Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial

Grebely, Jason; Dalgård, Olav; Conway, Brian; Cunningham, Evan B; Bruggmann, Philip; Hajarizadeh, Behzad; Amin, Janaki; Bruneau, Julie; Hellard, Margaret; Litwin, Alain H.; Marks, Philippa; Quiene, Sophie; Siriragavan, Sharmila; Applegate, Tanya; Swan, Tracy; Byrne, Jude; Lacalamita, Melanie; Dunlop, Adrian; Matthews, Gail V.; Powis, Jeff; Shaw, David R.; Thurnheer, Maria Christine; Weltman, Martin; Kronborg, Ian; Cooper, Curtis; Feld, Jordan J.; Fraser, Chris; Dillon, John; Read, Phillip; Gane, Ed; Dore, Gregory J.

doi:10.1016/s2468-1253(17)30404-1

Cited by 243 publications

(202 citation statements)

References 36 publications

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“…The use of HCV testing interventions such as alerts and patient solicitation methods has demonstrated improvement in screening and diagnosis rates in some centres . Our finding of excellent outcomes in PWID with no increase in LTFU compared to the general population supports current guidelines that ongoing drug should not preclude treatment …”

Section: Discussionsupporting

confidence: 73%

Real‐world outcomes of unrestricted direct‐acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience

Haridy

Wigg

Muller

et al. 2018

Journal of Viral Hepatitis

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In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.

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Section: Discussionsupporting

confidence: 73%

Real‐world outcomes of unrestricted direct‐acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience

Haridy

Wigg

Muller

et al. 2018

Journal of Viral Hepatitis

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“…Previous analyses of DAA regimens have demonstrated high adherence to treatment in the overall chronic HCV‐infected patient population, including those who were on opioid substitution therapy (OST) and people who use drugs (≥95% and ≥90% respectively). Some studies have suggested that adherence to DAA therapy decreases with increased treatment duration .…”

Section: Introductionmentioning

confidence: 99%

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Brown

Welzel

Conway

et al. 2019

Liver International

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Background & Aims Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non‐adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non‐adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non‐adherence on sustained virological response at post‐treatment week 12 (SVR12) rates in HCV genotype (GT) 1‐6‐infected patients. Methods Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non‐adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent‐to‐treat (ITT) population and modified ITT (mITT) population, which excludes non‐virological failures. Results Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non‐adherence to G/P therapy (OR: 2.38; 95% CI: 1.13‐5.01; P = .022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P = .047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively. Conclusions Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment. Clinical trials registration NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717.

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“…Treatment uptake has been historically low among PWID prior to the introduction of new direct‐acting antivirals (DAA) treatments . However, there is now good evidence that HCV treatment is safe and effective among PWID . The latest international guidelines now recommend treatment for all PWID.…”

Section: Introductionmentioning

confidence: 99%

High response and re‐infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme

Schulkind

Stephens

Ahmad

et al. 2018

Journal of Viral Hepatitis

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Summary To achieve WHO hepatitis C virus (HCV) elimination targets by 2030, mathematical models suggest there needs to be significant scale‐up of treatment among people who inject drugs (PWID). We tested whether people who actively inject drugs can be recruited and treated successfully through a community needle and syringe programme (NSP), and assessed rates of re‐infection. 105 HCV RNA positive participants were enrolled prospectively. Participants were recruited from the largest NSP in Dundee over 42 months. 94/105 individuals commenced treatment. Genotype 1 (G1) individuals (n = 37) were treated with peg‐interferon+ribavirin+Simepravir/Telaprevir. Genotype 2/3 (G2/3) (n = 57) received peg‐interferon+ribavirin. Weekly study visits took place within the NSP. Mean age of participants was 34.0 years (SD 6.9), 71.3% (61/94) were male. One in five (20/94) participants were homeless. 68.1% (64/94) were on OST (opiate substitution therapy) at enrolment; participants injected median 6.5 times/wk. In terms of clinical outcomes, >80% treatment adherence was 71.3% (67/94). There was no difference in SVR‐12 rates by genotype: 81.0% (30/37) for G1 and 82.5% (47/55) for G2/3. At 18 months post‐treatment, 15/77 participants were reinfected, followed up over 69.8 person‐years, yielding a re‐infection rate of 21.5/100 person‐years (95% CI 13.00‐35.65). This trial demonstrates that HCV treatment can be delivered successfully to the target population of treatment as prevention strategies. We report higher rates of re‐infection than existing estimates among PWID. Scale‐up of HCV treatment should be pursued alongside a comprehensive programme of harm reduction interventions to help minimize re‐infection and reduce HCV transmission.

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Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial

Abstract: Gilead Sciences.

Cited by 243 publications

References 36 publications

Real‐world outcomes of unrestricted direct‐acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience

Real‐world outcomes of unrestricted direct‐acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

High response and re‐infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme

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