scholarly journals Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy

2020 ◽  
Vol 222 (4) ◽  
pp. 601-610
Author(s):  
Ashwin Balagopal ◽  
Laura M Smeaton ◽  
Jeffrey Quinn ◽  
Charles S Venuto ◽  
Gene D Morse ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C ◽  
Rank Correlation ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Direct Acting Antivirals ◽  
Viral Kinetics ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Direct Acting

Abstract Background Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection. Methods We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S. Results Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by −4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%–42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%–1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = −160 pg/mL per day at 24 hours, but no further after Day 4. Conclusions We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.

scholarly journals Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

2021 ◽  
Author(s):  
Natthaya Chuaypen ◽  
Thananya Jinato ◽  
Anchalee Avihingsanon ◽  
Sakkarin Chirapongsathorn ◽  
Supapon Cheevadhanarak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gut Microbiota ◽  
Alpha Diversity ◽  
Healthy Controls ◽  
Direct Acting Antivirals ◽  
Microbial Dysbiosis ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

scholarly journals A Treatment-as-Prevention Trial to Eliminate Hepatitis C Among Men Who Have Sex With Men Living With Human Immunodeficiency Virus (HIV) in the Swiss HIV Cohort Study

2020 ◽  
Author(s):  
Dominique L Braun ◽  
Benjamin Hampel ◽  
Bruno Ledergerber ◽  
Christina Grube ◽  
Huyen Nguyen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cohort Study ◽  
Hepatitis C ◽  
Population Based ◽  
Hcv Infection ◽  
World Health ◽  
Treatment As Prevention ◽  
Hcv Rna ◽  
Immunodeficiency Virus ◽  
Sex With Men

Abstract Background In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population. Methods During phase A (10/2015–06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016–02/2017) we offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017–11/2017), we offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections. Results We screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. We rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35–.83) prior to the intervention to .12 (95% CI, .03–.49) by the end of 2019. Conclusions A systematic, population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets. Clinical Trials Registration NCT02785666.

scholarly journals The Impact of Direct-Acting Antivirals in the Hepatitis C-Sustained Viral Response in Human Immunodeficiency Virus-Infected Patients With Ongoing Barriers to Care

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Edward R. Cachay ◽  
David Wyles ◽  
Lucas Hill ◽  
Craig Ballard ◽  
Francesca Torriani ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C ◽  
Barriers To Care ◽  
Sustained Viral Response ◽  
Treatment Protocol ◽  
Direct Acting Antivirals ◽  
Hcv Treatment ◽  
Viral Response ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background.  Access to hepatitis C virus (HCV) medications for human immunodeficiency virus (HIV)-infected patients with ongoing barriers to care is restricted by healthcare payers in the absence of HCV treatment outcomes data in the era of direct-acting antivirals (DAA). Methods.  Retrospective analysis of HCV treatment outcomes using interferon (IFN)-free DAA regimens and an inclusive treatment protocol in an urban HIV clinic where ongoing barriers to care (drug or alcohol use, psychiatric disease, and/or unstable housing) are common. Then, using logistic regression analysis, we compared the proportion of HIV-infected patients who achieved HCV sustained viral response (SVR) in the pegylated-IFN plus ribavirin (PEG-IFN/RBV, 2008–2011), pegylated-IFN plus ribavirin and telaprevir (PEG-IFN/RBV/PI, 2011–2013), and IFN-free DAA therapy eras (2014). Results are displayed using forest plots. Results.  The proportion of patients who achieved HCV SVR in the PEG-IFN/RBV, PEG-IFN/RBV/PI, and IFN-free DAA therapy eras increased from 38.4% (95% confidence interval [CI], 23.2–53.7) and 48% (95% CI, 28.4–67.6) to 83.3% (95% CI, 70.0–96.7), respectively. Similar proportions of patients with ongoing barriers to care were treated during the PEG-IFN/RBV (25 of 39 [64%]), PEG-IFN/RBV/PI (14 of 25 [56%]), and IFN-free DAA (16 of 30 [53%]) eras. Hepatitis C virus SVR among patients with ongoing barriers to care improved from 40% (95% CI, 21–59) to 76.5% (95% CI, 56–97) in the PEG-IFN/RBV and IFN-free DAA eras, respectively. After stratification for factors associated with HCV SVR such as HCV genotype and cirrhosis, HCV SVR were similar in patients regardless of the presence of ongoing barriers to care. Conclusions.  Using IFN-free DAA and an inclusive HCV treatment protocol, 76.5% of HIV/HCV-treated patients with ongoing barriers to care achieved HCV SVR.

scholarly journals Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Yanina Ghiglione ◽  
María Laura Polo ◽  
Alejandra Urioste ◽  
Ajantha Rhodes ◽  
Alejandro Czernikier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiretroviral Therapy ◽  
Direct Acting Antivirals ◽  
Hiv Persistence ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Hcv Coinfection ◽  
Direct Acting

Abstract Background Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). Methods In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. Results Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. Conclusions Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

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