Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model.
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ABSTRACT: Background
The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. Methods
An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. Findings
We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. Interpretation
Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. Funding
The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.
SUBMITTER: Dhiman R
PROVIDER: S-EPMC8529203 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:BACKGROUND:Directly acting antivirals (DAA) against hepatitis C virus (HCV) infection have facilitated sustained virologic response (SVR) rates >90% in clinical studies. Yet, real life data regarding DAA treatment in people who inject drugs (PWIDs) are scarce. We evaluated the effectiveness of glecaprevir/pibrentasvir (G/P) in difficult-to-treat PWIDs with presumed high risk of non-adherence to DAA therapy using the concept of directly observed therapy involving their opioid substitution therapy (OST) facility. METHODS:N = 145 patients (m/f: 91/54; median age: 41.1 (IQR 19.5) years; HCV-genotype (GT) 1/2/3/4: 82/1/56/5, GT3: 38.6%; cirrhosis: n = 6; 4.1%) treated with G/P were included. PWIDs at high risk for non-adherence to DAA therapy received HCV treatment together with their OST under the supervision of medical staff ("directly observed therapy", DOT). The effectiveness of G/P given as DOT in PWIDs with presumed high risk of non-adherence to DAA therapy was compared to patients with suspected "excellent compliance" in the "standard setting" (SS) of G/P prescription at a tertiary care center and self-managed G/P intake at home. Treatment duration was 8-16 weeks according to the G/P drug label. RESULTS:DOT-patients (n = 74/145; 51.0%) were younger than SS-patients (median 38.7, IQR 12.5 vs. median 50.6, IQR 20.3 years), all had psychiatric co-morbidities and most had a poor socioeconomic status. 50/74 (67.6%) reported ongoing intravenous drug use (IDU). SVR was achieved in n = 70/74 (94.6%) patients with n = 3 being lost to follow-up (FU) and n = 1 showing nonresponse to therapy. SS-patients achieved SVR in 97.2% (69/71) with n = 1 patient being lost to FU and n = 1 patient with GT3 showing HCV relapse. CONCLUSION:G/P given as DOT along with OST in PWIDs with high risk of non-adherence to DAA therapy resulted in similarly high SVR rates (94.6%) as in patients with presumed "excellent compliance" under standard drug intake.
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Project description:Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.
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Project description:BackgroundThe standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID.Methods and findingsINTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment.ConclusionsIntegrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV.Trial registrationClinicalTrials.gov.no NCT03155906.
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Project description:Background and aimsThe INTRO-HCV randomized controlled trial conducted in Norway over 2017-2019 found that integrated treatment, compared with standard-of-care hospital treatment, for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost-effectiveness of the INTRO-HCV intervention.DesignA Markov health state transition model of HCV disease progression and treatment with cost-effectiveness analysis from the health-provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality-adjusted life-years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia).Setting and participantsPWID attending community-based drug treatment centers for people with opioid dependence in Norway.MeasurementsIncremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness-to-pay threshold for Norway and lower (€20 000/QALY) threshold common among high-income countries.FindingsIntegrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost-effective against conventional and lower willingness-to-pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost-effective at the lower willingness-to-pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost-saving, respectively. Sensitivity analyses suggest integrated treatment was cost-effective at the lower willingness-to-pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost-saving with 60%-90% price reductions.ConclusionsIntegrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost-effective compared with standard-of-care referral pathways in Norway and may be cost-saving in settings with particular characteristics.
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Project description:Although the prevalences of HIV and HCV are significantly higher amongst PWID in India compared to the general population, the strains circulating within this group have not been well-characterized. Through subgenomic sequencing of viruses present in residual plasma from an HIV/HCV prevalence study conducted amongst PWID across five cities in India in 2016-2017, a total of N?=?498 HCV and N?=?755 HIV strains were classified from N?=?975 study participants. Considerable HCV diversity was identified, with different strains predominating in each region of the country. Overall, the most common strain was genotype 3a (39.0%), with genotypes 1a (26.9%), 1b (3.0%), 1c (0.2%), 3b (20.7%), 3i (2.0%), 4a (0.2%), 4d (1.0%), 6 (1.8%), 6n (4.8%), 6?v (0.2%) and one unclassifiable recombinant specimen (0.2%) also identified. The majority of the HIV specimens were subtype C (96.7%), although subtype A (0.4%), CRF01_AE (0.4%) and unique recombinant forms (URFs, 2.5%) were also detected. Notably, the geographical restriction of HIV subtype A and CRF01_AE, and HCV genotypes 4 and 6 to specific sites suggests distinct novel introductions of HIV and HCV into PWID populations, potentially via drug trafficking routes from neighboring countries where these strains are common.
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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.
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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.
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