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Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice
Published on: October 6, 2022
HCV and HIV co-infection: mechanisms and management
Jennifer Y Chen1, Eoin R Feeney2, Raymond T Chung1
1Liver Center and Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Insights
Hepatitis C (HCV) and HIV co-infection accelerates liver disease. New direct-acting antiviral agents offer a chance to improve treatment for co-infected patients.
Area of Science:
- Hepatology and Virology
- Immunology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection accelerates liver fibrosis and increases mortality.
- HIV exacerbates HCV progression through increased viral replication, inflammation, apoptosis, and impaired immunity.
- Liver disease is a primary cause of non-AIDS mortality in HIV-infected individuals.
Purpose of the Study:
- To review mechanisms of accelerated liver disease in HCV/HIV co-infection.
- To evaluate current treatment limitations for co-infected patients.
- To explore future treatment paradigms incorporating direct-acting antivirals.
Main Methods:
- Literature review of mechanisms driving accelerated liver disease.
- Analysis of treatment outcomes for HCV/HIV co-infected patients.
- Discussion of emerging direct-acting antiviral therapies.
Main Results:
- HIV infection significantly worsens HCV-related liver disease progression.
- Current interferon-based HCV treatments show inferior efficacy in co-infected patients.
- Direct-acting antivirals (DAAs) represent a promising new therapeutic avenue.
Conclusions:
- Novel treatment strategies are needed for HCV/HIV co-infection.
- Future regimens should consider fibrosis stage and antiretroviral drug interactions.
- DAAs hold potential to redefine treatment for this population.
Abstract:
HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS-related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut and leads to an impairment of HCV-specific immune responses. Treatment of HIV with antiretroviral therapy and treatment of HCV have independently been shown to delay the progression of fibrosis and reduce complications from end-stage liver disease among co-infected patients. However, rates of sustained virologic response with PEG-IFN and ribavirin have been significantly inferior among co-infected patients compared with HCV-monoinfected patients, and treatment uptake has remained low given the limited efficacy and tolerability of current HCV regimens. With multiple direct-acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.
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