Hepatitis C virus vaccines among people who inject drugs.
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ABSTRACT:
SUBMITTER: Cox AL
PROVIDER: S-EPMC3722079 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
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Hepatitis C virus vaccines among people who inject drugs.
Cox Andrea L AL Thomas David L DL
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130801
Most people who inject drugs (PWID) are infected with hepatitis C virus (HCV), and PWID have the highest risk of HCV infection of any risk group. The incidence of HCV infection is 5%-25% per year, demonstrating continued need for HCV infection prevention in PWID. Existing data in chimpanzees and PWID suggest that protective immunity against persistent HCV infection is achievable. Due to the high incidence of infection, PWID are both the most likely to benefit from a vaccine and a population in w ...[more]
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Project description:BackgroundApproximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok.MethodsThe Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes.ResultsThe median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%).ConclusionThe prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.
| S-EPMC7954142 | biostudies-literature
Project description:Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve existing surveillance data and help guide treatment. While intra-host viral diversity quantifications such as Shannon entropy have previously been utilized for estimating duration of infection, these studies characterize the viral population from only a relatively short segment of the HCV genome. In this study intra-host diversities were examined across the HCV genome in order to identify the region most reflective of time and the degree to which these estimates are influenced by high-risk activities including those associated with HCV acquisition. Shannon diversities were calculated for all regions of HCV from 78 longitudinally sampled individuals with known seroconversion timeframes. While the region of the HCV genome most accurately reflecting time resided within the NS3 gene, the gene region with the highest capacity to differentiate acute from chronic infections was identified within the NS5b region. Multivariate models predicting duration of infection from viral diversity significantly improved upon incorporation of variables associated with recent public, unsupervised drug use. These results could assist the development of strategic population treatment guidelines for high-risk individuals infected with HCV and offer insights into variables associated with a likelihood of transmission.
| S-EPMC8113533 | biostudies-literature
Project description:ObjectivesFor both HIV-1 and hepatitis C virus (HCV), assessing the stringency of the transmission process is a scientific priority. Enumerations of transmitted/founder (TF) viruses have shown a strict transmission bottleneck in sexual transmission of HIV-1 and a wide range in the multiplicity of infection in HCV. Here, we aim to determine the stringency of parenteral transmission for HIV-1 and HCV in people who inject drugs (PWID).DesignWe used molecular sequencing and several complementary analyses to enumerate the TF HIV-1 and HCV variants in a well described cohort of PWID in Xinjiang, China.MethodsWe performed single genome sequencing of HIV-1 env and 5' half HCV genomes, then applied phylogenetic analysis and validated models of early virus diversification to enumerate TF viruses in 60 PWID. We used multivariate analysis to determine correlates of multivariant transmission (MVT).ResultsWe generated 1070 env region sequences from 33 HIV-1 early infected individuals and 773 5' half region sequences from 27 HCV early infected individuals. We found rates of MVT of 39 and 54%, respectively, for HIV-1 and HCV, with a limited range in the number of TF viruses in both infections. Behavioural characteristics suggested high-risk injection practices and lower risk sexual practices; we did not find an association between any specific behaviours and MVT.ConclusionMVT is frequent in parenteral transmission of both HIV-1 and HCV in Xinjiang PWID, indicating a less stringent transmission process than sexual transmission.
| S-EPMC5765877 | biostudies-literature
Project description:UnlabelledLittle is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age≥40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36).ConclusionIn this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations.
| S-EPMC4211947 | biostudies-literature
Project description:While people who inject drugs are at high risk of hepatitis C virus (HCV) infection and will be the target population for future HCV vaccine trials, little is known about clinical trial literacy (CTL) in this group. We assessed the impact of a brief intervention (BI) designed to improve HCV vaccine CTL among people who inject drugs in Sydney, Australia.People who inject drugs enrolled in a community-based prospective observational study between November 2008 and September 2010 (n?=?102) completed a CTL assessment followed immediately by the BI. Post-test assessment was conducted at 24 weeks.The median age of the sample was 27 years, 73% were male and 60% had 10 or less years of schooling. The median time since first injection was 5 years and 20% reported daily or more frequent injecting. The mean number of correct responses increased from 5.3 to 6.3/10 (t?=?-4.2; 101df, P?<?0.001) 24 weeks post-intervention. Statistically significant differences were observed for three knowledge items with higher proportions of participants correctly answering questions related to randomisation (P?=?0.002), blinding (P?=?0.005) and vaccine-induced seropositivity (P?=?0.003) post-intervention.A significant increase in HCV vaccine CTL was observed, suggesting that new and relatively novel concepts can be learned and recalled in this group. These findings support the feasibility of future trials among this population. [Correction added on 21 November 2012, after first online publication: T-score for mean number of correct responses was corrected to '-4.2' in the Results section.]
| S-EPMC3567229 | biostudies-other
Project description:BACKGROUND: The risk-related behaviours and practices associated with injection drug use remain a driver of HIV and hepatitis C virus (HCV) transmission throughout the world. Here we evaluated HIV and HCV transmission patterns in the context of social networks of injection drug users (IDU) recruited from a higher incidence region in order to better understand factors that contribute to ongoing transmission among IDU. METHODS: IDU recruited through a chain-referral method provided biological specimens for analysis. HIV and HCV positive specimens were sequenced and analyzed using phylogenetic methods (Neighbour-joining and bayesian) and transmission patterns of HIV and HCV evaluated in the context of the recruitment networks. RESULTS: Among the 407 recruited IDU, HCV and HIV prevalence were 60.6% and 10.1%, respectively; 98% of HIV positive individuals were co-infected with HCV. Thirty-six percent of HCV sequences were associated with clusters, compared to 67% of HIV sequences. Four (16.7%) of the 24 HCV clusters contained membership separated by 2 or fewer recruitment cycles, compared to 10 (41.6%) derived from more than one recruitment component. Two (28.6%) of the 7 HIV clusters contained membership separated by 2 or fewer recruitment cycles while 6 (85.7%) were composed of inter component membership. CONCLUSIONS: Few HIV and HCV transmissions coincided with the recruitment networks, suggesting that they occurred in a different social context or a context not captured by the recruitment network. However, among the complete cohort, a higher degree of HIV clustering indicates many are recent infections originating from within current social networks, whereas a larger proportion of HCV infections may have occurred earlier in injecting history and in the context of a different social environment.
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Project description:People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10-58.38; p = 0.005). Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.
| S-EPMC8432451 | biostudies-literature
Project description:The availability of generic direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has prompted many low-and-middle-income countries to launch HCV elimination programs. Because the efficacy of some of these generic DAAs varies by HCV viral subtype, information on subtype distribution can contribute important information to these elimination programs. We conducted a cross-sectional serosurvey to characterize HCV subtype diversity among HIV positive people who inject drugs (PWID) across 14 cities in India. Of 801 HIV positive PWID sampled, 639 tested HCV antibody positive (78.9%). Among 105 samples sequenced, genotype 3 (58.1%) was the most commonly observed followed by genotype 1 (36.2%) and genotype 6 (5.7%). Of the genotype 3 infections, 65% were subtype 3a and 35% were subtype 3b. Of the genotype 1 infections, 94% were subtype 1a and 6% were subtype 1b. All genotype 6 samples were subtype 6n. There was some variability in genotype diversity depending on geographic region and PWID epidemic stage with greater diversity observed in older PWID epidemics. One sequence, HY018, did not cluster with any known reference sequences in phylogenetic analysis. Nearly 80% of HIV infected PWID across India are co-infected with HCV, and subtype prevalence and genetic diversity varied by region and PWID epidemic stage. HCV elimination programs in India will need to consider HCV subtype.
| S-EPMC6917681 | biostudies-literature
Project description:BackgroundPeople who inject drugs (PWID) continue to experience the highest burden of hepatitis C virus (HCV). We aimed to characterize HCV antibody prevalence, determinants of infection, and the cascade of engagement in HCV care among PWID in Iran.MethodsParticipants were recruited in 11 cities of Iran using respondent-driven sampling. PWID underwent a structured interview capturing measures on socio-demographics, behaviors, and the HCV cascade of care. HCV and HIV were tested using antibody rapid tests. Multivariable logistic regression models identified characteristics associated with HCV seropositivity.ResultsHCV antibody prevalence was 26.0% among 2684 PWID enrolled. Of 699 participants who were HCV antibody positive, 88 (12.6%) were aware of past infections. HCV antibody prevalence was associated with older age (adjusted odds ratio [aOR] 2.09; 95% CI 1.18, 3.71), lower education (aOR 1.31; 95% CI 1.02, 1.69), >10 years of injecting (aOR 6.03; 95% CI 4.10, 8.85), methamphetamine injection (aOR 1.46; 95% CI 1.07, 1.99), daily injection drug use (aOR 1.26; 95% CI 1.01, 1.58), needle/syringe sharing (aOR 2.04; 95% CI 1.24, 3.34), recent incarceration (aOR 1.74; 95% CI 1.30, 2.32), and HIV seropositivity (aOR 7.93; 95% CI 4.12, 15.24). Additionally, 12.0% had ever tested for HCV, 4.0% had previously tested reactive for HCV antibody, and 3.7% had received an HCV diagnosis. Of diagnosed cases, 44.4% were linked to care, 15.2% initiated treatment, and 3.0% achieved sustained virologic response.ConclusionOur data show a high prevalence of HCV antibody and low engagement in HCV care, underscoring an unmet need for HCV prevention, screening, and treatment among PWID in Iran. HCV prevention and treatment programs tailored for PWID are needed to enhance harm reduction efforts and access to HCV care in Iran.
| S-EPMC10440186 | biostudies-literature
Project description:Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.
| S-EPMC8584601 | biostudies-literature