High SVR Rates Research Articles

Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks

ObjectivesTo compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting. MethodsHCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6 × 106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared. ResultsIn the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (p = 0.044) and the respective relapse rates were 4.9% vs. 0.5% (p = 0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (p = 0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (p = 0.112). ConclusionHIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.

Real-world effectiveness of sofosbuvir/velpatasvir/voxilaprevir in 573 direct-acting antiviral experienced hepatitis C patients.

Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) provides a needed hepatitis C virus (HCV) antiviral option for direct-acting antiviral (DAA)-experienced patients. We evaluated the effectiveness of SOF/VEL/VOX for 12weeks in DAA-experienced patients with genotype 1-4 treated in clinical practice. In this observational cohort analysis from the Veterans Affairs' Clinical Case Registry, 573 DAA-experienced patients initiating SOF/VEL/VOX were included: 490 genotype 1, 20 genotype 2, 51 genotype 3 and 12 genotype 4. Rates of cirrhosis were 32.7%, 30.0%, 49.0% and 58.3%; rates of prior NS5A-experience were 100.0%, 95.0%, 90.2% and 100.0% for genotypes 1-4, respectively. Overall SVR rates were 90.7% (429/473), 90.0% (18/20), 91.3% (42/46) and 100.0% (12/12) for genotypes 1-4, respectively, and were 91.3% (274/300), 88.9% (16/18), 90.2% (37/41) and 100.0% (11/11) for those with prior NS5A+NS5B experience. For genotype 1, SVR rates were similar in patients with prior regimens of ledipasvir/SOF (90.6%, 298/329), elbasvir/grazoprevir (91.2%, 73/80) and ombitasvir/paritaprevir/ritonavir/dasabuvir (90.9%, 70/77). SVR rates in genotype 1, 2 and 3 patients with prior SOF/VEL experience were 78.9% (15/19), 86.7% (13/15) and 84.6% (11/13). In genotype 1-4 patients completing 12weeks of SOF/VEL/VOX, overall SVR rates were 95.1% (409/430), 89.5% (17/19), 93.3% (42/45) and 100% (12/12). In this diverse real-world cohort of heavily NS5A pretreated patients, SOF/VEL/VOX SVR rates in DAA-experienced patients were high across all genotypes. Genotype 1 patients who had prior experience with the most commonly prescribed NS5A regimens achieved similarly high SVR rates when retreated with SOF/VEL/VOX. For genotypes 1, 2 and 3, patients with prior SOF/VEL experience had lower SVR rates.

Real-world Australian data reflect very high sustained virologic response at 12 weeks with direct acting antiviral therapy for hepatitis C and suggests highly achievable even in those without an end-of-treatment response.

There are limited real-world data on the efficacy of direct acting antiviral (DAA) therapy for hepatitis C (HCV) in Australia. In this study, the efficacy of DAA therapy for HCV was compared between cirrhotic and non-cirrhotic cohorts. Patients without end-of-treatment response (EoTR) were observed to ascertain likelihood of achieving sustained virological response at 12 weeks post-treatment (SVR12). A total of 334 patients with HCV was included. Overall SVR12 was 96.7% with minimal differences in SVR12 between the cirrhosis and non-cirrhosis groups (95.7 and 97.3%). There were 20 patients (5.99%) that failed to achieve an EoTR of which 80.0% (n = 16) went on to achieve SVR12. These results suggest DAA therapy is effective with high rates of SVR12 even in patients that do not achieve an EoTR.

Evolution of HCV patient characteristics and DAA regimens in the German Hepatitis C Registry (DHC-R) in 2014 and 2015.

The urgent need in HCV-infected patients with liver disease mandated the rapid implementation of IFN-free DAA combination therapies following their regulatory approval in 2014 and 2015 without full knowledge of the optimal combinations and regimens. Investigating the evolution of the DAA utilization patterns and treatment outcomes could provide learnings for future situations. This was an analysis of a prospective observational database from the German Hepatitis C Registry (DHC-R) covering a period from May 2014 to September 2015. Adult patients had evidence of chronic HCV GT1 or GT4 infection and were treated with an IFN-free combination regimen of simeprevir (SMV) + sofosbuvir (SOF) or other IFN-free regimens: daclatasvir + sofosbuvir (DCV + SOF), ledipasvir/sofosbuvir (SOF/LDV), paritaprevir/r + ombitasvir ± dasabuvir (PrOD), with or without ribavirine (R). A total of 5496 subjects were followed during the period. During this period, clinical recommendations and treatment patterns evolved rapidly in response to new evidence from clinical trials and clinical routine and regulatory approval of additional regimens. High SVR12 rates were seen in this cohort, even in hard-to-treat patient subgroups. In the multivariate analysis, gender, age, advanced cirrhosis, and intensified treatment for cirrhotics were associated with treatment outcome. Despite limited knowledge of the optimal utilization of the newly approved DAA combinations and treatment durations as well as their comparative efficacy and safety profiles, high SVR rates were achieved regardless of the DAA combination. These outcomes were facilitated by the rapid adaptation of clinical recommendations. Future situations with high unmet medical need may follow a similar approach.

Equal treatment efficacy of direct-acting antivirals in patients with chronic hepatitis C and hepatocellular carcinoma? A prospective cohort study

ObjectiveThe treatment outcome of direct-acting antivirals (DAAs) in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is controversial. The current study aimed to address the treatment efficacy and safety of...

DAA-based treatment for HIV-HCV-coinfected patients: analysis of factors of sustained virological response in a real-life study.

The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen. We performed a multicentre retrospective cohort study, enrolling all 243 HIV-HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia. Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, P<0.001, and from 92 ±34.6 mg/dl to 109.4 ±73.7 mg/dl, P=0.002, respectively). The treatment with DAAs led to a high SVR12 rate in HIV-HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection.

Efficacy of direct-acting antiviral therapy for hepatitis C viral infection. Real-life experience in Bahrain.

Purpose: The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C viral (HCV) infection. This study aims to establish real-world treatment efficacy of Sofosbuvir-based (SOF-B) and Ombitasvir/Paritaprevir/Ritonavir-based (OPR-B) regimens.Patients and methods: This prospective, non-randomized observational real-life study was conducted in Salmaniya Medical Complex, Bahrain, and included consecutive patients with chronic HCV infection (genotypes 1–4) who were treated with direct-acting antivirals. Sustained virologic response to therapy was assessed at week 12 post end of treatment (SVR12).Results: Of the 167 patients included, 60.5% (n=101) were treated with SOF-B and 39.5% (n=66) with OPR-B regimens for 12 weeks (n=148; 88.6%) or 24 weeks (n=19; 11.4%). SVR12 was achieved in 156 (93.4%) patients, 4 patients failed to achieve SVR despite completion of treatment, and 7 patients discontinued treatment due to non-compliance and were included in the analysis on an intention-to-treat basis. There was no difference between SOF-B and OPR-B regimens (95/101; 94.1%) and (61/66; 92.4%), respectively (p=0.68). However, SVR12 rates were significantly higher in patients without liver cirrhosis (103/104; 99.0%) compared to patients with cirrhosis (53/63; 84.1%; p<0.001), and in patients who received 12-week-regimen (141/148; 95.3%) compared to those who received 24-week regimen (15/19; 78.9%; p<0.024). However, logistic regression analysis identified cirrhosis at baseline to be the only independent predictor of non-SVR12 (OR: 16.1, 95% confidence interval 1.96–131.91, p=0.01). Apart from Hb, INR, and ALP, all other laboratory parameter improved following treatment (p<0.05).Conclusion: Both SOF-B and OPR-B regimens achieved high SVR12 rates in this real-life cohort of patients with chronic HCV infection, similar to what is reported in other real-world studies. Cirrhosis was the only independent predictor of poor response.

Glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C genotype 1 or 2 infection: Results from a multicenter, real-world cohort study.

Glecaprevir (GLE) and pibrentasvir (PIB) are new direct-acting antiviral agents (DAAs) with pangenotypic inhibitors that respectively target the hepatitis C virus (HCV) NS3/4 protease and NS5A. The aim of this study was to evaluate the effectiveness and safety of combining GLE and PIB for patients with HCV genotype (GT) 1 or 2 infection in the clinical setting, including patients DAA-experienced or on hemodialysis. This multicenter, real-world, retrospective, cohort study consisted of 314 Japanese patients who were treated with GLE (300mg) and PIB (120mg) for a fixed 8- or 12-week duration. We evaluated the sustained virologic response rate 12weeks after the end of treatment (SVR12) and adverse events. Among the treated patients, 122 had GT1 and 192 GT2 infection. The overall SVR12 rates in the per-protocol populations were 99.2% (119/120) for GT1 and 98.9% (183/185) for GT2. High SVR12 rates were observed in almost all subgroups, including cirrhosis, receiving hemodialysis, or previous all-oral DAA groups treated with asunaprevir and daclatasvir (GT1b), ledipasvir/sofosbuvir (GT1), or sofosbuvir and ribavirin (GT2). Virological relapse occurred in only 1.0% (3/305) of the patients who completed treatment. The most common adverse events were pruritus and fatigue (>5% of patients). Serious adverse events were rare and discontinuation due to an adverse event was required for 1.6% of the patients. In this real-world cohort study, treatment with GLE/PIB achieved high SVR12 rates with a low rate of serious adverse events among patients with HCV GT1 or 2 infection.

Real-world effectiveness and safety of sofosbuvir/velpatasvir and ledipasvir/sofosbuvir hepatitis C treatment in a single centre in Germany.

BackgroundNewer direct-acting antiviral therapies are increasingly becoming the therapy of choice in patients with hepatitis C virus (HCV) infection. Here, we report the safety and effectiveness of sofosbuvir/velpatasvir (SOF/VEL) and ledipasvir/sofosbuvir (LDV/SOF) in real-world cohorts in Germany.MethodsPatients initiated on SOF/VEL 12 weeks or LDV/SOF 8, 12 or 24 weeks regimens in a single German centre were included in this study. Data on treatment outcomes and adverse events (AE) were analysed in patients with available sustained virologic response 12 weeks after cessation of treatment (SVR12) information overall and by subgroups.ResultsThis study included 115 patients who received SOF/VEL from July-2016 to July-2017, and 249 patients who received LDV/SOF from November-2014 to September-2015. Overall, SVR12 was achieved in 99% of patients on SOF/VEL ± ribavirin 12 weeks independent of HCV genotype, treatment history, or cirrhosis status, and in 96% of patients treated with LDV/SOF 8 weeks or LDV/SOF ± ribavirin 12 or 24 weeks. In genotype 1 treatment-naïve, non-cirrhotic patients, ≥99% achieved SVR12 across SOF/VEL and LDV/SOF regimens. Likewise, 100% of genotype 3-cirrhotic patients on SOF/VEL ± ribavirin regimens achieved SVR12. Grade 3/4 AE were reported in 13 (5.2%) patients on LDV/SOF and in 1 (<1%) patient on SOF/VEL.ConclusionOverall, SOF/VEL and LDV/SOF achieved high SVR rates in a broad patient population. We showed the effectiveness of SOF/VEL as a pan-genotypic regimen, and regardless of treatment history or cirrhosis status. Use of such therapies improves outcomes and contributes towards the global efforts to eradicate HCV.

FRI-251-Impact of hepatitis C treatment on patterns of drug use and subsequent treatment outcomes: High SVR rates despite increasing intravenous drug use in the post treatment period

FRI-251-Impact of hepatitis C treatment on patterns of drug use and subsequent treatment outcomes: High SVR rates despite increasing intravenous drug use in the post treatment period

Experience of a Portuguese Center: Effectiveness of Direct-Acting Antiviral Therapy for Hepatitis C.

In late 2014, Portugal implemented a national program for the treatment of patients with chronic hepatitis C with directactingantiviral agents. This program has made Portugal one of the first European countries to implement a structured measure oftreatment to eliminate this serious public health problem. The aim of this study was to assess the effectiveness of direct-acting antiviraltherapy in the treatment of patients with chronic hepatitis C virus infection. A retrospective observational study was conducted at Centro Hospitalar de Lisboa Ocidental on the nationalonline platform from December 2014 until February 2017 and included patients with hepatitis C virus infection who underwent treatment.The primary endpoint was sustained virologic response at least 12 weeks post treatment. Data was analyzed with the SPSS 17.0program. During the study period, 820 patients completed therapy and achieved sufficient follow-up time to assess sustained virologicresponse with an overall response rate of 97.2% (n = 797) and a response rate of 98.0%, 99.5%, 90.9%, 95.1% and 94.2% forgenotypes 1a, 1b, 2, 3 and 4, respectively. Data suggested that advanced fibrosis (F3/F4), human immunodeficiency virus co-infectionand treatment failure with interferon and ribavirin were not negatively related with sustained virologic response in our population.Most patients (80.1%) completed treatment with ledipasvir/sofosbuvir ± ribavirin. The most common adverse events were fatigue andinsomnia followed by headache and weight loss. Patients predominantly had genotype 1 infection which correlates with HCV distribution in Europe, but we found a majorproportion in genotype 4 which can be explained by immigration from African countries. Our patients' ages ranging from 22 to 90 years,reflected a new approach with no upper age limit. Direct-acting antivirals regimens resulted in remarkably high SVR rates compared tointerferon-based regimens, which were consistent with clinical trials data. Our data showed that direct-acting antiviral-based regimens are safe and have a high success rate in the treatment ofpatients with hepatitis C virus infection in a real-world setting.

Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection

BackgroundChronic hepatitis C virus (HCV) infection with genotypes (GT) 1 and 2 accounts for over 50% of HCV infections globally, including over 97% of all HCV infections in Japan. Here, we report an integrated analysis of efficacy and safety of 8-week treatment with the all-oral, fixed-dose combination of the direct acting antivirals (DAA), glecaprevir and pibrentasvir (G/P), in DAA-naïve Japanese and overseas patients without cirrhosis and with HCV GT1 or GT2 infection.MethodsData from 899 DAA-naïve patients without cirrhosis and with HCV GT1 or GT2 infection treated with G/P (300/120 mg) for 8 weeks in the six Phase 2 or 3 overseas or Japan-only clinical trials were included. All patients who received ≥ 1 dose of G/P were included in an intent-to-treat (ITT) analysis. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and safety of the 8-week regimen in the ITT population.ResultsOverall, SVR12 was achieved by 98.9% (889/899) of DAA-naïve patients without cirrhosis, including 99.2% (597/602) of GT1-infected and 98.3% (292/297) of GT2-infected patients. Less than 1% (2/899) of patients overall and no Japanese patients experienced virologic failure. SVR12 rate was > 97% for patients regardless of baseline characteristics, and common comorbidities or co-medications. Overall, < 1% (2/899) discontinued G/P due to an adverse event (AE) and 1.6% (14/899) of patients experienced a serious AE.Conclusions8-week G/P treatment is safe and efficacious in DAA-naive patients without cirrhosis and with HCV GT1 or GT2 infection, demonstrating high SVR12 rates regardless of baseline patient and disease characteristics.ClinicalTrials.gov identifiersThe trials discussed in this paper were registered with ClinicalTrials.gov as follows: NCT02707952 (CERTAIN-1), NCT02723084 (CERTAIN-2), NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02738138 (EXPEDITION-2).

Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy

People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%-96%) never injectors, 673 (92%, 95% CI 89%-93%) PWID not on OAT and 177 (89%, 95% CI 83%-92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p <0.001). Among ongoing drug users, 15 (17%) were lost-to-follow-up, and 3 (3.5%) became reinfected. In the per protocol analysis, 97% never injectors, 95% PWID not on OAT and 95% PWID on OAT achieved SVR12 (p = 0.246). After adjustment, ongoing drug use was associated with SVR12 (intention-to-treat) and OAT use was not. HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

No need to discontinue hepatitis C virus therapy at the time of liver transplantation.

ObjectivesDirect antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden.MaterialIn total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52–65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy.ResultsThere were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7–21), CTP-score 9.0 (range 5–10), creatinine 82.5 μmol/L (range 56–135, reference 60–105), bilirubin 33 μmol/L (range 16–79, reference 5–25) and PK-INR 1.5 (range 1.1–1.8). The median duration of DAA therapy was 60 days (range 18–132) pre-LT, 54 days post-LT (range 8–111 days) and in total 15.5 weeks (range 12–30 weeks).ConclusionInterferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.

The outcome of the sofosbuvir Based Therapy in the treatment of Hepatitis C Virus Genotype 4 in Egyptian patients

Background and aim There have been significant advancements during the last few years with large numbers of ongoing trials with various direct-acting antivirals (DAA) showing high potency against hepatitis C virus (HCV). The aim was to show the effectiveness and side effects of Sofosbuvir based therapy in the treatment of HCV genotype 4 in Egyptian patients and compare its results with the international results. Methods The study included 740 patients with chronic HCV. The study population consisted of three groups: Group (1): included 240 patients who were treated with sofosbuvir 400 mg plus Peginterferon α2a and weight-based ribavirin for 12 weeks. Group (2): included 250 patients who were treated with sofosbuvir 400 mg and weight-based ribavirin for 24 weeks. Group (3): involved 250 patients who were treated with sofosbuvir 400 mg and simeprevir 150 mg once daily for 12weeks. Results Sustained virological response (SVR) occurred in 83.3% of the triple therapy group. In the dual therapy group, SVR occurred in 64% of patients. In the Simeprevir-Sofosbuvir group, SVR was achieved in 96% of patients with a statistically significant difference among the studied groups (p=0.015). Multivariate logistic regression analysis showed that treatment with simeprevir and sofosbuvir was associated with higher rates of SVR with an odds ratio of 12.5. Serum creatinine shows a negative correlation with an odds ratio of 3.1; MELD score showed a negative correlation with an odds ratio of 1.5. Conclusion Sofosbuvir-based therapy has satisfactory results for the treatment of hepatitis C virus genotype 4 with lesser complications

Treatment of HCV Infection with Direct-Acting Antiviral Agents in Patients with HIV/HCV Co-Infection: A Systematic Review

Context: Hepatitis C virus (HCV) infection is a significant cause of chronic liver disease in patients with human immunodeficiency virus (HIV) infection. Introduction of HCV direct-acting antiviral agents (DAAs) revolutionized the treatment of hepatitis C in patients with HIV/HCV co-infection. In this study, we systematically reviewed the treatment of chronic HCV infection in patients with HIV/HCV co-infection. Evidence Acquisition: In this systematic review, electronic databases including PubMed, Scopus, ScienceDirect, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of “HCV”, “HIV” and “DAA”. Studies assessed the effectiveness of interferon-free HCV antiviral therapies in patients with HIV/HCV co-infection were evaluated for inclusion in the systematic review. Results: After the screening of 728 records, we included 33 articles in our study, and seven different HCV antiviral regimens were evaluated. Ten studies for sofosbuvir plus simeprevir (SVR ranged from 72.2% to 100%), eight studies for sofosbuvir plus ribavirin (SVR ranged from 51.6% to 91.6%), 12 studies for sofosbuvir/ledipasvir (SVR ranged from 88.8% to 100%), eight studies for sofosbuvir plus daclatasvir (SVR ranged between 84.6% and 100%), two studies for grazoprevir/elbasvir (SVR ranged from 86.6% to 96.5%), six studies for ombitasvir/paritaprevir/ritonavir plus dasabuvir (SVR ranged from 90.6% to 100%), and just one study for sofosbuvir/velpatasvir with 95.2% SVR rate. Conclusions: This study found that treatment of HCV infection with DAAs can result in high SVR rate in patients with HIV/HCV co-infection.

Real-world effectiveness and safety of sofosbuvir and ledipasvir with or without ribavirin for patients with hepatitis C virus genotype 1 infection in Taiwan.

BackgroundThe real-world data for the effectiveness and safety of sofosbuvir/ledipasvir (SOF/LDV) with or without ribavirin (RBV) in patients with hepatitis C virus genotype 1 (HCV-1) infection remain limited in Taiwan.MethodsA total of 273 chronic HCV-1 patients receiving 8, 12, or 24 weeks of SOF/LDV with or without RBV were enrolled. The sustained virologic response rate at week 12 off-therapy (SVR12) by evaluable population (EP) and per-protocol population (PP) were assessed for effectiveness. The treatment discontinuation rate due to adverse events (AEs) and serious AE rate were assessed for safety. Baseline patient characteristics and on-treatment HCV viral kinetics associated with SVR12 were analyzed.ResultsThe SVR12 rates by EP and PP analyses were 96.7% (95% confidence interval [CI]: 93.9%-98.3%) and 97.5% (95% CI: 94.8%-98.8%), respectively. The rates of treatment discontinuation due to AE and serious AE were 0.4% and 4.4%, respectively. Seven patients with true virologic failure were relapsers. In 2 patients who were lost-to follow-up, one expired at treatment week 3 due to pneumonia which was considered not related to treatment, and one declined follow-up at off-therapy week 4. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment.ConclusionsSOF/LDV with or without RBV for 8–24 weeks is well tolerated and achieves a high SVR12 rate in patients with HCV-1 infection in Taiwan.

Efficacy and safety of sofosbuvir-based therapy in hepatitis C virus recurrence post living donor liver transplant: A real life egyptian experience.

Direct acting antiviral has offered treatment of hepatitis C virus (HCV) recurrence post liver transplantation (LT) with an all-oral regimen for short duration, excellent safety profile, and high sustained virological response (SVR). The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF)-based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post living donor LT (LDLT). Patients with HCV-G4 recurrence post-LDLT were recruited from National Committee of Control of Viral Hepatitis, Egypt, from November 2014 to May 2017. They received different SOF-based regimens according to the treatment protocols available during this period. Patients' outcome and Adverse effects (AE) were evaluated. One hundred ninety patients (170 males, mean age 56.8 ± 7.9 years) were included. Calcineurin inhibitors were the main immunosuppression used (173 patients). Out of 190, 119 (62.6%) received SOF/ribavirin (RBV), 38 (20%) SOF/simeprevir (SMV), 22 (11.6%) SOF/daclatasvir (DSV)/ ± RBV, and 11 (5.8%) received SOF/LDV/ ± RBV. Overall SVR12 was 89.5%, 84.9% in SOF/RBV group, 94.7% in SOF/SMV, 100% in SOF/DCV, and 100% in SOF/LDV with no statistically significant difference ( P = 0.104). The AE reported were as follows: anemia (n = 65, 34.4%) mainly in SOF/RBV group, transient hyperbilirubinemia during SOF/SMV in 13 patients (34%), mild Acute cellular rejection in eight patients (4.2%), and hepatocellular carcinoma in two patients (1%) mainly driven by underlying liver condition. Two deaths were unlikely related to HCV therapy. Different SOF-based regimens were effective with high SVR12 rates in a difficult-to-treat population, recurrent HCV post LDLT.

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotype 6 in Southwest China: Real-world experience of a retrospective study.

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment-naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF-based DAAs therapy, including SOF 400mg plus daclatasvir (DCV) 60mg daily or SOF 400mg plus velpatasvir (VEL) 100mg daily for 12weeks. The sustained virological response 12weeks after treatment (SVR12) was 100% (60/60) in treatment-naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P=0.014) and week 24 (P<0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P<0.001). SOF-based therapy was well-tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment-naïve patients with HCV GT6 without liver cirrhosis.

2224. Receipt and Virologic Outcomes of HCV Direct-Acting Antivirals by Alcohol Use and HIV Status

BackgroundThe impact of alcohol use and HIV infection on receipt of direct-acting antiviral (DAA) therapy and subsequent cure of chronic hepatitis C virus (HCV) is unknown.MethodsUsing the Veterans Health Administration (VA) Birth Cohort (>4.5 million patients born 1945–1965), we performed a cohort study among HCV RNA+ patients with at least one outpatient visit between 1 January 2014 and 31 May 2017; laboratory values were assessed through 30 November 2017. Alcohol use (abstinent, lower risk drinking, hazardous/binge drinking, diagnosis of alcohol use disorder [AUD]) was assessed in the year prior to the initial outpatient visit based on Alcohol Use Disorders Identification Test-Consumption questionnaire scores and validated ICD AUD codes. We defined DAA receipt based on filled prescriptions and achievement of HCV cure as sustained virologic response ≥12 weeks after treatment (SVR12). We calculated frequency of DAA receipt and SVR12 by alcohol use category and HIV status. We estimated associations between alcohol use and SVR12 by HIV status using logistic regression.ResultsAmong 134,491 HCV RNA+ patients with known alcohol use status, 3,670 (3%) were HIV+. More HIV+ patients were dispensed DAA therapy than uninfected persons (53.6% vs. 49.5%; P < 0.0001). Abstinent and lower risk drinkers were more likely to receive DAAs than hazardous/binge drinkers or those with an AUD (52.9%, 51.5%, 47.1%, 44.6%, respectively; P < 0.0001, Figure 1). While high SVR12 rates were observed across all alcohol use categories (range, 88.8–92.4% HIV+; 90.1–93.2% uninfected), those with AUD experienced modestly lower rates of SVR12 compared with abstinent individuals (89.1% vs. 92.1% HIV+; 90.1% vs. 91.6% HIV−, Figure 2). After adjusting for age, FIB-4, BMI, and hepatic decompensation, HIV− patients with an AUD were significantly less likely to achieve SVR12 compared with abstinent patients (OR, 0.88; 95% CI 0.81–0.94, Figure 3). ConclusionHIV+ patients and abstinent or lower risk drinkers were more likely to receive DAAs compared with uninfected patients and hazardous/binge drinkers or those with an AUD. High SVR12 rates were observed across all alcohol categories. These findings indicate a potential role for alcohol interventions along with HCV care and treatment.Disclosures All authors: No reported disclosures.