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Various immune checkpoint proteins have been linked to cirrhosis. This study aimed to explore the association between plasma levels of these proteins measured one year after successful HCV treatment and persistently liver stiffness (defined as liver stiffness measurement (LSM) ≥ 12.5 kPa) five years after HCV treatment in people with HIV (PWH). We conducted a retrospective study involving 39 patients with HIV/HCV-coinfection who had advanced fibrosis or cirrhosis and achieved sustained virologic response (SVR). Plasma samples were obtained one year after treatment, and levels of immune checkpoints along with inflammatory biomarkers were evaluated using a Luminex 200TM analyzer. Statistical analyses were performed using Generalized Linear Models (GLMs) with a gamma distribution. Spearman correlation tests were used to analyze the correlation between significant immune checkpoints and inflammatory biomarkers. Although LSM values showed a decreasing trend over the years following successful HCV treatment, this trend was not statistically significant due to substantial variability among PWH. Persistently high liver stiffness was observed in 61.5% of patients five years after HCV treatment. Elevated plasma levels of soluble BTLA, PD-1, and TIM-3 one year after HCV treatment were associated with persistently liver stiffness five years later. These significant immune checkpoints were found to correlate with inflammatory biomarkers in PWH with persistently high liver stiffness. In conclusion, increased plasma concentrations of immune checkpoints one year after successful HCV therapy were linked to persistently high liver stiffness five years later, particularly BTLA, PD-1, and TIM-3. This suggests a potential immunopathological mechanism in ongoing liver stiffness post-HCV eradication. [ABSTRACT FROM AUTHOR]

Background: Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection. Methods: We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. Results: During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. Conclusion: We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment. [ABSTRACT FROM AUTHOR]

Various immune checkpoint proteins have been linked to cirrhosis. This study aimed to explore the association between plasma levels of these proteins measured one year after successful HCV treatment and persistently liver stiffness (defined as liver stiffness measurement (LSM) ≥ 12.5 kPa) five years after HCV treatment in people with HIV (PWH). We conducted a retrospective study involving 39 patients with HIV/HCV-coinfection who had advanced fibrosis or cirrhosis and achieved sustained virologic response (SVR). Plasma samples were obtained one year after treatment, and levels of immune checkpoints along with inflammatory biomarkers were evaluated using a Luminex 200TM analyzer. Statistical analyses were performed using Generalized Linear Models (GLMs) with a gamma distribution. Spearman correlation tests were used to analyze the correlation between significant immune checkpoints and inflammatory biomarkers. Although LSM values showed a decreasing trend over the years following successful HCV treatment, this trend was not statistically significant due to substantial variability among PWH. Persistently high liver stiffness was observed in 61.5% of patients five years after HCV treatment. Elevated plasma levels of soluble BTLA, PD-1, and TIM-3 one year after HCV treatment were associated with persistently liver stiffness five years later. These significant immune checkpoints were found to correlate with inflammatory biomarkers in PWH with persistently high liver stiffness. In conclusion, increased plasma concentrations of immune checkpoints one year after successful HCV therapy were linked to persistently high liver stiffness five years later, particularly BTLA, PD-1, and TIM-3. This suggests a potential immunopathological mechanism in ongoing liver stiffness post-HCV eradication.

BackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection.MethodsWe performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.ResultsDuring follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.ConclusionWe discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

Background The Swiss HCVree Trial (NCT 02785666) was conducted in 2015–2017 with the goal of implementing a population-based systematic hepatitis C virus (HCV) micro-elimination program among men who have sex with men (MSM) with human immunodeficiency virus (HIV) enrolled in the Swiss HIV Cohort Study (SHCS). The trial led to a 91% and 77% decline of HCV prevalence and incidence, respectively. The long-term effect of this HCV micro-elimination program is yet to be explored. Methods All MSM enrolled in the SHCS were screened for HCV RNA using stored plasma samples obtained in 2019, termed "Swiss HCVree Post" screen. The incidence of HCV infection over time was assessed using additional information on HCV testing routinely collected in the SHCS. Characteristics of participants with replicating HCV infection were analyzed. Results The point-prevalence of "Swiss HCVree Post" (N = 4641) was 0.6%, reflecting a decline of 48% compared to the end of the Swiss HCVree Trial where the prevalence was 1.2%. Further, the incidence of HCV among MSM in the SHCS declined from 0.31/100 person-years (py) (95% confidence interval [CI] [.17,.55]) in 2017 to 0.19/100 py (95% CI [.09,.39]) in 2019. Conclusions A systematic HCV RNA-based screening among MSM with HIV conducted 2 years after the Swiss HCVree Trial revealed a sustained effect and further decline of the prevalence and incidence of replicating HCV infection. This indicates that the Swiss HCVree Trial was successful in curbing the HCV epidemic among MSM with HIV in Switzerland. Clinical Trials Registration NCT02785666. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). Methods Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. Results In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1–Q3) follow-up time of 43 (31–49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P =.013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]:.08–.90; P =.034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5–24.9; P <.001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01–1.86; P =.043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01–1.06, for 1 kPa increase; P =.011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI:.11–.85). Conclusions Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated. [ABSTRACT FROM AUTHOR]

Approximately 25% of HIV-infected patients are co-infected with HCV. Notably, the burden of HCV infection (e.g., viral persistence, viral load, or HCV-related liver symptoms) is more pronounced in the presence of HIV co-infection. However, to date, the underlying immune mechanisms accounting for accelerated disease progression in HIV/HCV-coinfected individuals have not been described in sufficient detail. We hypothesized that regulatory T cells (Treg) bearing potent immunosuppressive capacities could not only play a substantial role in the pathogenesis of HCV/HIV coinfection but also modulate the response to the standard anti-viral therapy. Materials and Methods: To this end, we studied alterations in frequencies of Treg cells in correlation with other Treg-related and virus-related parameters in both HCV and HCV/HIV-infected patients subjected to standard pegIFN-α/RBV therapy. Results: Notably, we found that pegIFN-α/RBV therapy significantly increased levels of Treg cells in HCV-infected but not in HIV/HCV-coinfected individuals. Furthermore, HIV/HCV-coinfection was demonstrated to inhibit expansion of regulatory T cells during anti-viral treatment; thus, it might probably be responsible for viral persistence and HCV-related liver damage. Conclusions: Therapy with pegIFN-α/RBV demonstrated a significant effect on regulatory T cells in the course of HIV and/or HCV infection indicating a crucial role in the anti-viral immune response.

Abstract. The role of hepatitis C virus (HCV) co-infection in violation of restoring CD4+T cells in HIVinfected patients receiving antiretroviral therapy (ART) was investigated. Seventy eight patients with effective virological response to ART (viral load < 50 copies/ml) who either had or had no good immunological CD4+Tcell response after two years of treatment were recruited. Twenty one relatively healthy volunteers served as controls. The numbers of main T-lymphocyte populations and their apoptosis rates were determined. Thymus productive function was assessed by the number of αTREC-positive CD4+ and CD8+T cells. It is shown that HIV/HCV co-infection is characterized by lower numbers of CD4+T-lymphocytes in patients’ blood compared with HIV-monoinfection. This is not associated with the cells’ increased death rates. We also demonstrate that HCV coinfection reduces the production of CD4+, but not CD8+T-lymphocytes, by the thymus.

Background As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. Objectives and Study design Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). Results Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus ≥800,000 IU/mL (OR 4.403, 95% CI 1.29–15.04; p = 0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07–10.48; p = 0.038). Conclusions Overall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000 IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis A (HAV) and B (HBV) vaccination is strongly recommended for HIV-infected patients, especially those with hepatitis C coinfection. The aim of this study was to determine the prevalence of antibodies directed against HAV and HBV in a large cohort of HIV/HCV-coinfected patients, and to identify factors associated with HAV and HBV vaccination. Patients and methods: We studied 1175 HIV/HCV-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort, whose HAV and HBV serostatus was known. Results: 1056 patients (89.9%) have been tested for anti-HBc IgG, anti-HBs, and HbsAg. Only 10.9% of patients had received HBV vaccination and 70% of the patients with no HBV immunity (231/265) had never received HBV vaccination. In multivariate analysis, male sex (OR 2.0. 95% CI 1.1–3.8; p =0.02), a higher level of school education (OR 2.5, 95% CI 1.3–4.5; p =0.003), a higher CD4 cell nadir (OR 1.05, 95% CI 1.009–1.103; p =0.018) and no cirrhosis (OR 2.7, 95% CI 1.2–6.4; p =0.02) were associated with HBV vaccination. Only 368 patients (31.3%) were tested for immunity to HAV. Despite a frequent lack of HAV immunity (48.3%), a low rate of HAV vaccination (6%) was observed. In multivariate analysis, a higher level of school education (OR 3.6, 95% CI 1.03–12.4; p =0.045) was the only factor associated with HAV vaccination. HAV screening rates and HAV and HBV vaccination rates were low in this population of HIV/HCV-coinfected patients. The benefits of routine HAV and HBV screening, vaccination and post-vaccination testing should be emphasized. [Copyright &y& Elsevier]

Summary: Objectives: HIV-coinfection accelerates the course of HCV-related liver disease. Since, highly active anti-retroviral therapy significantly improved survival of HIV-patients more coinfected patients develop end stage liver disease. Therefore, treatment options for chronic hepatitis C in HIV-coinfected patients need to be evaluated. Methods: Efficacy and safety of pegylated interferon α-2b (peg IFN) plus ribavirin (RBV) was examined within this prospective, uncontrolled, multicentre trial. Patients received peg IFN (1.5μg/kg) once weekly plus RBV 800mg daily for 48 weeks for HCV genotypes (GT) 1/4 and 24 weeks for GT 2/3. Results: One hundred and twenty-two patients were enrolled. Patients were predominantly male (68%) and former i.v. drug users (61%). Baseline characteristics (median) were as follows: age 39 years (range 23–58), CD4 count 494cells/μl (range 150–1578/μl), HIV-RNA 2.3log copies/ml (range <1.7–5.4log copies/ml). 61% currently received anti-retroviral treatment. Fifty-six percent had HCV GT 1. EOT response was achieved by 52%. However, only 25% achieved sustained response (SR) due to a high relapse rate. SR rates were significantly higher among patients with GT 2/3 compared to those with GT 1/4 (44 vs. 18%). SR was observed in only one patient without early response (ER). Discontinuation rate was 30%, 21% discontinued due to adverse events. Conclusion: Peg IFN/RBV appears safe and effective in HIV/HCV-coinfected patients. GT 2/3 is associated with better SR. Lack of ER strongly predicts non-response. High relapse rates substantially reduce treatment success. In terms of toxicity neuro-psychiatric side effects frequently required treatment discontinuation. [Copyright &y& Elsevier]

Approximately 25% of HIV-infected patients are co-infected with HCV. Notably, the burden of HCV infection (e.g., viral persistence, viral load, or HCV-related liver symptoms) is more pronounced in the presence of HIV co-infection. However, to date, the underlying immune mechanisms accounting for accelerated disease progression in HIV/HCV-coinfected individuals have not been described in sufficient detail. We hypothesized that regulatory T cells (Treg) bearing potent immunosuppressive capacities could not only play a substantial role in the pathogenesis of HCV/HIV coinfection but also modulate the response to the standard anti-viral therapy. Materials and Methods: To this end, we studied alterations in frequencies of Treg cells in correlation with other Treg-related and virus-related parameters in both HCV and HCV/HIV-infected patients subjected to standard pegIFN-α/RBV therapy. Results: Notably, we found that pegIFN-α/RBV therapy significantly increased levels of Treg cells in HCV-infected but not in HIV/HCV-coinfected individuals. Furthermore, HIV/HCV-coinfection was demonstrated to inhibit expansion of regulatory T cells during anti-viral treatment; thus, it might probably be responsible for viral persistence and HCV-related liver damage. Conclusions: Therapy with pegIFN-α/RBV demonstrated a significant effect on regulatory T cells in the course of HIV and/or HCV infection indicating a crucial role in the anti-viral immune response. [ABSTRACT FROM AUTHOR]

Introduction: Sustained virological response (SVR) 12 weeks after the end-of-therapy (EOT) has been correlated with SVR24 for HCV-monoinfection. We aim to validate SVR12 as criterion for definition of HCV cure in HIV-coinfected patients treated with all-oral direct-acting antivirals (DAA)., Methods: Prospectively observational study including HIV/HCV-coinfected subjects who received DAA and had HCV-RNA measures at weeks 12 and 24 after EOT. Every patient who took ≥1 drug dose was analyzed., Results: DAA were prescribed to 423 patients, of whom 387 had HCV-RNA measures both at weeks 12 and 24 after EOT. SVR12 was confirmed in 379/387 patients, while SVR24 was confirmed in 377/387 subjects. The positive-predictive-value (PPV) of SVR12 for SVR24 was 99.5% (95%CI: 98.1-99.9). One of the recurrences was clinically suspected to be a late relapse., Conclusions: SVR12 has a high PPV for HCV cure in HIV/HCV-coinfection, though further follow-up could be necessary for those with deeper immunosuppression., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Introduction: Direct-acting antivirals (DAA) have revolutionized the modern treatment of chronic hepatitis C (HCV). These highly efficacious, well-tolerated, all-oral HCV regimens allow cure of HCV in over 95% of HCV-monoinfected as well as HIV/HCV-coinfected patients with short treatment durations of 8-12 weeks., Areas Covered: This review will address recent developments of DAA-therapy in HIV/HCV-coinfected patients in clinical trials and real life cohorts and evaluate remaining challenges, particularly resistance, drug-drug interactions, acute HCV infection and liver transplantation focusing on HIV/HCV-coinfected patients., Expert Opinion: Indeed, all available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection are now the same for both patient populations. HIV/HCV-coinfected patients however, require careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other comedications. The few remaining gaps in DAA-therapy in particular treatment of cirrhotic treatment-experienced genotype 3 infections, decompensated cirrhosis, chronic kidney disease and patients with prior DAA treatment failure have mostly been overcome by the development of new HCV agents recently licensed. Clearly, the biggest challenge globally remains the access to treatment and the inclusion of all patient populations affected in particular people who inject drugs (PWID).