Hepatitis C Virus Mono-infected Patients Research Articles

Outcome of direct-acting antiviral treatment in patients with hepatitis C virus/hepatitis B virus coinfection

BackgroundOral direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection have greatly improved treatment efficacy, with sustained virological response (SVR) rates of > 95% for HCV monoinfected patients. However, hepatitis B virus (HBV)/HCV coinfection is more complex than monoinfection with HBV or HCV alone. We evaluated the SVR rate at 12 weeks post-treatment with DAAs in patients with HCV/HBV and evaluated the rate of HBV reactivation during and 6 months after treatment.ResultsAmong the included patients, 191 (95.5%) achieved SVR. Older age, low platelet count, high serum creatinine, and higher liver stiffness value measured by fibroscan were predictors of failure to achieve SVR. The 16 patients (8%) with HBV reactivation patients had significantly higher ALT and serum creatinine and a high HCV RNA viral load at baseline compared with that of those without HBV reactivation.ConclusionPatients who received DAAs to treat HCV/HBV coinfection showed a high SVR. However, it is important to be aware of the potential risk for HBV reactivation during and after treatment with DAAs.

THU-195 - Long term normalization of systemic inflammation and endothelial activation after hepatitis C virus (HCV) eradication in HIV/HCV coinfected, HCV monoinfected patients and HCV-infected liver transplant recipients

THU-195 - Long term normalization of systemic inflammation and endothelial activation after hepatitis C virus (HCV) eradication in HIV/HCV coinfected, HCV monoinfected patients and HCV-infected liver transplant recipients

Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients.

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n=695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n=7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy.

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.

Late presentation for HCV care: Time to target people with diabetes and/or hazardous alcohol use (ANRS CO22 HEPATHER cohort).

Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals. This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome. Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care. As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030.

Long-term outcome of liver complications in patients with chronic HBV/HCV co-infection after antiviral therapy: a real-world nationwide study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44years. Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65year-old, BMI ≥ 27kg/m2, FIB-4 ≥ 3.25, eGFR < 60ml/min/1.73m2, and non-HCV SVR, but not HBV co-infection. Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

Changes in Serum Interferon Gamma and Interleukin-10 in Relation to Direct-Acting Antiviral Therapy of Chronic Hepatitis C Genotype 4: A Pilot Study

This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers. This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay. All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers. Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

Innate immune response in Plasmodium coinfection with HBV and HCV using complement C3, C4, and CD4+ T cells

Study backgroundComplement, CD4+ T cells, and antibodies are immune materials for protection or are expressed for the detection of pathogens. Complements are activated by the classical or alternative pathway complement to cause cell death.Aim and objectiveThis study was designed to evaluate the innate immune response in Plasmodium coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) using complement C3, C4, and CD4+ T cells to provide information for useful directions in the management of malaria and hepatitis B and C.Materials and methodsThe participants recruited for this study include controls who were neither infected with Plasmodium nor hepatitis B and C (n = 50) and Plasmodium-infected participants (n = 50) and hepatitis C-infected participants (n = 30) and hepatitis B-infected participants (n = 30) and Plasmodium coinfected with hepatitis B participants (n = 30) and Plasmodium coinfected with hepatitis C participants (n = 30) aged 19–65 years. Complement C3, C4, CD4+ T cells HCV and HBV were determined in each of the participant by enzyme-linked immunosorbent assay method. Identification of Plasmodium was carried out using the thick and thin film technique using Giemsa and Leishman staining, while test and controls with elevated and normal total bile acids, respectively, were negative to HIV and acid fast bacilli tests were included.ResultsThe results obtained in this study showed a significant decrease in plasma complement C3 in patients with monoinfection of Plasmodium, HCV, HBV, and Plasmodium patients coinfected with HCV and HBV compared with the control (P < 0.005). There was also a significant decrease in plasma complement C4 in Plasmodium patients coinfected with HCV and HBV compared with the control (P < 0.005). The results obtained in Plasmodium patients coinfected with HBV and HCV, and HBV patients coinfected with HCV showed a significant decrease in CD4+ T cells compared with the results obtained in the control (P < 0.005). There was significantly lower plasma complements C3, C4, and blood CD4+ T cells in Plasmodium monoinfected patients than in HBV or HCV monoinfected patients (P < 0.005). There was also a significantly lower plasma complement C4 and CD4+ T cells in Plasmodium patients coinfected with HBV or HCV than patients who were monoinfected with HCV and HBV (P < 0.005).ConclusionThere was significant alterations in the blood complement C3, C4, and CD4+ T cells in response to Plasmodium, HBV, HCV mono- and coinfection which was more influenced by Plasmodium infection.

Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt

Background: Hepatitis C virus (HCV) is highly distributed in Egypt. Moreover, parasitic diseases such as schistosomiasis, toxoplasmosis, or amebiasis are frequent in Egypt. Dual infections of HCV and each of these parasitic diseases are possible and associated with bad clinical consequences. The present study was done to monitor the clinical, biochemical, and hematological changes in Toxoplasma gondii, Entamoeba histolytica, and/or Schistosoma co-infection in the HCV-infected patients from Menoufia Province, Egypt. Methods: One hundred and nine blood samples, HCV monoinfected patients and co-infected with T. gondii, E. histolytica, and/or Schistosoma, were monitored and subjected to clinical chemistry and hematological examinations Results: Liver cirrhosis in patients with concomitant multiple parasites during chronic HCV infections showed a high percentage compared to HCV mono-infected patients. Moreover, significant increases in the level of alpha-fetoprotein, aspartate transaminase, prothrombin time, and the relative monocyte count were demonstrated in patients with concomitant multiple parasites during chronic HCV infections compared to HCV mono-infected patients. Changes in the levels of platelets and relative lymphocytes/neutrophils count were detected during dual or multiple infections. Conclusions: Schistosomiasis, toxoplasmosis, or amebiasis had unpropitious effects on HCV-infected patients and it is recommended to screen these parasitic diseases among HCV patients to reduce the HCV clinical outcome.

HIPPOCRATES® project: A proof of concept of a collaborative program for hepatitis C virus micro-elimination in a prison setting.

BACKGROUNDIn the last few years we have witnessed a revolution in the treatment of hepatitis C virus (HCV) infection. With the introduction of direct-acting antiviral agents (DAAs), sustained virological response (SVR) is achieved in more than 95% of the patients. The focus is now being turned to the global targets set by the World Health Organization, with the aim of achieving HCV elimination by 2030. Prison inmates constitute one of the high-risk groups, and receive treatment less frequently due to several barriers in access to health care.AIMTo describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting, where tertial referral liver center specialists locally provide, on-site assessment and treatment for the prisoners.METHODSA prospective observational study was conducted from April 2017 to March 2020, which included all HCV monoinfected prison inmates in the largest Northern Portugal prison. Demographic, clinical, and laboratory data, as well as transient elastography measurements, were collected onsite by the medical team and prospectively recorded. Patients were treated with DAA according to international guidelines. The primary endpoint was SVR at post-treatment week 12. RESULTSThere were 98 monoinfected HCV male inmates (mean age, 42.7 ± 8.6 years) included in the analysis. Injecting drugs or tattooing were reported in 74.5%, with 38.8% of the latter being done in prison. Alcohol consumption of more than 30 g/d was referred in 69.4%. The most prevalent genotype was 1a (54.1%), followed by 3 (27.6%), 4 (9.2%) and 1b (6.1%). Pretreatment fibrosis degree was mild-to-moderate (F0-F2) in 77.6% and severe in 22.4% (F3-F4). Treatment regimens chosen were: 45.9% elbasvir/grazoprevir, 29.6% sofosbuvir/velpatasvir, and 12.2% sofosbuvir/ledispavir and glecaprevir/pibrentasvir. No major adverse events were observed. SVR at post-treatment week 12 was 99%.CONCLUSIONIn a population considered to be both hard-to-access and a cornerstone for HCV elimination, the onsite evaluation and treatment of HCV-infected prisoners, achieved an exceptional highly effective success rate. This type of collaborative program should be considered to be expanded, to support hepatitis C elimination efforts.

Hepatitis delta virus propagation enabled by hepatitis C virus-Scientifically intriguing, but is it relevant to clinical practice?

In vitro cell culture experiments and animal models have demonstrated that hepatitis delta virus (HDV) can theoretically propagate being enveloped by human pathogenic viruses other than hepatitis B virus (HBV), namely hepatitis C virus (HCV) and dengue virus. However, the clinical relevance of these findings and whether HDV replication occurs in real-world hepatitis B surface antigen (HBsAg)-negative HCV patient cohorts remain unknown. To this aim, we analysed 323 HCV-RNA-positive and HBsAg-negative sera for the presence of HDV-RNA and anti-HDV antibodies (anti-HDV). All 323 (100%) samples were negative for HDV-RNA. Interestingly, 8/316 samples tested positive for anti-HDV. The HBV serology of these eight patients showed a positive result for HBV core antibodies (anti-HBc) indicating a seroconversion of an acute HBV infection in the past. None of the anti-HBc-negative patients were positive for anti-HDV. Our results indicate a distinctly low probability of replicative HDV infection in HCV mono-infected patients in Germany. Current German clinical guidelines rightly recommend performing HDV screening only in HBsAg-positive patients. However, larger studies on this subject should be performed in regions that are endemic for chronic HBV/HDV as well as HCV infections.

Sustained Virologic Response Rates of Direct Acting Antivirals in HIV Coinfected Hepatitis C Patients and Its Effect on Liver Fibrosis

Background: Hepatitis C virus (HCV) is an important cause of chronic hepatitis with necroinflammation and fibrosis resulting in end stage liver disease and hepatocellular carcinoma. Direct acting antivirals (DAAs) are newer agents that directly interfere with the HCV lifecycle and result in high rates of sustained virologic response (SVR). We evaluated if treatment with DAAs in a real-world setting is as successful in HCV/HIV coinfected patients as it is in HCV monoinfected patients, and if some degree of fibrosis regression can be observed after completion of therapy in both groups. Methods: We retrospectively reviewed data from HCV monoinfected and HCV/HIV coinfected patients who received treatment from 2014-2016 at the East Carolina University Infectious Diseases clinic. The primary outcome was to compare completion and sustained virologic response (SVR) rate at either 12 or 24 weeks between HCV monoinfected patients and HCV/HIV coinfected patients. The secondary outcome was to assess regression of fibrosis at either 12 or 24 weeks after completion of therapy, defined as one METAVIR stage improvement in their FibroSure™, a noninvasive biochemical test to estimate the stage of fibrosis. Results: There were 41 patients in each group. Compared to the coinfected group, patient no show rate was higher in the monoinfected group (p=0.0346). In the HCV monoinfected group, 25 (93%) achieved either SVR 12 or 24. Two patients were non-compliant and had detectable viral load on evaluation at week 12. In the HCV/HIV coinfected group, 37 patients achieved SVR (p=0.0039). One patient in the coinfected group did not complete therapy but achieved SVR. In terms of fibrosis, 12/18 (67%) in the monoinfected group demonstrated improvement in at least 1 Metavir stage and 6/18 (33%) had no change. In the coinfected group, 8/16 (50%) patients demonstrated an improvement in FibroSure™ stage, 5/16 (31%) had no change, and 3/16 (19%) had worsening fibrosis according to FibroSure™ stage, (p=0.4867). Conclusions: In this small, real-world cohort, HCV/HIV coinfected patients treated with DAAs had higher completion and SVR rates than HCV monoinfected patients. Treatment failures in the monoinfected group were all linked to non-adherence, whereas, more coinfected patients achieved SVR, likely related to the fact that they were regularly engaged in routine HIV care. Fibrosis regression based on FibroSure™ was observed more in monoinfected patients than those with coinfection. Although not statistically significant, at least 50% of the patients in each group had regression of fibrosis.

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

BackgroundLiver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated.MethodsPatients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis.Results93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6–44.6) and 24.6 (range 6.8–47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04–1.13), male sex (HR = 2.76; 95% CI 1.28–5.96), lower albumin levels (HR = 3.94; 95% CI 1.81–8.58), genotype 3 (HR = 5.05; 95% CI 1.75–14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01–3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00–1.07), male sex (HR = 2.13; 95% CI 1.06–4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89–7.46) were independently associated with the appearance of a decompensating event after viral eradication.ConclusionDifferent demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.

Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients.

In human immunodeficiency virus (HIV) and hepatitisC virus (HCV) coinfected patients, the progression of liver failure is reported to be more aggressive than that in HCV mono-infected patients. Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+ -M2BP) is well recognized as a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We analyzed HIV/HCV coinfected patients' M2BP levels as a possible marker for predicting liver fibrosis. M2BP was measured in 31 HIV/HCV coinfected patients, and we analyzed the correlation between WFA+ -M2BP and several markers of fibrosis, liver function, and tumor markers. We compared the WFA+ -M2BP levels in HIV/HCV coinfected patients with those of HCV mono-infected patients by performing a propensity score matching analysis. In the HIV/HCV coinfected patients, the serum level of WFA+ -M2BP was well correlated with the markers typeIV collagen, hyaluronic acid, and alpha-fetoprotein, but not protein induced by vitamin K absence-II. In the propensity score matching with HCV mono-infected patients, the WFA+ -M2BP levels were significantly higher in the HIV/HCV coinfected patients compared with the levels in the HCV mono-infected patients. In conclusion, WFA+ -M2BP might be a feasible predictive marker of fibrosis in HIV/HCV coinfected patients.

The HIPPOCRATES Project: A Proof of Concept Promoting HCV Microelimination Strategy Plan in Prisons

Background & Aims: In the last few years we have witnessed a revolution in the treatment of hepatitis C virus (HCV) infection. With the introduction of direct-acting antiviral agents (DAA), sustained virological response (SVR) is achieved in more than 95% of the patients. The focus is now being turned on to high-risk groups, with the aim of achieving HCV elimination by 2030. Prison inmates constitute one of the high-risk groups, and they receive treatment less frequently due to barriers in access to health care. The aim of this study is to describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting. Methods: A prospective observational study was performed including all prison inmates monoinfected with HCV, from April 2017 to March 2018 in a Portuguese prison. Demographic, clinical and laboratorial data, as well as transient elastography measurements, were collected onsite by the medical team and prospectively recorded. Patients were treated with DAA according to international guidelines. SVR rates and adverse events were analyzed. Results: 67 monoinfected HCV male inmates (mean age of 42,4 ±8,1 years) were enrolled. 72% reported history of injecting drugs or tattooing, with 44% of the latter being made in prison. 78% referred alcohol consumption of more than 30 g/day. The most prevalent genotype was 1a (54%), followed by 3 (30%) 4 (9%) and 1b (8%). Pretreatment fibrosis degree was mild-to-moderate (F0-F2) in 78% and severe in 22% (F3-F4). Treatment regimens chosen were: 52% elbasvir/grazoprevir, 30% sofosbuvir/velpatasvir and 18% sofosbuvir/ledispavir. No major adverse events were observed. SVR rate was 100%. Conclusions: In a population considered hard-to-access and a cornerstone for HCV elimination, the doctors' visits to the prison setting, as well as the assisted medication administration lead to a 100% rate of SVR. Funding Statement: The authors declare: None. Declaration of Interests: The authors declare: None. Ethics Approval Statement: This study was conducted according to the Declaration of Helsinki. The ethical approval for this study was obtained from the Ethics Committee of Centro Hospitalar Sao Joao and Porto's correctional system. Informed consent was obtained from each patient before each treatment.

1965. Safety and Efficacy of Glecaprevir/Pibrentasvir in Patients With Chronic Hepatitis C Virus Genotypes 1–6 and Human Immunodeficiency Virus-1 Co-Infection: An Integrated Analysis of Two Phase 3 Clinical Trials

BackgroundPeople co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 may be treated for HCV without special considerations apart from drug interactions with antiretroviral therapies (ART). The once-daily, all-oral, ribavirin-free, pangenotypic combination of glecaprevir (identified by AbbVie and Enanta) and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in HCV mono-infected patients. We evaluated the safety/efficacy of glecaprevir/pibrentasvir in patients co-infected with HCV/HIV-1.MethodsData were pooled from two Phase 3 trials for treatment-naïve and -experienced patients co-infected with HCV genotypes (GT) 1–6/HIV-1 without cirrhosis or with compensated cirrhosis who received glecaprevir/pibrentasvir for 8 or 12 weeks. Virologic response, adverse events (AEs), and laboratory abnormalities were evaluated.ResultsAcross the two trials, 152 patients without cirrhosis and 16 with compensated cirrhosis received glecaprevir/pibrentasvir for 8 and 12 weeks, respectively. Baseline demographics are shown in Tables 1 and 2. The overall intention-to-treat (ITT) SVR12 rate was 98.2% (165/168), with no virologic failures among non-cirrhotic patients treated for 8 weeks; mITT rate (excluding non-virologic failures) was 99.4% (167/168). Reasons for nonresponse were breakthrough (n = 1; patient with incomplete study drug adherence), premature study drug discontinuation (n = 1), and missing SVR12 data (n = 1). Safety analyses included the additional 18 non-cirrhotic GT1-infected patients treated for 12 weeks (all achieved SVR12). AEs occurring in ≥5% of patients were fatigue, headache, nausea, and nasopharyngitis. Serious AEs and AEs leading to discontinuation were rare; none were related to study drug. Grade 3 or higher laboratory abnormalities were infrequent. All patients maintained HIV-1 suppression (<200 copies/mL) during treatment.ConclusionGlecaprevir/pibrentasvir was highly efficacious and well tolerated in patients co-infected with HCV GT1–6/HIV-1 without or with cirrhosis following 8 or 12 weeks of treatment, respectively, and could be the first 8-week pangenotypic treatment option for HCV/HIV-1 co-infected patients without cirrhosis. Disclosures J. K. Rockstroh, Gilead, Abbott, AbbVie, BMS, Bionor, Cipla, Janssen, Merck, ViiV: Consultant, Grant Investigator, Research Contractor and Scientific Advisor, Consulting fee, Research grant, Research support and Speaker honorarium. S. R. Bhagani, AbbVie, BMS, Gilead, Janssen, Merck, ViiV: Board Member, Consultant, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. R. Soto-Malave, AbbVie, Janssen, Merck: Consultant, Grant Investigator, Research Contractor and Scientific Advisor, Consulting fee, Research grant and Research support. K. Lacombe, AbbVie, BMS, Gilead, Janssen, Merck: Board Member, Consultant and Scientific Advisor, Consulting fee and Speaker honorarium. Z. Zhang, AbbVie Inc.: Employee and Shareholder, Salary and Stock and/or options. S. Wang, AbbVie Inc.: Employee and Shareholder, Salary and Stock and/or options. F. Mensa, AbbVie Inc.: Employee and Shareholder, Salary and Stock and/or options. R. Trinh, AbbVie Inc.: Employee and Shareholder, Salary and Stock and/or options.

Are there any challenges left in hepatitis C virus therapy of HIV-infected patients?

Direct-acting antivirals (DAAs) have tremendously improved the treatment of hepatitis C virus (HCV) infections also in human immunodeficiency virus (HIV)-positive individuals. Curing HCV infection is of particular importance in HIV-positive individuals as liver disease progression is accelerated in the course of concomitant HIV infection. Former challenges, such as safety and tolerability as well as reduced treatment uptake of pegylated interferon and ribavirin-based treatments, have been overcome with the approval of DAAs. Indeed, rates of discontinuation under modern all-oral DAA therapy in HIV/HCV coinfection have been reported to be <1%. Rates of sustained virological response (SVR) following treatment have aligned with those seen in HCV monoinfected patients, resulting in an equalisation of treatment recommendations for HCV monoinfected and HIV/HCV coinfected patients. Nevertheless, coinfection with HIV has been associated with slightly higher relapse rates in some real-world cohorts, arousing discussion regarding more individualised treatment once again. Moreover, an ongoing epidemic of acute HCV infections in HIV-positive men who have sex with men with high re-infection rates challenges physicians and researchers. The present review gives a concise summary of the remaining challenges in HCV treatment of HIV-positive individuals.

Meeting the Challenge: Hepatitis C Virus and HIV Care Experiences Among HIV Specialty Providers.

Hepatitis C virus (HCV) is frequently comorbid with HIV infection and is independently associated with a significant increase in all-cause mortality among HIV-positive adults. HIV specialists' role and experiences in treating HCV has been understudied, especially among those providers who actively treat patients with HCV. We conducted a brief online survey of HIV specialists (physicians, nurse practitioners, physician assistants, and prescribing pharmacists) who treat patients with HCV to examine their experiences with treating these patients (HCV monoinfected, HIV/HCV coinfected). Survey questions assessed providers' annual caseloads, barriers, and facilitators to providing HCV care, likelihood of providing HCV treatment to patients with various risk factors, and the extent to which their HCV screening practices aligned with CDC (Centers for Disease Control) guidelines for patients from various risk groups. A total of 168 HIV care providers were included in analyses. Nearly all specialists surveyed actively treated HIV/HCV coinfected patients, while fewer treated any HCV monoinfected patients. Providers' screening practices typically aligned with guidelines across patient groups, but their likelihood of prescribing HCV treatment to patients varied across patients' risk profiles. Providers endorsed high levels of knowledge to treat HCV-infected patients, but highlighted key barriers to providing optimal care. Given that HIV specialists are an active group treating patients with HCV, they may benefit from specialized guidance on managing HCV in patients with complex histories, including comorbid HIV infection.

Timing of treatment initiation of direct-acting antivirals for HIV/HCV coinfected and HCV monoinfected patients

ABSTRACTDirect-acting antiviral therapy is safe and cost-effective for the treatment of hepatitis C virus (HCV) infection. However, variability in drug payment rules represents a barrier to treatment that may disproportionately affect certain populations. We conducted a retrospective cohort study among HIV/HCV coinfected and HCV monoinfected patients using Kaplan–Meier and Fisher’s exact test to analyze the time from the prescription of a direct-acting antiviral agent to delivery to the patient. Variables with significance p < .20 in univariate analysis were included in a Cox regression model. Factors associated with faster treatment were Infectious Diseases office setting (p = .01), public insurance payer (p = .01), and initial approval of requested regimen (p = .01). The presence of other liver disease was associated with delay in treatment (p = .05). Unrestrictive Medicare and Medicaid regulations resulted in more rapid delivery of medication compared to private payers. Fibrosis level, Child–Pugh class and HIV status did not significantly change time to treatment.

Proteomic fingerprinting in HIV/HCV co-infection reveals serum biomarkers for the diagnosis of fibrosis staging.

BackgroundHepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS).MethodsSera from 83 HIV/HCV co- and 68 HCV mono-infected subjects in 4 stages of fibrosis were tested. Sera were fractionated, randomly applied to protein chip arrays (IMAC, CM10 and H50) and spectra were generated at low and high laser intensities.ResultsSixteen biomarkers achieved a p value < 0.01 (ROC values > 0.75 or < 0.25) predictive of fibrosis status in co-infected individuals and 14 in mono infected subjects. Five of these candidate biomarkers contributed to both mono- and co-infected subjects. Candidate diagnostic algorithms were created to distinguish between non-fibrotic and fibrotic individuals using a panel of 4 biomarker peaks.ConclusionThese data suggest that SELDI MS profiling can identify diagnostic serum biomarkers for fibrosis that are both common and distinct in HIV/HCV co-infected and HCV mono-infected individuals.