Effects of Pegylated Interferon Alpha and Ribavirin (pegIFN-α/RBV) Therapeutic Approach on Regulatory T Cells in HCV-Monoinfected and HCV/HIV-Coinfected Patients

Abstract

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.

Mpox (formerly monkeypox): pathogenesis, prevention and treatment

“…[200][201][202] Ribavirin also stimulates the generation of central memory T-cells and Tregs. 203,204 Pidotimod is an immunomodulator used as an adjunctive therapy for respiratory or urinary tract infections. 205 It promotes non-specific and specific immune responses by activating NK cells, stimulating lymphocyte proliferation, and inducing the release of IL-1β and IFN-γ.…”

Polyethylene Glycol-Modified Cationic Liposome as a Promising Nano Spray for Acute Pneumonia Treatment

“…Ribavirin (RBV) is a monophosphate inosine 5 ′ -monophosphate (IMPDH) inhibitor that inhibits IMPDH, thereby hindering the synthesis of viral nucleic acids. RBV has broad-spectrum antiviral properties, inhibiting a wide range of viruses such as respiratory syncytial virus, influenza virus, herpes simplex virus, and preventing influenza, adenovirus pneumonia, hepatitis A, herpes, and measles [2][3][4]. In China, RBV has been clinically proven to be effective against epidemic hemorrhagic fever, and its efficacy is obvious in early-stage patients, which can reduce the mortality rate, alleviate renal damage, reduce bleeding tendency, and improve systemic symptoms [5].…”

“…In China, RBV has been clinically proven to be effective against epidemic hemorrhagic fever, and its efficacy is obvious in early-stage patients, which can reduce the mortality rate, alleviate renal damage, reduce bleeding tendency, and improve systemic symptoms [5]. However, RBV has some common problems, such as a short blood half-life and being easy to be metabolized by the human liver and kidney [3,5]. In addition, unmodified RBV is easily digested, unstable in vivo, and prone to unexpected biological reactions [6].…”

Combined Effects of Fludarabine and Interferon Alpha on Autophagy Regulation Define the Phase of Cell Survival and Promotes Responses in LLC-MK2 and K562 Cells

“…Moreover, administration of IFN-α is considered worthwhile against other human life-threatening viruses, including human immunodeficiency virus (HIV) and emerging viruses such as some coronaviruses. Although studies of patients infected with HIV indicate that IFN-α could not inhibit HIV latency and may cause neurotoxicity [ 24 , 25 ], IFN-α treatment demonstrated a profound event of immunity stimulation, especially in cell-mediated immune responses of HIV-infected cells [ 26 , 27 ]. During the recent COVID-19 pandemic, IFN-α has received considerable attention as an anti-COVID-19 treatment.…”