Started Hepatitis C Virus Treatment Research Articles

Progress of Hepatitis C elimination in Viennese people living with HIV after two decades of increasing cure rates

Background & Aims Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs). We assessed temporal trends in patient characteristics, transmission risks, treatment initiation, and cure rates in eras of IFN, restricted DAA-access, and unrestricted DAA-access in Viennese HCV/HIV-coinfected patients (HIV/HCV). Methods Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. Results Of all N = 508 HIV/HCV, 78% (398/508) were male and the mean age was 41.8 ± 9.5 years. ‘People-who-inject-drugs’ (PWID) accounted for 61% (311/508), while 31% (156/508) were ‘men who have sex with men’ (MSM). In the IFN-era, restricted DAA-era and unrestricted DAA-era, N = 152, N = 129, and N = 227 HCV treatments were started and 49% (74/152), 95% (122/129), and 88% (200/227) achieved sustained virologic response, respectively. Treatment during the IFN-era was a strong predictor for virologic non-response (aOR 12.69; 6.93–23.24) and loss-to-follow-up (aOR 6.12; 2.99–12.54), while virologic non-response was less common in ‘MSM’ (aOR 0.28; 0.13–0.62). Ninety three percent (50/54) of the observed HCV reinfections occurred in the unrestricted DAA-era. A substantial increase in ‘MSM’ transmission was observed since 2010 with 66% (107/161) in the DAA-era versus 15% (49/330) prior to the DAA-era. Conclusions HCV cure rates in Viennese HIV patients increased from 49% in the IFN-era to 88–95% in the DAA-era. MSM-related risk behaviour and reinfections became the key challenges towards HCV elimination in HIV-coinfected patients.

Barriers to Hepatitis C Virus Care and How Federally Qualified Health Centers Can Improve Patient Access to Treatment.

Despite the availability of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) treatment, disparities in HCV care and treatment persist for underserved populations due to demographic-based and insurance-based barriers. We aim to examine the effect of barriers on HCV treatment access for a federally qualified health center (FQHC) population. We retrospectively evaluated medical records of adults diagnosed with chronic HCV at an FQHC clinic from 2016 to 2020 with follow-up through 2021. Univariate and bivariate analyses were used to describe the patient population and significant associations between predictors of linkage to HCV care and treatment access. Adjusted multivariate logistic regression analyses were used to identify predictors of starting HCV treatment. Of 279 total patients with chronic HCV, 162 patients started treatment (58%), 138 patients (50%) completed treatment, and 99 patients (35%) achieved sustained virological response (SVR). Of the total patients, 145 (52%) were seen by their primary care physician (PCP) for their HCV care and treatment, and 134 (48%) were seen by a provider that specializes in management and treatment of HCV (HCV provider). Patients seen by an HCV provider in addition to their PCP were more likely to have had their prior authorization requests for HCV treatment denied by their insurance providers than patients seen only by their PCP for HCV care (30% vs. 14%, P = 0.001). We believe that this discrepancy stems from two issues. One, prior authorizations are reviewed by insurance providers who are not specially trained in HCV management, so the verbiage used perplexes these reviewers, possibly causing them to issue denials. Two, insurance providers often require HCV genotype testing for DAA medication eligibility, and HCV providers order genotype tests for patients only when HCV treatments have failed to cure patients, so this requirement becomes another barrier to DAA medications. Patients who spoke a non-English language, lived in the USA for less than 10 years, and showed inability to pay for treatment had received treatment despite these characteristics being common barriers to HCV treatment. On multivariate regression, factors independently associated with patients starting treatment included prior denial for DAA medication (odds ratio (OR), 8.88; 95% confidence interval (CI), 3.22 - 24.6; P < 0.001) and being seen by an HCV provider (OR, 24.8; 95% CI, 11.7 - 52.5; P < 0.001). However, the most significant barrier to HCV treatment access for the FQHC population was eligibility restrictions from insurance providers. Demographic-based barriers (e.g., age, race, and income) often impede HCV care and treatment, but insurance-based barriers are the greatest challenge currently that affects treatment outcomes in our study population. Removing these restrictions would, in our opinion, help to increase treatment levels to underserved populations.

Factors Associated with Sustained Virologic Response to Hepatitis C Treatment in a Homeless-Experienced Cohort in Boston, 2014-2020.

Engaging people experiencing homelessness or unstable housing in hepatitis C virus (HCV) treatment is critical to achieving HCV elimination. To describe HCV treatment outcomes, including factors associated with retention through the treatment cascade, for a cohort of individuals treated in a homeless health center in Boston. Retrospective cohort study. All individuals who initiated HCV treatment with Boston Health Care for the Homeless Program's HCV treatment program between January 2014 and March 2020 (N = 867). The primary outcome was sustained virologic response (SVR), defined as an HCV ribonucleic acid (RNA) level ≤ 15 IU/mL at least 12 weeks after treatment completion. We used multivariable logistic regression to examine the association between baseline variables and SVR. Process-oriented outcomes included treatment completion, assessment for SVR, and achievement of SVR. Of 867 individuals who started HCV treatment, 796 (91.8%) completed treatment, 678 (78.2%) were assessed for SVR, and 607 (70.0%) achieved SVR. In adjusted analysis, residing in stable housing (OR 3.83, 95% CI 1.85-7.90) and age > 45 years old (OR 1.53, 95% CI 1.04-2.26) were associated with a greater likelihood of achieving SVR. Recent drug use (OR 0.63, 95% CI 0.41-0.95) was associated with a lower likelihood of SVR. Age, housing status, and drug use status impacted retention at every step in the treatment cascade. A large proportion of homeless-experienced individuals engaging in HCV treatment in a homeless health center achieved SVR, but enhanced approaches are needed to engage and retain younger individuals, those with recent or ongoing substance use, or those experiencing homelessness or unstable housing. Efforts to achieve HCV elimination in this population should consider the complex and overlapping challenges experienced by this population and aim to address the fundamental harm of homelessness itself.

Longitudinal Assessment of the Enhanced Liver Fibrosis Score in the Era of Contemporary HIV and Hepatitis C Virus Treatment.

The trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy. We assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1-2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1-2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count). INSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment. The apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential.

Disparities in the quality of care for chronic hepatitis C among Medicare beneficiaries.

PurposeChronic hepatitis C virus (HCV) infection is an important public health concern. Limited information exists on disparities in the quality of HCV care. We examine disparities in genotype or quantitative HCV ribonucleic acid testing before and after starting HCV treatment, and screening for hepatocellular carcinoma (HCC) in HCV patients with cirrhosis.MethodsThis national study included Medicare beneficiaries with HCV between 2014 and 2017. We used bivariate probit to estimate the probability of receiving recommended tests before and after HCV treatment by patient race/ethnicity, urban/rural residence, and socioeconomic status. We used multivariate logistic regression to estimate adjusted odds ratios (aOR) of HCC screening among beneficiaries with cirrhosis by patient factors.FindingsOf 41,800 Medicare patients with HCV treatment, 93.47% and 84.99% received pre- and post-treatment testing. Patients in racial minority groups had lower probabilities of pre- and post-treatment testing than whites. Rural residents were less likely to receive a post-treatment test (Coef. = -0.06, 95% CI: -0.11, -0.01). Among HCV patients with cirrhosis, 40% (24,021) received at least one semi-annual HCC screening during the study period. The odds of HCC screening were 14% lower in rural than in urban patients (aOR = 0.86, 95% CI: 0.80, 0.92), lower in African Americans (aOR = 0.93, 95% CI: 0.90, 0.96), but higher among Hispanics than in whites (aOR = 1.09, 95% CI: 1.04, 1.15). There was no significant association between ZIP-level income or education and HCC screening.ConclusionsDisparities in the quality of HCV care existed by patient race/ethnicity, urban/rural residence, and socioeconomic status. Continued efforts are needed to improve the quality of care for all HCV patients—especially rural patients and racial/ethnic minorities.

Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain.

The burden of hepatitis C virus (HCV) infection among marginalized people in Spain is high, despite the fact that HCV prevalence has decreased in recent years. We aimed to assess the effectiveness of a simplified point-of-care (PoC) model for screening for active HCV infection via a mobile unit and subsequent linkage to care with the assistance of navigators. We carried out a prospective study on 2001 participants from Madrid, Spain. A nurse and a navigator/educator screened for hepatitis C in a mobile unit, using the OraQuick HCV Rapid Antibody Test and Xpert HCV VL Fingerstick assay. Participants with active HCV were referred to the hospital the same day with a navigator for evaluation and treatment of HCV. Overall, 1621 (81%) participants had not been exposed to HCV, 380 (18.9%) were positive for HCV antibodies, and 136 (6.8%) had active hepatitis C. Among the latter, 134 (98.5%) received the HCV screening results, 133 (97.8%) had an appointment at the hospital, 126 (92.8%) were seen by a physician once they were at the hospital, and 105 (77.2%) started HCV treatment. Being over 50 years old and a person who uses drugs, particularly people who inject drugs (PWID), was directly associated with active hepatitis C (p<0.05). PWID were the only patients with HCV reinfection (4.3% in people without recent injecting drug use and 5.9% in people with recent injecting drug use). Among PWID, no income and daily alcohol intake were also directly associated with active hepatitis C. People with recent injecting drug use showed the lowest rates of attendance at the hospital (91.8%) and starting HCV treatment (70.4%). HCV screening using a two-step PoC-based strategy and its linkage to care was extremely efficient for identifying and treating marginalized people with active hepatitis C, thanks to the use of a mobile unit with personnel and technical equipment, an interdisciplinary team, and collaboration between institutions.

The Impact of Current Opioid Agonist Therapy on Hepatitis C Virus Treatment Initiation Among People Who Use Drugs From the Direct-acting Antiviral (DAA) Era: A Population-Based Study.

Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset. The British Columbia Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in British Columbia, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT. In total, 13 803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2704/5770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT had started HCV treatment. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95% confidence interval {CI}, 1.50, 2.26]). Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.

Hepatitis C treatment uptake among patients who have received methadone substitution treatment in the Republic of Georgia

ObjectivesThere is a dearth of research on hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWIDs) and receive methadone substitution treatment (MST) in Eastern Europe and Central Asia countries. This study contributed to addressing that gap. We examined and identified factors that may affect HCV treatment uptake among PWID who received MST in the Republic of Georgia. Study designThe design of the study is retrospective cohort study. MethodsWe conducted HCV care cascade analysis by matching the data from the web-based national hepatitis C program registry (ELIM C) and the MST treatment database between January 1, 2015, and December 31, 2018. Using the World Health Organization's (WHO) Consensus HCV cascade of care (CoC) global instrument, we assessed the progress made toward the country's 2020 and WHO's 2030 hepatitis C elimination targets for the subpopulation of MST patients. ResultsOverall, 10,498 individuals have been dispensed methadone during the study period. A total of 6828 MST beneficiaries had HCV screening, of whom 5843 (85.6%) tested positive; 5476 (93.7%) were tested for HCV viremia, and 5275 (96.3%) were confirmed with chronic HCV infection. More than 75% (n = 4000) of HCV-infected MST patients initiated HCV treatment, and 3772 (94.3%) completed the treatment. Of those eligible for sustained virologic response assessment, 71.0% (2641/3715) were evaluated, and the reported cure rate was 96.1% (2537). The study found the odds of patients starting HCV treatment differed by the type of facility they were screened at and whether they were registered as PWID at the screening sites. The patients screened at centers with integrated HCV treatment services had higher treatment uptake rates than those screened at other centers. ConclusionsAs the cumulative HCV treatment uptake and cure rates among MST patients with HCV infection are high (75.8% and 96.1%, respectively), the MST patients might become the first microelimination target population in which hepatitis C elimination will be achieved in Georgia. The study found the type of screening facility and whether MST patients registered themselves as PWID or not had significant effects on MST patients starting HCV treatment. At the same time, the study did not find gender and age to be significant predictors of MST patients starting HCV treatment. MST patients used different types of health facilities to get screened for HIV. Many of them did not register themselves as PWID when screened for HIV. The existence of only a few harm reduction sites with integrated HCV treatment services, a high level of stigma, and the criminalization of drug use might have incentivized MST patients to self-navigate across the HCV care continuum with the rest of the population. The implementation of focused, harm reduction, integrated HCV treatment with good peer and professional adherence support at treatment sites could help reach the hepatitis C elimination goals among MST patients.

Pretreatment Assessment of Psychosocial Readiness Is Not Associated with Improved Treatment Outcomes in a Safety-Net HCV Treatment Clinic.

Hepatitis C virus (HCV) is highly curable with antiviral therapy, and traditionally, treatment adherence has been critical for treatment success. We sought to determine whether assessing HCV treatment readiness with a structured treatment readiness tool was associated with increased rates of adherence and cure among patients at a safety-net HCV clinic. We administered the Psychosocial Readiness Evaluation and Preparation for HCV Treatment (PREP-C) tool to 50 patients and compared them with 50 patients who received the usual care. The outcome measures included achievement of treatment milestones (eg, adherence to treatment, clinic visit attendance) and sustained virologic response (cure). We found no association between receiving the PREP-C assessment and outcomes, including referral to or starting HCV treatment, adherence to treatment, and HCV cure. We found that receiving the PREP-C assessment did not improve treatment outcomes, suggesting that targeted pretreatment assessment is unnecessary even in a medically and psychosocially complex population.

2209. Discordance Between FibroSure and FibroScan Results in Hepatitis C and Human Immunodeficiency Virus Co-infected Patients Prior to Treatment for Hepatitis C Virus Infection

BackgroundThe accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognosis and treatment decisions. FibroSure and FibroScan are commonly used to approximate fibrosis prior to HCV treatment. Both methods have been validated for their correlation to the five-level (F0–F4) METAVIR scoring system. However, the correlation between these two tests in HIV/HCV co-infected patients has not been well described. Here, we evaluated the concordance between FibroSure and FibroScan-derived METAVIR results in HIV/HCV co-infected patients.MethodsWe performed a retrospective cross-sectional study of HIV/HCV co-infected patients that were treated between 2014 and 2017 at Drexel University, Philadelphia, PA. We described patient demographics and overall METAVIR scores of treated patients. Further, we compared the concordance between FibroSure and FibroScan results among patients who had both tests before the start of HCV treatment.ResultsOne hundred and thirty-eight HIV/HCV co-infected patients were treated. Most of them (N = 134, 97%) achieved sustained virologic response after 12 weeks of treatment. One hudred and thirty-three patients underwent FibroSure testing before starting HCV treatment. Of those, 62 (47%) fell in the F0–F2 range and 71 (53%) in the F3–F4 range. Of those 133 patients, 21 also underwent FibroScan. Fourteen (67%) fell in the F0–F2 range, while seven (33%) fell in the F3–F4 range. Of the 21 patients who both had FibroSure and FibroScan testing, 12 (57%) had concordant results, while nine (42%) had discrepant results. Of the patients with discrepant results, eight had higher fibrosis scores (F3–F4) with FibroSure, while only one had a higher fibrosis score (F3–F4) with FibroScan.ConclusionIn our study, more than half of HIV/HCV co-infected patients had advanced fibrosis score at the time of HCV treatment. When FibroSure and FibroScan scores were compared, close to half of co-infected patients had discordant results, the preponderance of which had higher FibroSure scores. As early initiation of HCV treatment is crucial to co-infected patients, further studies will need to evaluate the clinical significance of the discrepancy between different non-invasive fibrosis testing systems in co-infected patients.Disclosures All authors: No reported disclosures.

Hepatitis C cascade of care among people who inject drugs in Vancouver, Canada

Background: People who inject drugs (PWID) have high rates of hepatitis C virus (HCV) infection. Little is known about the rates of diagnosis and treatment for HCV among PWID. Therefore, this study aims to characterize the cascade of care in Vancouver, Canada, to improve HCV treatment access and delivery for PWID. Methods: Data were derived from 3 prospective cohort studies of PWID in Vancouver, Canada, between December 2005 and May 2015. The progression of participants was identified through 5 steps in the cascade of care: (1) chronic HCV; (2) linkage to HCV care; (3) liver disease assessment; (4) initiation of treatment; and (5) completion of treatment. Predictors of undergoing liver disease assessment for HCV treatment were identified using a multivariable extended Cox regression model. Results: Among 1571 participants with chronic HCV, 1359 (86.5%) had ever been linked to care, 1257 (80.0%) had undergone liver disease assessment, 163 (10.4%) had ever started HCV treatment, and 71 (4.5%) had ever completed treatment. In multivariable analyses, human immunodeficiency virus (HIV) seropositivity, use of methadone maintenance therapy, and hospitalization in the past 6 months were independently and positively associated with undergoing liver disease assessment (all P < .001), whereas daily heroin injection was independently and negatively associated with undergoing liver disease assessment (P < .001). Conclusions: Among this cohort of PWID, few had been started on or completed treatment for HCV. These findings highlight the need to improve the prescribing of HCV treatment among PWID with active substance use.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

To evaluate neutrophil gelatinase associated lipocalin (NGAL) in patients infected by hepatitis C virus (HCV) before and during treatment with directly acting antivirals (DAAs). NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate (eGFR). Then, NGAL and eGFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for non-parametric data. Differences in dichotomous variables were evaluated through χ (2) test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four (FIB-4), AST to platelet ratio index (APRI), and eGFR]. Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with eGFR < 60 mL/min vs patients with eGFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/dL were compared with those of NGAL ≤ 118.11 ng/dL, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis (P > 0.05). Linear correlation was found between NGAL and both age (P = 0.0475) and eGFR (P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for eGFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline (P = 0.0239). Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

Short Communication: CXCL12 rs1029153 Polymorphism Is Associated with the Sustained Virological Response in HIV/Hepatitis C Virus-Coinfected Patients on Hepatitis C Virus Therapy.

The immune response against HIV and hepatitis C virus (HCV) infection partly depends on chemokine-mediated recruitment of specific T cells. CXCL12 polymorphisms have been associated with AIDS progression and survival, but there are no data related to HCV infection. The aim of this study was to determine whether CXCL12 polymorphisms are related so as to achieve sustained virological response (SVR) after HCV therapy with pegylated-interferon-alpha/ribavirin (pegIFN-α/ribavirin) in HIV/HCV-coinfected patients. We carried out a retrospective study in 319 naive patients who started HCV treatment. The CXCL12 (rs266093, rs1029153, and rs1801157) and IL28B (rs12980275) polymorphisms were genotyped by using the GoldenGate assay. Genetic data were analyzed under an additive inheritance model. The overall rates of the SVR were 54.9% (175/319) and 41.5% (90/217) in GT1/4 patients and 83.2% (84/101) in GT2/3 patients. Patients with a favorable CXCL12 rs1029153 T allele had higher SVR rates than patients with the rs1029153 CC genotype (44% CC, 49% CT, and 61.3% TT; p = 0.025). No significant results for the rs266093 and rs1801157 polymorphisms were found. Patients harboring the favorable rs1029153 T allele had significantly increased odds of achieving SVR [adjusted odds ratio (aOR) = 1.55; 95% confidence interval (95% CI) = 1.01; 2.40; p = 0.047]. Moreover, no significant association was found when the study population was stratified by HCV genotype (data not shown), possibly due to the low number of patients in each group. In conclusion, in this study we found that the favorable CXCL12 rs1029153 T allele seems to be related so as to achieve an SVR in HIV/HCV-coinfected patients on pegIFN-α/ribavirin therapy.

Protease inhibitors to treat hepatitis C in the Swiss HIV Cohort Study: high efficacy but low treatment uptake.

Direct-acting antiviral agents (DAAs) have become the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. We aimed to assess treatment uptake and efficacy in routine clinical settings among HIV/HCV coinfected patients after the introduction of the first generation DAAs. Data on all Swiss HIV Cohort Study (SHCS) participants starting HCV protease inhibitor (PI) treatment between September 2011 and August 2013 were collected prospectively. The uptake and efficacy of HCV therapy were compared with those in the time period before the availability of PIs. Upon approval of PI treatment in Switzerland in September 2011, 516 SHCS participants had chronic HCV genotype 1 infection. Of these, 57 (11%) started HCV treatment during the following 2 years with either telaprevir, faldaprevir or boceprevir. Twenty-seven (47%) patients were treatment-naïve, nine (16%) were patients with relapse and 21 (37%) were partial or null responders. Twenty-nine (57%) had advanced fibrosis and 15 (29%) had cirrhosis. End-of-treatment virological response was 84% in treatment-naïve patients, 88% in patients with relapse and 62% in previous nonresponders. Sustained virological response was 78%, 86% and 40% in treatment-naïve patients, patients with relapse and nonresponders, respectively. Treatment uptake was similar before (3.8 per 100 patient-years) and after (6.1 per 100 patient-years) the introduction of PIs, while treatment efficacy increased considerably after the introduction of PIs. The introduction of PI-based HCV treatment in HIV/HCV-coinfected patients improved virological response rates, while treatment uptake remained low. Therefore, the introduction of PIs into the clinical routine was beneficial at the individual level, but had only a modest effect on the burden of HCV infection at the population level.

Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation.

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, ≥ moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.

Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected patients

BackgroundThe CXCL9, CXCL10 and CXCL11 (CXCL9–11) chemokines play a critical role in eradication of hepatitis C virus (HCV), although HCV-specific immunity often fails to eradicate the HCV, allowing the chronicity of hepatitis C. ObjectiveTo examine the association between CXCL9–11 polymorphisms and the sustained virological response (SVR) following hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin in HIV/HCV-coinfected patients. Study designWe performed a retrospective study in 176 naïve patients who started HCV treatment. The CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 polymorphisms were genotyped by GoldenGate® assay. Genetic data were analyzed under recessive inheritance model. The SVR was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment. ResultsIn the intention-to-treat analysis, the SVR rate was higher in HCV genotype 1/4 (GT1/4) patients carrying rs10336 TT (p=0.042), rs3921 GG (p=0.021), and rs4619915 AA (p=0.024) genotypes; and they had higher likelihood of achieving SVR (adjusted odds ratio (aOR)=3.26 (p=0.038), aOR=4.21 (p=0.019), and aOR=4.08 (p=0.022), respectively). For CXCL haplotype analysis (CXCL9/rs10336, CXCL10/rs3921, and CXCL11/rs4619915), the TGA haplotype (favorable alleles) had better odds of achieving SVR than the CCG haplotype (unfavorable alleles) in GT1/4patients (OR=2.69; p=0.003). No significant results were found in GT2/3 patients. Moreover, similar results were obtained in the on-treatment analysis. ConclusionsThe presence of homozygous for the minor allele of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 was related to higher likelihoods of achieving the HCV clearance after pegIFNα/ribavirin therapy in HIV infected patients coinfected with HCV GT1/4.

Variation between Canadian centres in the uptake of treatment for hepatitis C by patients coinfected with HIV: a prospective cohort study.

Uptake of treatment for hepatitis C virus (HCV) is low in Canada despite its publicly funded health care system. We explored the uptake of HCV treatment within the Canadian Co-infection Cohort to determine if some treatment centres have been more successful than others at starting patients with HIV-HCV coinfection on HCV treatment. We estimated the variation between 16 centres in the uptake of HCV treatment using a Weibull time-to-event model with adjustment for patient characteristics that are thought likely to influence the uptake of treatment. We asked the principal investigator at each centre about access to hepatitis-related specialists and services and the importance of various criteria when determining if a patient with HIV-HCV coinfection should receive treatment for HCV. Among 681 untreated patients in the Canadian Co-infection Cohort, 163 patients with HIV-HCV coinfection started HCV treatment over a period of 1827 patient-years (9 per 100 patient-years). Even after adjustment for case mix, there was still appreciable variation in treatment uptake between centres, with mean hazard ratios of 0.43 (95% credible interval 0.11-1.3) and 3.6 (95% credible interval 1.7-8.4) for the centres least and most likely to start an average patient with HIV-HCV coinfection on HCV treatment. The most important criteria reported by principal investigators for determining eligibility for treatment were severity of fibrosis, current psychiatric comorbidities, current alcohol intake, past HCV treatment and a history of reinfection with HCV. However, the opinions were wide-ranging: 8 of the 15 criteria elicited both the responses "less important" and "very important." The magnitude of the centre effects and diverse opinions about the importance of treatment eligibility criteria suggest that provider-related barriers to HCV treatment uptake are as important as patient-related barriers.

IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus‐/HCV‐coinfected patients

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035G allele remained independently associated with early failure in the overall population (OR=4.15 (95% CI=1.64-10.54) and OR=2.00 (95% CI=1.19-3.36), respectively) as well as in GT1/4 patients (OR=5.07 (95% CI=1.81-14.22) and OR=2.03 (95% CI=1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802±0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.

Ribavirin and abacavir drug interaction in HIV–HCV coinfected patients

To examine the impact of ribavirin and abacavir coadministration on hepatitis C virus (HCV) virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. Pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. Patients receiving ribavirin-pegylated interferon for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) as well as HCV-RNA decline were evaluated. Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (interquartile range) ribavirin Cmin was 1.6 mg/l (1.2-2.2) with no statistical difference between abacavir users and nonusers [1.5 mg/l (0.99-2.1) and 1.7 (1.2-2.3), P = 0.15]. RVR and EVR were 52 and 72%, respectively. There was no difference observed in the proportion of abacavir users vs. nonusers achieving RVR (respectively 59 vs. 50%, P = 0.40) or EVR (72 vs. 73%, P = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log(10) IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) P = 0.28] or at week 12 [-1.76 log(10) IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (P = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir nonusers, but the difference was not statistically significant (P = 0.059). In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and nonusers, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is, therefore, a well tolerated treatment alternative for coinfected patients starting HCV treatment.