SVR12 Rates Research Articles

Delayed clinical follow is not associated with lower SVR rates in an HCV-infected cohort in Mumbai, India

Delayed clinical follow is not associated with lower SVR rates in an HCV-infected cohort in Mumbai, India

Sofosbuvir/Velpatasvir fixed dose combination in Indian patients with chronic hepatitis c virus (HCV) infection: an open-label, single-arm, multicenter phase IV study

Background: This Phase IV post-marketing study was conducted to demonstrate the safety and efficacy of sofosbuvir/velpatasvir fixed-dose combination (FDC) in adult Indian patients with HCV infection as per the recommendation of the Drugs Controller General (India). Methods: This single-arm, open-label, multicenter study was conducted across 22 sites in 409 patients in India. All the eligible patients received once-daily sofosbuvir/velpatasvir (400mg/100mg) FDC for 12weeks. Safety was assessed by monitoring the adverse events (AEs) and efficacy was measured by the proportion of patients achieving sustained virological response (HCV RNA <15 IU/mL or undetectable) at 12weeks after the end of the treatment (SVR12). Results: Between October 2018 to June 2020, 409 patients were enrolled. Twenty patients discontinued the study due to consent withdrawal or lost to follow-up. The SVR12 rate was 90.8%. Sensitivity analysis showed consistent results with SVR12 rates of more than 93%. The combination was well tolerated and none of the AEs reported were related to the study drug, requiring dose reduction, or discontinuation of the study treatment. Conclusions: Once daily sofosbuvir/velpatasvir FDC for 12 weeks was found to be safe, well tolerated, and effective in patients with HCV infection. Trial Registration: The trial is registered at clinical trial registry of India with registration number CTRI/2018/08/015359. (CTRI Trial Data)

Recent Information on Pan-Genotypic Direct-Acting Antiviral Agents for HCV in Chronic Kidney Disease.

Hepatitis C virus (HCV) is still common in patients with chronic kidney disease. It has been recently discovered that chronic HCV is a risk factor for increased incidence of CKD in the adult general population. According to a systematic review with a meta-analysis of clinical studies, pooling results of longitudinal studies (n = 2,299,134 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD; the summary estimate for adjusted HR across the surveys was 1.54 (95% CI, 1.26; 1.87), (p < 0.0001). The introduction of direct-acting antiviral drugs (DAAs) has caused a paradigm shift in the management of HCV infection; recent guidelines recommend pan-genotypic drugs (i.e., drugs effective on all HCV genotypes) as the first-choice therapy for HCV, and these promise to be effective and safe even in the context of chronic kidney disease. The purpose of this narrative review is to show the most important data on pan-genotypic DAAs in advanced CKD (CKD stage 4/5). We recruited studies by electronic databases and grey literature. Numerous key-words ('Hepatitis C' AND 'Chronic kidney disease' AND 'Pan-genotypic agents', among others) were adopted. The most important pan-genotypic combinations for HCV in advanced CKD are glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL). Two clinical trials (EXPEDITION-4 and EXPEDITION-5) and some 'real-world' studies (n = 6) reported that GLE/PIB combinations in CKD stage 4/5 gave SVR12 rates ranging between 86 and 99%. We retrieved clinical trials (n = 1) and 'real life' studies (n = 6) showing the performance of SOF/VEL; according to our pooled analysis, the summary estimate of SVR rate was 100% in studies adopting SOF/VEL antiviral combinations. The drop-out rate (due to AEs) in patients on SOF/VEL ranged between 0 and 4.8%. Pan-genotypic combinations, such as GLE/PIB and SOF/VEL, appear effective and safe for HCV in advanced CKD, even if a limited number of studies with small sample sizes currently exist on this issue. Studies are under way to assess whether successful antiviral therapy with DAAs will translate into better survival in patients with advanced CKD.

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis.

Introduction:The sofosbuvir-velpatasvir single-tablet regimen (Epclusa) is a newly FDA-approved inhibitor of hepatitis C virus (HCV). This meta-analysis aimed to investigate the safety and efficacy of velpatasvir-sofosbuvir in the treatment of chronic HCV infection.Methods:A comprehensive literature search of PubMed, Cochrane CENTRAL, EMBASE and Web of Science was conducted. Data from eligible studies were pooled in a fixed-effect meta-analysis model, using Open-Meta and RevMan software’s.Results:Pooled data showed that velpatasvir-sofosbuvir achieved sustained virological response (SVR12) rates of 94.2% (95% CI 90.7–97.7%, P < .001) in 1277 patients. The addition of ribavirin did not significantly increase the SVR12 (RR = 1.03, 95%CI [0.95, 1.11]) in HCV genotype-1 patients and the SVR12 (RR = 1.09, 95%CI [0.86, 1.38]) in HCV genotype-2 patients. However, adding ribavirin significantly increased SVR12 (RR = 1.13, 95% CI [1.04, 1.23]) in genotype-3 patients.Conclusion:In conclusion, the 12-week regimen of sofosbuvir-velpatasvir was highly effective in HCV patients. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates.

A Phase 3 clinical trial validating the potency and safety of an innovative, extra-long-acting interferon in chronic hepatitis C.

Ropeginterferon alfa-2b is a novel mono-pegylated, extra-long-acting interferon. It is administered infrequently and showed good tolerability and clinical activity for the chronic hepatitis B or C treatment in our previous Phase 2 clinical trials. This study aims to validate the potency and safety of this novel agent in a Phase 3 chronic viral hepatitis setting. Patients with chronic hepatitis C genotype 2 were randomized to receive subcutaneous injections of ropeginterferon alfa-2b biweekly or the conventional pegylated interferon alfa-2b weekly for 24 weeks, combined with ribavirin. The primary endpoint was to assess the safety and antiviral potency of ropeginterferon alfa-2b by the non-inferiority in sustained virologic response at 12 weeks after treatment. A total of 222 patients were enrolled. Ropeginterferon alfa-2b group showed a favorable safety profile. Side effects that were generally associated with prior interferon therapies, including neutropenia, asthenia, fatigue, alopecia, dizziness, decreased appetite, nausea, flu-like symptoms including myalgia, pyrexia, and headache, and administration site reactions, were notably less in the ropeginterferon alfa-2b group. The cumulative incidence of adverse events of special interest was also notably higher in the control group. The primary endpoint was met and ropeginterferon alfa-2b showed a better SVR12 rate of 79.8% than 71.9% of the control group. Ropeginterferon alfa-2b is efficacious and has a favorable safety profile as compared with the conventional pegylated interferon alfa-2b. This study together with previous Phase 2 data validated ropeginterferon alfa-2b to be a new treatment option for chronic hepatitis C genotype 2.

HCV treatment in Sardinian HIV-HCV coinfected patients: a real-life perspective study on safety, efficacy, and immune reconstitution

ABSTRACT Background HIV-HCV co-infected patients have long been considered difficult-to-treat. The introduction of direct-acting antivirals (DAAs) changed this paradigm.We evaluated the efficacy and safety of DAA-based regimens and the impact of DAAs-induced HCV clearance on the immunological status in HIV-HCV co-infected patients. Research design and methods HIV patients starting HCV treatment with DAAs were included. Sustained virological response at 12 weeks after DAAs treatment (SVR12) was assessed. CD4+ and CD8+ blood cell count and CD4+/CD8+ ratio were recorded at baseline and six months post DAA treatment. We enrolled 201 patients, 76.1% males, median age 54 years, the most common genotypes 3 (29.8%) and 1a (29.4%), 40.3% with cirrhosis, 32.3% with prior interferon-based treatment. All patients were on antiretroviral treatment, 24.4% on methadone maintenance therapy and 22.6% on psychotropic drugs. Results SVR12 was 98.4%, the most common side effects were pruritus (8.4%), headache (7.4%) and fatigue (5.9%). An increase in CD4+ and CD8+ cell count was observed six months after completion of DAAs treatment, in particular in patients with low CD4+ cell count at baseline. Conclusions DAAs treatment resulted in high SVR12 rates, was well tolerated and Increased CD4+ and CD8+, especially in patients with low CD4+ cell count at baseline.

S1371 High SVR Rates, Regardless of Race or Socioeconomic Class, in Patients Treated With HCV DAAs in Community Practice Using a Specialized Pharmacy Team

Introduction: Approved HCV DAA regimens can cure nearly all patients; however, socioeconomic disparities may impact access and outcome. This study assesses socioeconomic factors, differences in insurance coverage and the drug prior auth process in HCV-infected patients managed in community practices partnered with a dedicated pharmacy team with expertise in liver disease. Methods: This IRB-approved, ongoing study captures data on a cohort of 2480 patients from community practices. Patients had chronic hepatitis C and were treated with DAA regimens selected by their physician. Median income is based on home zip code. The HCV Health Outcomes Centers (HOC) Network provides comprehensive patient management including a dedicated pharmacy support team with expertise in the prior auth process. Results: In this cohort, 60.1% were male, 49% were Hispanic Whites (HW), 37% were Non-Hispanic Whites (NHW), and 14% were Black. Eighty-seven percent of patients were treatment naïve, 74% were infected with genotype 1 virus and 63% had advanced fibrosis/cirrhosis (F3/F4=68.2% HW, 65.6% Blacks, 55.4% NHW). Figure depicts the distribution of socioeconomic characteristics by racial group. Forty percent of patients were on disability with the highest % in the Black group and less than 1/3 were employed full time, regardless of race/ethnicity. Medicare covered 42% of Black patients vs 32% of HW and NHW. The vast majority of HW (80%) and Blacks (75%) had a median income below the median income of Texas residents. Additionally, 75% of HW and 71% of Blacks had median income below the poverty level in Texas. Despite the above socioeconomic factors, 92% of all prior authorizations were approved upon first submission and patients received DAAs an average of 17 days from prescription. DAA therapy resulted in cure in 95.3% of patients (SVR=94.8% HW, 94.0% Blacks, 96.5% NHW). Conclusion: Despite having more advanced disease and more negative socioeconomic factors, > 94% of HW and Blacks patients were cured. Continued patient education and communication with the healthcare team can lead to high adherence and > 94% HCV cure rates regardless of race/ethnicity or underlying socioeconomic factors in the community setting.Figure 1.: Distribution of socioeconomic characteristics by racial group.

Efficacy and safety of direct-acting antivirals for HCV in patients with extrahepatic malignancies: real-life experience

BackgroundOutcome of HCV treatment with direct antiviral agents in malignant patients is questionable. The aim is to assess the safety and efficacy of DAAs in treatment of chronic HCV patients who received chemotherapy for malignancies.MaterialsRetrospective cohort study of 83 patients with HCV post chemotherapy receiving DAAs treatment compared to a matched group of 88 chronic HCV patients without cancer. Demographic, laboratory and abdominal ultrasound data, and SVR were taken for all patients.ResultsPatients’ data revealed mean age (52 years) and BMI (29). A total of 52% of HCV patients were females, and 83.6% were treatment naïve. Patients with cancer had higher FIB4 values and more cirrhosis (20.5% vs. 13.6%) with no statistical significance. Total bilirubin and HbA1C levels were significantly higher in HCV patients without cancer. All patients in either groups received SOF-based DAAs except 2 cases received PAR/OMP/RBV. SVR rate was very high and comparable between the two groups (100% and 97.7% in post chemotherapy and control groups) with no statistical difference. Mortality was represented in 23% in patients post chemotherapy with FIB4 score considered the only predictor for mortality.ConclusionDAAs have excellent efficacy in patients post chemotherapy. Further studies should be conducted for their concomitant use with chemotherapy.

Patients with Hepatitis C on Direct-Acting Antiviral Agents' Response to the Elimination Program in Dammam City within 2018-2020

Background: Hepatitis C virus (HCV) is a worldwide health challenge that imposes urgent interventions for prevention and control. We aimed to assess the response rate for the direct-acting antiviral agents (DAAs) regimen in HCV-infected patients attending the public health centers/hospitals in the Western region of Saudi Arabia. Methods and Results: A retrospective study was followed, including data from the electronic medical records of HCV-infected adult patients in the period 2018-2020. Patients underwent HCV health education and treatment with DAAs according to the regional protocols. The type of treatment regimens provided to the included patients was recorded with the outcome (respondent vs. non-respondent) after 12 weeks post completion of treatment (SVR12) based on negative results (or less than the minimum detection levels using the specified assay) of HCV-RNA detected by polymerase chain reaction. The SVR12 was used for predicting SVR as it was reported to be applicable as SVR24. All cases with discontinuations, treatment modifications, and/or deaths were excluded. Included were a total of 505 adult patients recorded in 13 primary healthcare units and hepatitis treatment specialty clinics of hospitals in the Eastern region of Saudi Arabia during the specified period of the study. The patients were aged 30–73 years (mean age of 48.1±9.1 years), of which 229(45.3%) were females and 276(54.7%) males. Most patients received sofosbuvir/daclatasvir (86.1%), followed by glecaprevir/pibrentasvir (11.5%), and elbasvir/grazoprevir (2.4%). Overall, the SVR rate was 97.4% in the study population. Sofosbuvir/daclatasvir had an SVR12 of approximately 98.4%, while the rate of glecaprevir/pibrentasvir was 93.1%. Conclusion: The present findings show an overall HCV cure rate of 97.4% of patients with HCV in response to the elimination program with DAAs in the Eastern region of Saudi Arabia, as indicated by high SVR12. This is an example of treating patients with HCV in a structured, supportive setting to help in the HCV elimination program.

High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway

Background and aims The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. Method This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). Results We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. Conclusion We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing.

High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus.

There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection. Patients treated with DAAs at our center during 2014-2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed. We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86-99%) for the entire study cohort, 100% [17/17; 95% CI: 82-100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79-98%] for the patients treated with LDV/SOF. Fisher's exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3-4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred. Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.

Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals-Results from the EuroSIDA study.

Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p= 0.55). In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.

Sofosbuvir-velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan.

Protease-free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir-velpatasvir in participants with HCV and compensated cirrhosis in Japan. This was a Phase 3, multi-center, open-label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir-velpatasvir (400mg/100mg) daily for 12weeks. Participants were treatment-naïve or treatment-experienced with interferon-based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12weeks after treatment (SVR12). Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance-associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on-treatment breakthrough or relapse occurred. Sofosbuvir-velpatasvir for 12weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia. Sofosbuvir-velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single-tablet regimen offers a highly effective, protease-inhibitor free regimen for treating HCV. gov Identifier: NCT04112303.

Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment.

Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. Methods: Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. Results: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC50 compared to wildtype. Conclusion: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.

The effectiveness and safety of direct-acting antivirals for hepatitis C virus treatment: A single-center experience in Saudi Arabia

BackgroundThe introduction of direct-acting antivirals (DAA) to treat the hepatitis C virus (HCV) overcame many drawbacks of interferon-based therapy. DAA achieved sustained viral response (SVR) rates above 90% and overcame many drawbacks of pegylated interferon regimens.The HCV genotype (GT) distribution varies by geographical area, with GT-4 being most prevalent in the Middle East region, including Saudi Arabia. Yet, the real-world evidence about using DAAs in the Saudi population is limited.Thus, the aim of this study to investigate the effectiveness and safety of DAAs in Saudi patients with HCV infection. MethodsA retrospective cohort study included patients treated with DAAs from 2015 to 2017 at a tertiary care hospital in Riyadh, Saudi Arabia. All patients with HCV treated with either ledipasvir plus sofosbuvir (LDS/SOF) ± ribavarin (RBV) or ombitasvir-paritaprevir-ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± RBV were included. Using a per-protocol analysis, the effectiveness outcome was the end-of-treatment response (EOTr) and Sustained virologic reponce12 weeks after competing the regimen (SVR12). The secondary safety outcome was the adverse event related to the therapy reported by the patients. ResultsA total of 97 patients were included; with the majority infected with GT-4 (64 %), followed by GT-1 (18 %), in addition to 8 % having a mixed GT (1 + 4). The EOTr and SVR12 rates were 98 % and 96 %, respectively. SVR12 was 94.4 % within the LDS/SOF ± RBV group and 97.7 % within the OBV/PTV/r ± DSV ± RBV group. Only 4 % had a response failure due to relapse or breakthrough, and all were infected with mixed GT1 + 4. Medications were well tolerated with minimal side effects, including vomiting, nausea, and weakness. ConclusionDAAs regimens are associated with high rates of SVR12 and are well tolerated with a good safety profile in Saudi HCV-infected patients.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

Background and aimsTreatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methodsInstitutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. ResultsAs previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. ConclusionThe retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Effectiveness and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir as a Hepatitis C Virus Infection Salvage Therapy in the Real World: A Systematic Review and Meta-analysis

IntroductionSofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) is the first direct-acting antiviral (DAA) therapy approved for patients who have previously failed a DAA-containing regimen including NS5A inhibitors. In clinical trials, SOF/VEL/VOX was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. However, the effectiveness and safety of SOF/VEL/VOX in the real world remained uncertain. We aimed to perform a systematic review and meta-analysis to assess the real world effectiveness and safety of SOF/VEL/VOX.MethodsWe systematically searched the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for relevant real world studies published before January 28, 2022. Patients with previous treatment failure who received SOF/VEL/VOX were included. The primary outcome was the percentage of patients achieving SVR12. Secondary outcome included adverse events (AEs) during treatment.ResultsFifteen studies with a total of 1796 HCV-infected patients with previous treatment failure were included. SVR12 rates were 93% (95% CI 91–95) in the ITT populations (n = 1517, 11 cohorts) and 96% (95% CI 95–97) in the PP populations (n = 1187, 10 cohorts). SVR12 rates were significantly higher in non-GT3-infected patients (OR = 2.29, 95% CI 1.23–4.27, P = 0.009) and non-cirrhotic patients (OR = 2.22, 95% CI 1.07–4.60, P = 0.03) than in GT3-infected patients and cirrhotic patients. Furthermore, the SVR12 rates of previous treatment of SOF/VEL were significantly lower than those of other regimens in both ITT and PP populations (P ≤ 0.001). Adverse events (AEs) were reported in 30% (228/760) of patients. Serious AEs (SAEs) were reported in 3.82% (29/760) of patients. The most frequently reported AEs were headache, asthenia, nausea, fatigue, and diarrhea, which were mostly mild in severity. AE-related treatment discontinuations were reported in 0.66% (5/760) of patients.ConclusionsConsistent with clinical trials, the real world evidence indicates that SOF/VEL/VOX is a well-tolerated and highly effective salvage therapy for HCV-infected patients with previous treatment failure. However, there may still be a risk of treatment failure for patients with GT3 infection, cirrhosis, or SOF/VEL treatment failure. The protocol of this study was registered at PROSPERO, registration no. CRD 42022306828.

Study the response of Qurevo (ombitasvir, paritaprevir, and ritonavir) in end-stage renal disease patients with hepatitis C virus

BackgroundOut of the 185 million people infected with hepatitis C virus (HCV) worldwide according to the World Health Organization (WHO), Egypt had the highest prevalence of HCV reaching 13% of its population with an estimated number of 12 million people. The prevalence of HCV infection among hemodialysis (HD) patients ranged from 6 to 60%. HD patients have an increased overall mortality risk if they have chronic HCV when compared to those without HCV infection. Treatment of HCV with the new direct-acting antiviral agent (DAA) therapy Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin in ESRD was approved in many countries compared to traditional HCV treatment that faced restrictions in the setting of chronic kidney disease (CKD).Aim of the studyTo evaluate the efficacy and safety of Qurevo/ribavirin regimen in HCV-infected HD patients.Patients and methodsA prospective cohort study evaluated the outcome of 12-week ombitasvir (NS5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir with ribavirin combination therapy for 50 HCV-infected HD patients, over a period of 15 months from December 2016 to February 2018. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) and after 24 weeks of therapy (SVR24).ResultsThe SVR12 rate was 96% (48/50); 2 patients (4%) were non-responders to treatment at SVR12, and another 2 (4%) were relapsers after SVR12. As regards the adverse events, the most frequent were fatigue/asthenia in 44 patients (88%) and worsening anemia (Hb dropped to < 10 g/dl) in 42 patients (84%). GIT upset occurred in 10 patients (20%), sleep disorders in 8 patients (16%), decreased appetite in 8 patients (16%), respiratory distress in 6 patients (12%), headache and dizziness in 6 patients (12%), and muscle spasms in 4 patients (8%). Itching (pruritus) occurred in 3 patients (6%). Death occurred in 4 patients (8%) after SVR24 most probably not due to DAA but may be due to myocardial infarction, pulmonary edema, severe hypotension on hemodialysis sessions, and shock due to blood loss in retroperitoneal hematoma following peritoneal dialysis not related to DAA therapy. Hepatic decompensation, hypersensitivity (angioedema), teratogenicity, and drug interactions did not occur in any patient (0%). Other events occurred in 11 patients (22%). They were parenchymal liver changes in ultrasound at the end of therapy after being normal before therapy (in 3 patients), thrombocytopenia, increased alkaline phosphatase, hiccough, deterioration of hypertension, urinary tract infection, lower limb cellulitis, vaginal bleeding, and chest infection (in 1 patient each). SVR12 was achieved in 100% of patients who had to stop or modify the ribavirin dose; this means that ribavirin absence did not affect the SVR in these patients.ConclusionOur results confirm the efficacy of Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin combination therapy in ESRD patients (on regular hemodialysis) with HCV infection with anemia as the most frequent adverse event.

Effectiveness of Ombitasvir with Paritaprevir/Ritonavir plus Ribavirin on the Treatment of Naïve Patients with Chronic Hepatitis C Virus Genotype 4

Background Direct-acting antivirals (DAAs) combination therapies from various mechanisms of action and families have been revolutionized the management landscape of chronic hepatitis C virus (HCV). Ombitasvir, paritaprevir with ritonavir (OBV/PTV/r) ± ribavirin (RBV) is approved to treat HCV genotype 4 (GT4) infection. Here, our objective was to delineate the efficacy and safety of OBV/PTV/r plus RBV in treating of Egyptian naïve patients infected with HCV GT4.&#x0D; Methods a cohort of 100 Egyptian patients infected with HCV GT4 was allocated and administered orally OBV/PTV/r with RBV. The primary endpoint of our study was a sustained virological response (HCV RNA &lt; 12 IU/mL) 12 weeks after the cessation of the treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT04378608.&#x0D; Results Among treatment naïve patients with OBV/PTV/r+ RBV, SVR12 rates achieved 97% (97/100) in overall patients. Regarding treatment failure, the regimen recorded 3 % had treatment failure (0 null-responses, 3 relapses). However, the most frequently common adverse events recorded were a headache (28%), fatigue (18%), asthenia (23%), nausea (19%) and dyspnea (14%).&#x0D; Conclusions The interferon-free regimen combination of OBV/PTV/r plus RBV achieved excellent SVR12 rates, 97%, with virologic outcome failures 3%, and it was generally safe and well tolerated for treating naïve patients infected with HCV GT4.

Telemedicine Improves HCV Elimination among Italian People Who Use Drugs: An Innovative Therapeutic Model to Increase the Adherence to Treatment into Addiction Care Centers Evaluated before and during the COVID-19 Pandemic.

Simple SummaryPeople who use drugs represent a category of patients to be prioritized for antiviral treatment for the purpose of hepatitis C elimination, due to their younger age and the major risk of viral transmission, acting as a virus reservoir. The treatment challenges for hepatitis C in this population are related to an ineffective linkage to care, poor adherence to treatment, and follow-up and the risk of re-infection. The COVID-19 pandemic has further exacerbated these conditions, increasing the concerns among clinicians regarding the effectiveness of their treatment. In our study, we describe a novel “patient-tailored” model-of-care for people who use drugs. The antiviral therapy was adapted to the needs of the patient and monitored remotely by a hepatological specialist, in order to decentralize the point of care within the addiction center. The study was conducted before and during the COVID-19 pandemic, clearly demonstrating the model’s high effectiveness in the linkage to care, adherence, and response to antiviral therapy.People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs.