Dataset Information

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

ABSTRACT: People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial DNA (mtDNA) genotoxicity. We have previously reported acute mtDNA toxicity of three DAA regimens among PWID with a strong impact on the rate of mtDNA deletion, less on the quantity of mtDNA copy per cell at sustained viral response at 12 weeks (SVR12). Herein, we report the mtDNA parameters nine months after drug discontinuation. We observed that the percentage of the deleted mtDNA genome increased over time. No exposure to any other genotoxicants during this period was associated with a high deletion percentage, suggesting that the replicative advantage of the deleted molecules outweighed their elimination processes. Such observation calls for longer-term follow-up and may contribute to the molecular basis of subclinical side effects of DAA treatments.

SUBMITTER: Durand M

PROVIDER: S-EPMC9599189 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

Durand Mélusine M Nagot Nicolas N Nhu Quynh Bach Thi QBT Vizeneux Amélie A Thuy Linh Le Thi LLT Duong Huong Thi HT Thanh Binh Nguyen BN Rapoud Delphine D Vallo Roselyne R Quillet Catherine C Tran Hong Thi HT Michel Laurent L Tuyet Thanh Nham Thi TNT Hai Oanh Khuat Thi OKT Hai Vinh Vu VV Feelemyer Jonathan J Vande Perre Philippe P Des Jarlais Don D Minh Khue Pham KP Laureillard Didier D Molès Jean-Pierre JP

Biomedicines 20221012 10

People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial ...[more]

PMID: 36289803

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Project description:BACKGROUND:Elimination of hepatitis C virus (HCV) among people who inject drugs (PWID) is a costly investment, so strategies should not only focus on eliminating the disease, but also on preventing disease resurgence. The aims of this study are to compute the minimum necessary antiviral therapies to achieve elimination with and without the additional expansion of harm reduction (HR) programs and to examine the sustainability of HCV elimination after 2030 if treatment is discontinued. METHOD:We considered two types of epidemic (with low (30%) and high (50%) proportion of PWID who engage in sharing equipment (sharers)) within three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming a baseline HR coverage of 40%. We define sustainable elimination strategies, those that could maintain eliminations results for a decade (2031-2040), in the absence of additional treatment. RESULTS:The model shows that the optimum elimination strategy is dependent on risk sharing behavior of the examined population. The necessary annual treatment coverage to achieve HCV elimination under 45% baseline CHC prevalence, without the simultaneous expansion of HR programs, ranges between 4.7-5.1%. Similarly, under 60% baseline CHC prevalence the needed treatment coverage varies from 9.0-10.5%. Increasing HR coverage from 40% to 75%, reduces the required treatment coverage by 6.5-9.8% and 11.0-15.0% under 45% or 60% CHC prevalence, respectively. In settings with ≤45% baseline CHC prevalence, expanding HR to 75% could prevent the disease from rebounding after elimination, irrespective of the type of the epidemic. In high chronic HCV prevalence, counseling interventions to reduce sharing are also needed to maintain the HCV incident cases in low levels. CONCLUSIONS:Harm reduction strategies have a vital role in HCV elimination strategy, as they reduce the required number of treatments to eliminate HCV and they provide sustainability after the elimination. The above underlines that HCV elimination strategies should be built upon the existing HR services, and argue for HR expansion in countries without services.

Project description:BackgroundHepatitis C virus (HCV) treatment uptake among people who inject drugs (PWID), a population with disproportionately high rates of HCV, remains low. Peers have been shown to positively impact a broad range of health outcomes for PWID. There is, however, limited data on the impact of PWID social network members on HCV treatment.MethodsHCV-infected PWID enrolled in an ongoing community-based cohort were recruited as "indexes" to complete an egocentric social network survey. The survey elicited from the index PWID a list of their network members and the index's perception of network member characteristics. Logistic regression analyses were conducted to compare individual and network factors associated with HCV treatment in the index PWID.ResultsAmong 540 HCV-infected PWID, the mean age was 55.7 years and the majority were black (87.2%) and male (69.8%). PWID reported a mean of 4.4 (standard deviation [SD] 3.2) network members, most of whom were relatives (mean 2.2 [SD 1.5]). In multivariable analysis, increasing index age and HIV infection were positively associated with HCV treatment, while drug use and homelessness in the preceding 6 months were negatively associated with HCV treatment. From a network perspective, having at least one network member who regularly talked with the index about seeing their doctor for HIV care was associated with HCV treatment (Adjusted Odds Ratio [AOR] 2.7; 95% Confidence Interval (CI) [1.3, 5.6]). Conversely, PWID who had at least one network member who helped them understand their HCV care were less likely to have been HCV treated (AOR 0.2; CI [0.1, 0.6).ConclusionHCV treatment uptake in this group of PWID appeared to be positively influenced by discussions with network members living with HIV who were in care and negatively influenced by HCV information sharing within PWID networks. These findings underscore the influence of peers on health seeking behaviors of their network members and emphasizes the importance of well-informed peers.

Dataset Information

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

Publications

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

Similar Datasets

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