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Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis
Published on: September 11, 2019
Safety considerations in the management of hepatitis C and HIV co-infection
Vicente Soriano1, Víctor Moreno-Torres1,2, Ana Treviño1
1Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain.
Insights
Dual therapy for Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) requires careful management due to potential side effects and drug interactions. Newer direct-acting antivirals (DAA) improve treatment outcomes for coinfected patients.
Area of Science:
- Hepatology and Virology
- Infectious Diseases
- Pharmacology
Background:
- Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) are prevalent global infections affecting millions.
- Oral antivirals offer curative potential for HCV and disease management for HIV.
- Coinfected patients require specialized expertise for dual therapy.
Purpose of the Study:
- To review challenges and strategies for dual HCV/HIV therapy.
- To highlight advancements in direct-acting antivirals (DAA) for coinfected individuals.
- To outline management considerations for potential complications.
Main Methods:
- Literature search of PubMed from January 2010 to March 2023.
- Review of challenges including side effects, HBV reactivation, IRIS, and drug-drug interactions (DDI).
- Analysis of DAA and antiretroviral (ARV) interactions.
Main Results:
- Second-generation DAAs offer improved potency, safety, and pangenotypic activity for HCV treatment in coinfected patients.
- Sequential initiation of ARV then DAA is generally preferred.
- Key challenges include overlapping side effects, HBV reactivation, IRIS, and significant DDIs affecting drug metabolism (CYP450) and transporters.
Conclusions:
- Dual therapy for HCV/HIV is feasible with newer DAAs, but requires careful monitoring.
- Management strategies should address potential DDIs, HBV reactivation, and IRIS.
- Attention to renal function is crucial when using nucleos(t)ide analogues.
Introduction:
Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise.
Areas Covered:
Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023.
Expert Opinion:
The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.
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