Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.

Treatment outcomes of HIV patients with hepatitis B and C virus co-infections in Southwest China: an observational cohort study

Background Antiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART. Methods A retrospective cohort study analysis of 58 239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010–2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH. Results Our study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI) 2.88–3.02] and 5.92 (95% CI 5.82–6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR) = 1.42; 95% CI 1.32–1.54], HCV-co-infected patients had 65% higher mortality (aHR = 1.65; 95% CI 1.47–1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR = 2.23; 95% CI 1.87–2.66). Conclusions HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH. Graphical Abstract

The experience of the Moscow City Center for AIDS Prevention and Treatment of using glecaprevir/pibrentasvir in patients with HIV/HCV coinfection

The aim of the study is to analyze the experience of the Moscow Center for HIV/AIDS Prevention and Treatment on antiviral therapy of chronic hepatitis C in patients with HIV/ HCV coinfection in real-world evidence (RWE).Methods. The data from the outpatient cards of 12 adults and 53 children with HIV/HCV in the Moscow Center for HIV/AIDS Prevention and Treatment were analyzed for the period from 2020 to October 2021. In addition to standard laboratory tests, the viral load of HIV RNA, HCV RNA was examined in all patients, the HCV genotype was determined, the degree of liver fibrosis was assessed by liver fibroelastometry.Results: Among adult patients 10 (83,4%) were infected with HCV Gt 3, while 2 patients (16,6%) had Gt 1a/3. 5 (41,7%) patients were treatment-naïve and 7 (58,3%) had previously received sofosbuvir and daclatasvir. All 12 adult patients received glecaprevir/pibrentasvir for 8-16 weeks, depending on the treatment experience. 3 (25%) patients with HCV Gt 3 previously treated with DAAs received triple combination of glecaprevir/pibrentasvir, sofosbuvir and ribavirin for 12 weeks. As a result, 100% (12/12) of patients treated with glecaprevir/pibrentasvir achieved SVR12, no adverse events or cases of intolerance were identified.In the general group of adolescents with HCV/HIV coinfection (n = 53), the distribution by HCV genotypes was as follows: Gt 1 – 26 (49%), Gt 3 – 27 (51%). 15 (28,3%) adolescents received interferon-2a (SVR – 40% (6/15)), 9 adolescents received Peg-interferon-2a (SVR – 33% (3/9)) and 16 adolescents received glecaprevir/pibrentasvir. The mean duration of HIV/HCV coinfection in 16 adolescents receiving glecaprevir/pibrentasvir was 12,5 (1-17) years. Of these, 11 (68,3%) were infected with HCV Gt 1 and 5 (31,7%) with HCV Gt 3. 11 patients (68,3%) had prior treatment history with interferon and peginterferon regimens. The distribution of fibrosis stages was as follows: F0 – 56,3% (9/16), F1 – 31,3% (5/16), F2 – 12,4% (2/16). All 16 adolescents received 8 weeks of glecaprevir/pibrentasvir. 100% of patients were aviremic after 4 weeks from the start of therapy. All patients achieved SVR12. No adverse events and/or intolerance of glecaprevir/ pibrentasvir were identified.Conclusion. This observation demonstrates the high efficacy and safety of treatment with direct-acting antiviral drugs in both adults and children with HIV/HCV coinfection. Diagnosis and treatment of chronic hepatitis C in patients of reproductive age with HIV/HCV coinfection before pregnancy will help to completely eliminate the risk of mother-to-child transmission of HCV. Timely, effective, and modern antiviral therapy of already infected adolescents with HCV will make it possible to take a step towards eliminating hepatitis C through microelimination in the described socially significant groups of patients

CCR5+ T-Cells Homed to the Liver Exhibit Inflammatory and Profibrogenic Signatures in Chronic HIV/HCV-Coinfected Patients

Liver fibrosis is accelerated in patients coinfected with hepatitis C virus and human immunodeficiency virus (HIV), compared with HCV monoinfected patients, although the underlying mechanisms are unknown. We hypothesize that T cells expressing the HIV co-receptor, chemokine receptor 5 (CCR5), preferentially migrate to the inflamed liver and contribute to enhanced fibrogenesis. We compared the peripheral and intrahepatic CCR5 expression on CD4+ and CD8+ T cells in 21 HIV/HCV-coinfected patients with 14 chronic HCV monoinfected patients. Using 12-color flow cytometry, phenotypic and functional characterization of CCR5+ and negative cells pre- and post-stimulation with HCV genotype specific overlapping pooled peptides was conducted. Patients with HIV/HCV coinfection had significantly more CD4+CCR5+ and CD8+CCR5+ T cells in the liver as compared with peripheral blood (p = 0.0001 for both). Compared with patients with HCV monoinfection, patients with HIV/HCV coinfection also had fewer peripheral CD4+CCR5+ and CD8+CCR5+ T cells (p = 0.02, p = 0.001 respectively), but more intrahepatic CD4+CCR5+ and CD8+CCR5+ cells (p = 0.0001 for both). Phenotypic analysis of CCR5+ sorted cells demonstrated an increased expression of markers of exhaustion, senescence, immune activation and liver homing (PD1, CD57, CD38, HLADR, and CXCR3). Post-stimulation with HCV peptides, CCR5+ T cells secreted more proinflammatory and profibrogenic cytokines and chemokines rather than antiviral cytokines. Phenotypic and functional analyses of CCR5+ T cells in HIV/HCV-coinfected patients revealed a pathogenic role for CCR5+ T cells in hepatic fibrogenesis. These cells are functionally proinflammatory, pro-fibrogenic and preferentially accumulate in liver, accelerating fibrosis. These findings suggest that targeting CCR5 may be a therapeutic strategy for be ameliorating liver fibrosis.

Zero Prevalence of HIV and HCV Coinfection in the Highly HIV-infected Population of Rivers State, Nigeria

Background: Hepatitis C affects 5–15% of the 38 million people living with HIV globally. Africa which has the second highest prevalence of HIV/HCV co-infection following Asia. This alarming statistics has made it crucial that studies be done to also ascertain the HIV/HCV co-infection prevalence in the country and host factors which may influence the co-infection. Objective: Therefore, this study was conducted to investigate the seroprevalence of HCV infection amongst the HIV population of Rivers state, Nigeria. Study Design: Cross-sectional study. Place and Duration of Study: University of Port Harcourt Teaching Hospital (UPTH), in Rivers State, Nigeria, from February 2017 to September 2019. Methods: In this study, 226 HIV-infected individuals were recruited comprising 105 males and 121 females. These subjects were screened for the presence of HIV and HCV using ELISA and was performed according to the kit manufacturer’s stipulations. The demographic characteristics of the participants were obtained using a questionnaire designed for the study. Results: The presence of antibodies to HIV-1 reconfirmed the HIV status in all the study subject. A seroprevalence rate of 0.0% was observed for HIV/HCV infection. The ratio of females to males was found to be 1.2:1. The ages of the study population ranged from 16 to 70 years with a median age of 42.5 years. A large number (30.5%, n = 69) of the participants were within the age group 40 – 49 years, followed by those within 30 – 39 years (26.1%, n= 59), 50 – 59 years (17.3%, n = 39) and >59 years (13.7%, n = 31). Participants that were within younger age groups had less population; 20 – 29 years (9.7%, n = 22), with those that are <20 years having the least population (2.7%, n = 6). Many (49.1%, n = 111) of the study participants were found to be married. About 46.5% (n = 105) of them were single, while a few (4%, n = 10) were widowed. Conclusion: No coinfection of HIV/HCV was found, in spite of Nigeria being endemic for HCV. However, despite this zero rate of HIV/HCV coinfection, routine screening for HCV markers should be carried out to reduce morbidity and mortality in HIV-infected individuals.

SEROPREVALENCE OF HIV, HBV, AND HCV AMONG INDIVIDUALS ATTENDING ICTC OF A TERTIARY CARE HOSPITAL IN NORTHERN INDIA.

Introduction: Hepatitis B and Hepatitis C share common transmission routes with HIV and coinfection with either can lead to adverse clinical outcomes in patients. This study planned to estimate confections with HBV and HCV among HIV positive subjects at a single Integrated Testing and Counselling Center (ICTC) in Kashmir valley. Methods: The study employed a cross-sectional study design from 2017 to 2019. After pretest counselling all subjects underwent HIV testing as per National AIDS Control guidelines. HIV positive subjects were included in this study. Samples of HIV positive subjects were then tested for HBV by ELISA detecting HbsAg whereas HCV was diagnosed by Anti HCV antibodies and HCV-RNA. Data was entered in excel and analyzed using SPSS. Means and percentages were calculated for relevant variables. Results:Atotal of 20070 subjects were tested during the study period of which 34 (0.169%) were HIVpositive. Around 60% positive subjects were males. Co-infection with HBV was detected in 11.7% subjects whereas 8.8% had an HCV coinfection. One subject had coinfection with both HBV and HCV. There was no signicant association of coinfection with gender or age Conclusion:Considering the adverse impact of coinfection on disease course and outcome, screening for HBVand HCVshould be a component in diagnostic workup of all HIVpositive subjects followed by linkage with specialized treatment services

Concurrent treatment of HIV, disseminated Mycobacterium avium complex and HCV-infection

Patients with HIV-infection diagnosed at late stages usually have significant immunosuppression and demand simultaneous antiretroviral therapy and treatment of opportunistic infections. The presence of HCV coinfection makes treatment even more challenging because of possible adverse effects and drug-drug interactions. HCV cure in such clinical situations not only prevents fibrosis progression, but can also enhance virologic and/or immunologic response to antiretrovirals and thus effective treatment of opportunistic infections. Thorough consideration of all existing diseases and drug interactions of the combined therapy makes simultaneous treatment of HIV, chronic hepatitis C, and opportunistic infections not only possible but the best way to improve outcomes in a complex clinical situation.

A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.