Pegylated IFN-α_2bplus ribavirin for treatment-naive patients coinfected with HCV and HIV

Abstract

Since 1995, after the generalization of highly active antiretroviral therapy (HAART), HCV coinfection in patients with HIV has become a clinical problem of first magnitude. In fact, currently, HCV coinfection is the primary cause of morbi-mortality of AIDS patients in many hospitals. As a consequence, a significant number of clinical trials have been carried out during the past 8-10 years on HCV/HIV-coinfected patients, and have been coincident that the use of pegylated interferon (PEG-IFN) plus ribavirin should be now the gold standard for treating these patients. Various prospective, randomized studies have reached the conclusion that PEG-IFN-alpha(2b) plus ribavirin achieves HCV cure rates in approximately 50% of all patients, together with important clinical consequences, since hepatic illness progression stops or even reverts. Although adverse events are extremely common with this combined treatment, it is also true that their handling by experts means that only 10-15% of patients must abandon treatment.

HIV/Hepatitis C Virus−Coinfected Virologic Responders to Pegylated Interferon and Ribavirin Therapy More Frequently Incur Interferon-Related Adverse Events Than Nonresponders Do

“…Consistent with prior reports of dose-limiting toxicity seen with HCV/HIV co-infected individuals 5, we observed frequent psychiatric symptoms in patients treated with IFN. The principal challenge in characterizing this IFN-related toxicity is the assignment of psychiatric symptoms observed to the effects of medication as opposed to pre-existing mental conditions.…”

“…Several demographic factors can influence the occurrence of adverse events 5. In this regard, there were no statistical differences in the baseline characteristics (race, age, liver disease staging) and treatment characteristics (type of IFN-α, duration of therapy, ribavirin dosing) between the two groups.…”

“…Introduction of antiretroviral therapy [ART], has resulted in decline of HIV related mortality; however HCV-related liver disease has become a leading cause of hospitalization and death 3, 4. The efficacy of pegylated interferon [peg-IFN] plus ribavirin as treatment for HCV infection in co-infected patients has been shown to be much lower than HCV mono-infected patients, particularly in those infected with genotype 1 5. HIV/HCV co-infected patients are also characterized by high rates of drug use and neurocognitive and psychiatric disorders rendering them potentially even more susceptible to the neuropsychiatric adverse events of interferon therapy 6, 7.…”

Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding

“…It will also be important in future studies to determine the efficacy of therapeutic IFN treatment initiated following infection to prevent both morbidity and subsequent transmission of influenza viruses. However, in considering the application of these studies to human treatment during a pandemic, it is important that IFN treatment in humans is associated with a number of adverse side effects (8,45,52), making multiple treatments with high doses of IFN potentially untenable. The appearance of frequent adverse events could be corrected by reducing the total dose of IFN provided during the course of treatment.…”

Proteome‐Wide Anti–Hepatitis C Virus (HCV) and Anti‐HIV Antibody Profiling for Predicting and Monitoring the Response to HCV Therapy in HIV‐Coinfected Patients

“…However, liver disease has become a leading cause of morbidity and mortality in this population [3, 4]. HIV-HCV co-infection is also associated with higher HCV viral levels in serum [5, 6], rapid progression of liver disease [7] and lower efficacy of pegylated interferon [peg-IFN] plus ribavirin treatment [5, 8]. Development of biomarkers that can accurately predict therapeutic responses are needed to optimize HCV therapy in this co-infected population.…”