Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs.
Ontology highlight
ABSTRACT:
SUBMITTER: Durand M
PROVIDER: S-EPMC8584601 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.
| S-EPMC3815209 | biostudies-literature
Project description: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 which vaccine efficacy could be tested. Challenges to testing a vaccine in PWID are significant. However, the first HCV vaccine trial in at-risk HCV-uninfected PWID was initiated in 2012. The results will likely guide future vaccine development and strategies for vaccination of this and other high-risk populations.
| S-EPMC3722079 | biostudies-literature
Project description:This study aims to understand the time-to-treatment initiation pre and post DAA access to inform strategies to improve HCV care. The data for our study were derived from the SuperMIX cohort study of people who inject drugs in Melbourne, Australia. Time-to-event analysis using Weibull accelerated failure time was performed for data collected between 2009 and 2021, among a cohort of HCV-positive participants. Among 223 participants who tested positive for active hepatitis C infection, 102 people (45.7%) reported treatment initiation, with a median time-to-treatment of 7 years. However, the median time-to-treatment reduced to 2.3 years for those tested positive after 2016. The study found that treatment with Opioid Agonist Therapy (TR 0.7, 95% CI 0.6-0.9), engagement with health or social services (TR 0.7, 95% CI 0.6-0.9), and having a first positive HCV RNA test after March 2016 (TR 0.3, 95% CI 0.2-0.3) were associated with a reduced time-to-treatment initiation. The study highlights the need for strategies to improve engagement with health services, including drug treatment services into routine HCV care to achieve timely treatment.
| S-EPMC10226186 | biostudies-literature
Project description:BackgroundPeople who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use-related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown.MethodsIn this prospective, open-label, observational trial at a harm reduction organization's drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR.ResultsEighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04).ConclusionsThe Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use.Clinical trials registrationNCT03221309.
| S-EPMC7755091 | biostudies-literature
Project description: Not available
| S-EPMC9276623 | biostudies-literature
Project description:BackgroundComprehensive information on the incidence and duration of hepatitis C virus (HCV) infection for people who inject drugs (PWID) in Ireland is not available. We created an incidence curve of injecting drug use in Ireland and subsequently estimated incidence of hepatitis C virus (HCV) infection.MethodsAnonymised data from the National Drug Treatment Reporting System (NDTRS) were used to identify all people who inject drugs (PWIDs) and who entered drug treatment for the first time between 1991 and 2014. A curve, estimating the incidence of injecting, was created to plot PWIDs by year of commencing injecting. The curve was adjusted for missing data on PWIDs in treatment and for PWIDs who were never treated. An adjustment was made to account for injectors who had never shared injecting equipment. The incidence of HCV infection and chronic infection in PWIDs was estimated by applying published rates.ResultsBetween 1991 and 2014, 14,320 injectors were registered on NDTRS. The majority were young (median age 25 years), male (74%), lived in Dublin (73%) and injected an opiate (e.g. heroin) (94%). The estimated total number of injectors up to the end of 2014 was 16,382. An estimated 12,423 (95% CI 10,799-13,161) were infected with HCV, and 9,317 (95% CI 8,022-9,996) became chronically infected. The estimated annual number of new HCV infections among PWIDs increased steeply from the late 1970s and peaked in 1998. By 2014, almost 30% of injectors were estimated to have been infected for over 20 years.ConclusionsThis is the first comprehensive national estimate of the incidence of HCV in PWIDs in Ireland and will inform planning and developing appropriate health care services.
| S-EPMC6171004 | biostudies-literature
Project description:BackgroundTelemedicine offers the opportunity to provide clinical services remotely, thereby bridging geographic distances for people engaged in the medical system. Following the COVID-19 pandemic, the widespread adoption of telemedicine in clinical practices has persisted, highlighting its continued relevance for post-pandemic healthcare. Little is known about telemedicine use among people from socially marginalized groups.MethodsThe No One Waits (NOW) Study is a single-arm clinical trial measuring the acceptability, feasibility, and safety of an urban point-of-diagnosis hepatitis C (HCV) treatment initiation model delivered in a non-clinical community setting. Participants enrolled in the NOW Study are recruited via street outreach targeting people experiencing homelessness and injecting drugs. Throughout the NOW Study, clinical care is delivered through a novel staff-facilitated telemedicine model that not only addresses geographic and transportation barriers, but also technology and medical mistrust, barriers often unique to this population. While clinicians provide high-quality specialty practice-based care via telemedicine, on-site staff provide technical support, aid in communication and rapport, and review the clinicians' instructions and next steps with participants following the visits. Research questionnaires collect information on participants' experience with and perceptions of telemedicine (a) prior to treatment initiation and (b) at treatment completion.DiscussionFor people from socially marginalized groups with HCV infection, creative person-centered care approaches are necessary to diagnose, treat, and cure HCV. Although non-clinical, community-based staff-facilitated telemedicine requires additional resources compared to standard-of-care telemedicine, it could expand the reach and offer a valuable entrance into technology-delivered care for socially marginalized groups.Trial registrationNCT03987503.
| S-EPMC11012066 | biostudies-literature
Project description:BackgroundMany people who inject drugs in the United States have chronic hepatitis C virus (HCV). On-site treatment in opiate agonist treatment (OAT) programs addresses HCV treatment barriers, but few evidence-based models exist.MethodsWe evaluated the cost-effectiveness of HCV treatment models for OAT patients using data from a randomized trial conducted in Bronx, New York. We used a decision analytic model to compare self-administered individual treatment (SIT), group treatment (GT), directly observed therapy (DOT), and no intervention for a simulated cohort with the same demographic characteristics of trial participants. We projected long-term outcomes using an established model of HCV disease progression and treatment (hepatitis C cost-effectiveness model: HEP-CE). Incremental cost-effectiveness ratios (ICERs) are reported in 2016 US$/quality-adjusted life years (QALY), discounted 3% annually, from the healthcare sector and societal perspectives.ResultsFor those assigned to SIT, we projected 89% would ever achieve a sustained viral response (SVR), with 7.21 QALYs and a $245 500 lifetime cost, compared to 22% achieving SVR, with 5.49 QALYs and a $161 300 lifetime cost, with no intervention. GT was more efficient than SIT, resulting in 0.33 additional QALYs and a $14 100 lower lifetime cost per person, with an ICER of $34 300/QALY, compared to no intervention. DOT was slightly more effective and costly than GT, with an ICER > $100 000/QALY, compared to GT. In probabilistic sensitivity analyses, GT and DOT were preferred in 91% of simulations at a threshold of <$100 000/QALY; conclusions were similar from the societal perspective.ConclusionsAll models were associated with high rates of achieving SVR, compared to standard care. GT and DOT treatment models should be considered as cost-effective alternatives to SIT.
| S-EPMC7318779 | biostudies-literature
Project description:ImportanceThe success of direct-acting antiviral therapies for chronic hepatitis C virus (HCV) infection led the World Health Organization to set elimination targets by 2030. For the United States to achieve these benchmarks, public health responses must target high-risk populations, such as people who inject drugs (PWID), a group with high rates of HCV incidence and low rates of treatment uptake.ObjectiveTo evaluate potential improvements in the HCV care cascade among PWID, focusing on improved testing, treatment uptake, and access to harm reduction.Design, setting, and participantsThis decision analytic model used a differential equation-based dynamic transmission model based on data from New Hampshire, an illustrative state with a large number of PWID and limited HCV treatment infrastructure. Surveillance data through 2020 was used for model parameterization, and the final analysis was conducted in May 2021.Main outcomes and measuresModel forecasts of chronic HCV cases and advanced-stage HCV outcomes from 2022 to 2045.ResultsA total of 6 scenarios were tested: (1) the base case, (2) improved harm reduction, (3) improved testing, (4) improved treatment, (5) improved testing and treatment, and (6) improved testing, treatment, and harm reduction. All scenarios with improved testing, treatment uptake, and/or access to harm reduction were associated with decreases in forecasted HCV prevalence and HCV-associated mortality compared with the base case. Improving harm reduction, testing, and treatment individually were forecast to reduce prevalence of HCV in 2045 from 69.7% in the base case to 62.8%, 45.7%, and 35.5%, respectively. Combining treatment and testing improvements was associated with a 2045 prevalence of 0.3%; adding harm reduction improvements was associated with further reductions in prevalence forecasts (to 0.2%), with fewer total treatments (10 960 vs 13 219 from 2022-2045).Conclusions and relevanceIn this modeling study, no single intervention was projected to achieve World Health Organization HCV elimination targets. Scenarios with improvements in both testing and treatment were associated with a prevalence of less than 3% by 2030 and achieved elimination targets. Adding improvements in harm reduction was associated with faster reductions in prevalence and fewer treatments.
| S-EPMC8335578 | biostudies-literature
Project description:The HIV treatment cascade is an effective tool to track progress and gaps in the HIV response among key populations. People who inject drugs (PWID) remain the most affected key population in Ukraine with HIV prevalence of 22% in 2015. We performed secondary analysis of the 2017 Integrated Bio-Behavioral Surveillance (IBBS) survey data to construct the HIV treatment cascade for PWID and identify correlates of each indicator achievement. The biggest gap in the cascade was found in the first "90", HIV status awareness: only 58% [95% CI: 56%-61%] of HIV-positive PWID reported being aware of their HIV-positive status. Almost 70% [67%-72%] of all HIV-infected PWID who were aware of their status reported that they currently received antiretroviral therapy (ART). Almost three quarters (74% [71%-77%]) of all HIV-infected PWID on ART were virally suppressed. Access to harm reduction services in the past 12 months and lifetime receipt of opioid agonist treatment (OAT) had the strongest association with HIV status awareness. Additionally, OAT patients who were aware of HIV-positive status had 1.7 [1.2-2.3] times the odds of receiving ART. Being on ART for the last 6 months or longer increased odds to be virally suppressed; in contrast, missed recent doses of ART significantly decreased the odds of suppression. The HIV treatment cascade analysis for PWID in Ukraine revealed substantial gaps at each step and identified factors contributing to achievement of the outcomes. More intensive harm reduction outreach along with targeted case finding could help to fill the HIV awareness gap among PWID in Ukraine. Scale up of OAT and community-level linkage to care and ART adherence interventions are viable strategies to improve ART coverage and viral suppression among PWID.
| S-EPMC7775055 | biostudies-literature