Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort

Rossi, Carmine; Butt, Zahid A; Wong, Stanley; Buxton, Jane A.; Islam, Nazrul; Yu, Amanda; Darvishian, Maryam; Gilbert, Mark; Wong, Jason; Chapinal, N.; Binka, Mawuena; Alvarez, Maria; Tyndall, Mark; Krajden, Mel; Janjua, Naveed Z.

doi:10.1016/j.jhep.2018.07.025

Cited by 111 publications

(96 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although, it has been shown that IDU and OST could significantly reduce the SVR, in our study these factors were not associated with treatment effectiveness. In a recent study, it has been shown that reinfection rate is higher among recent IDU compared to past IDU . In the current study, in the LDV/SOF ± RBV multivariable model; after adjusting for other characteristics, past IDU and OST were significantly associated with higher SVR achievement (Figure ).…”

Section: Discussionsupporting

confidence: 48%

“…In a recent study, it has been shown that reinfection rate is higher among recent IDU compared to past IDU. 28,45 In the current study, in the LDV/SOF ± RBV multivariable model; after adjusting for other characteristics, past IDU and OST were significantly associated with higher SVR achievement ( Figure 2). This finding highlights the need for harm reduction services and OST programmes among current IDUs.…”

Section: Yesmentioning

confidence: 60%

See 1 more Smart Citation

Loss to follow‐up: A significant barrier in the treatment cascade with direct‐acting therapies

Darvishian

Wong

Binka

et al. 2019

Journal of Viral Hepatitis

Self Cite

View full text Add to dashboard Cite

Effectiveness of direct‐acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow‐ups. Here, we evaluate loss to follow‐up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV‐positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow‐up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV‐treated patients. Overall, 453 (10.1%) individuals were lost to follow‐up. Higher loss to follow‐up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow‐up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow‐up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow‐up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

show abstract

Section: Discussionsupporting

confidence: 48%

Section: Yesmentioning

confidence: 60%

Loss to follow‐up: A significant barrier in the treatment cascade with direct‐acting therapies

Darvishian

Wong

Binka

et al. 2019

Journal of Viral Hepatitis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Data on reinfection in the DAA era are emerging. We have recently shown that recent PWID had higher reinfection rates compared to past PWID and those not injecting . In the current study, some individuals who had a positive RNA test following a negative test while on treatment or soon after the end of treatment followed by a positive RNA test before or at 10 weeks after the end of treatment are considered to have failed treatment.…”

Section: Discussionmentioning

confidence: 78%

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy

et al. 2019

Self Cite

View full text Add to dashboard Cite

We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population‐based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off‐OAT/RIDU), off OAT/past IDU (off‐OAT/PIDU), off OAT/no IDU (off‐OAT/NIDU), on OAT/IDU (on‐OAT/IDU), and on OAT/no IDU (on‐OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off‐OAT/RIDU, 598 off‐OAT/PIDU, 3,515 off‐OAT/NIDU, 609 on‐OAT/IDU, and 171 on‐OAT/NIDU. The majority were male patients (64%‐74%) and aged ≥50 years (58%‐85%). The SVRs for off‐OAT/RIDU, off‐OAT/PIDU, off‐OAT/NIDU, on‐OAT/IDU, and on‐OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off‐OAT/RIDU, on‐OAT/IDU, male sex, cirrhosis, treatment duration <8 weeks, treatment duration 8 weeks, and treatment with SOF/VEL were associated with not achieving SVR. Conclusion: In this large real‐world cohort, PWID and/or those on OAT achieved high SVRs, although slightly lower than people not injecting drugs. This finding also highlights the need for additional measures to prevent loss to follow‐up and overdose‐related deaths among PWID.

show abstract

“…27 In a large population-based cohort (British Columbia Hepatitis Testers Cohort) enrolling 4114 individuals, 40 subjects experienced an HCV re-infection. 28 Moreover, our population was at low probability of re-infection, since the presumed duration of HCV infection was very long (at least 12 years). Instead, patient #6 harboured different HCV 1 subgenotypes (1b and 1a respectively) before the start of the DAA regimen and at relapse; therefore, in this case, we can hypothesize a re-infection with another subgenotype of HCV, although an erroneous identification of the HCV subgenotype before the start of DAA may also be possible.…”

Section: Discussionmentioning

confidence: 92%

“…In a large French AIDS cohort on 3406 patients, HCV re‐infections occurred in 73 with an incidence of 2.52%‐2.90% patients‐year . In a large population‐based cohort (British Columbia Hepatitis Testers Cohort) enrolling 4114 individuals, 40 subjects experienced an HCV re‐infection . Finally, of great interest were the results of a meta‐analysis evaluating the risk of late relapse or HCV re‐infection after achieving a sustained virological response: in the 43 studies evaluating 7969 HCV‐monoinfected patients, the pooled recurrence rate was 1.85/1000 events/person per year of follow‐up (PYFU; 95% confidence interval [CI]: 71‐3.35); in the 14 studies evaluating 771 HCV‐monoinfected “high‐risk” patients (intravenous drug users or prisoners), the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07‐33.46); in the four studies evaluating 309 HIV/HCV coinfected patients, the pooled recurrence rate was 32.02/1000 PYFU (95% CI, 0.00‐123.49) …”

Section: Discussionmentioning

confidence: 99%

Hepatitis C late relapse in patients with directly acting antiviral‐related sustained virological response at week 12

Pisaturo¹,

Minichini²,

Starace³

et al. 2019

Liver International

View full text Add to dashboard Cite

Aim The aim of the present study was to identify, among the patients with failure to DAA regimen, those with a late relapse (after the achievement of a sustained virological response at week 12) and to characterize the clinical, epidemiological and virological features of these patients. Material and methods A total of 129 HCV patients with non‐response to an IFN‐free regimen were enrolled. Sanger sequencing of NS3, NS5A and NS5B was performed at failure by home‐made protocols. Results Of the 129 patients enrolled, 8 (6.2%) experienced a breakthrough, 15 (11.7%) non‐response, 99 (76.7%) a relapse by week 12 after the end of DAA therapy, and 7 (5.4%) a late relapse (after week 12; median 24 weeks, range 24‐72). For two of the seven patients with a late relapse, a serum sample collected before the start of the DAA regimen was available; phylogenetic analysis showed no change in sequences of NS3, NS5A and NS5B regions, suggesting a reactivation of the initial HCV strain; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re‐infection cannot be excluded. Conclusions Although a late relapse is infrequent, the study suggests a post‐treatment follow‐up of 72 weeks.

show abstract

Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort

Cited by 111 publications

References 40 publications

Loss to follow‐up: A significant barrier in the treatment cascade with direct‐acting therapies

Loss to follow‐up: A significant barrier in the treatment cascade with direct‐acting therapies

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy

Hepatitis C late relapse in patients with directly acting antiviral‐related sustained virological response at week 12

Contact Info

Product

Resources

About