection. In contrast, viral clearance was associated with a greater magnitude and broader specificity of IFN-γ (magnitude P < 0.001, breadth P = 0.004) and IL-2 responses, in the relative absence of IL-10. Early IL-10 production was correlated with higher HCV RNA level at baseline (P = 0.046) and week 12 (P = 0.018), while IFN-γ and IL-2 production was inversely correlated with HCV RNA level at baseline (IFN-γ P = 0.020, IL-2 P = 0.050) and week 48 (IFN-γ P = 0.045, IL-2 P = 0.026). Intracellular staining (ICS) indicated the HCV-specific IFN-γ response was primarily from CD8(+) T cells and NK cells, whereas IL-10 production was predominantly from monocytes, with a subset of IL-10 producing CD8(+) T cells present only in those who progressed to chronic infection. IL-10, an immunoregulatory cytokine, appears to play a key role in progression to chronic HCV infection.
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