Sandbox JA

Progress

Antiviral Agents Used in the Treatment of Hepatitis C

Agent	Recommended Dose	Adverse Effects
PegIFN alfa-2a (Pegasys™)	180 mcg subcutaneously once weekly	Serious adverse events: <1% Depression with suicide Relapse of drug abuse/overdose Severe bacterial infections (osteomyelitis, endocarditis, pyelonephritis, pneumonia, and sepsis) Hepatic decompensation (2% of patients with HIV coinfection) Common adverse events: 99% of patients experience at least one of the following Psychiatric reactions, including depression, insomnia, irritability, anxiety Flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors Anorexia Nausea and vomiting Diarrhea Arthralgias Injection site reactions Alopecia Pruritus
PegIFN alfa-2b (PEG-Intron™)	1.5 mc / kg SC once weekly	Serious adverse events: <1% Suicidal/homicidal thoughts Cardiovascular events Loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis Stroke Bone marrow toxicity Development or exacerbation of autoimmune disorders Colitis Pancreatitis Pulmonary disorders including dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans Liver failure especially with HIV coinfection Common adverse events: 50% of patients have at least one of the following Injection site reaction Mood instability and depression Nausea Fatigue/asthenia Headache Rigors and fevers Myalgia
Ribavirin (Rebetol™, Ribasphere™, Copegus™, RibaPak™)	Genotype 1 1,000 mg (if ≤ 75 kg) or 1,200 mg (if > 75 kg) PO daily divided into two doses Genotype 2 & 3 800 PO daily in two divided doses	Ribavirin is teratogenic and may cause birth defects and/or death of the exposed fetus. Serious adverse events: Bacterial infection (sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia) (3-5%) Hemolytic anemia (13%) Pancreatitis Liver failure Pulmonary disease Common adverse events: Fatigue/asthenia Fever Myalgias Headaches
Sofosbuvir (Sovaldi™)	400 mg orally daily	Common adverse events: 20% Fatigue Headache Insomnia Anemia
Simeprevir (Olysio™)	150 mg orally daily	Common adverse events: 20% Rash Photosensitivity Pruritus Nausea Dyspnea
Boceprevir [BOC] (Victrelis™)	800 mg (4 × 200 mg capsules) PO every 7 – 9h with food in combination with PegIFN – RBV following a 4-week lead-in with PegIFN – RBV No longer recommended given the safer profile of newer protease inhibitors	Serious adverse events: Anemia Neutropenia Pancytopenia Common adverse events: Fatigue Anemia Nausea Headache Dysgeusia
Telaprevir [TVR] (Incivek™)	750 mg (2 × 375 mg tablets) PO every 7 – 9 h with food (20 grams fat) for 12 weeks, plus PegIFN – RBV 24 or 48 weeks No longer recommended given the safer profile of newer protease inhibitors	Serious adverse events: Stevens Johnson Syndrome (SJS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Toxic Epidermal Necrolysis (TEN) Profound anemia Common adverse events: Rash Pruritus Fatigue Anemia Nausea and vomiting Hemorrhoids Diarrhea Anorectal discomfort Dysgeusia Anal pruritus

Antiviral Medications

There are three types of treatment groups:

1. Interferon (IFN)
2. Nucleoside analogs
3. Nucleotide analogs

First Line agents

Entecavir (ETV)

• An anti-HBV nucleoside analog
• A 94% clearance rate after 5 years of treatment is observed in HBeAg positive patients.
• A 90% clearance rate after 48 weeks of treatment is observed in HBeAg negative patients.
• A necroinflammation improvement of 96% and fibrosis improvement of 88% is seen after a treatment for 6 years.

Tenofovir (TDF)

• An anti-HBV nucleotide analog
• A 68% clearance rate in HBV DNA after 4 years of treatment is observed in HBeAg positive patients.
• A 84% clearance rate in HBV DNA after 4 years of treatment is observed in HBeAg negative patients.

Interferons

• Antiviral and antiproliferative glycoprotein.
• No antiviral resistance have been noted
• Best results noted with genotype A or B who are HBeAg positive.

Second line agents

Telbivudine (LDT)

• Nucleoside analog
• Worse resistance than first line agents and not indicated if resistance to other nucleoside analogs are noted.

Adefovir (ADV)

• Nucleotide analog
• Worse resistance than first line agents
• Used in cases of nucleotide analog resistance.

Lamivudine

• Nucleoside analog
• Has a high rate of resistance and hence not used currently.

Pathogenesis

Treatment

When listeric meningitis occurs, the overall mortality may reach 70%; from septicemia 50%, from perinatal/neonatal infections greater than 80%. In infections during pregnancy, the mother usually survives. Reports of successful treatment with parenteral penicillin or ampicillin exist. Trimethoprim-sulfamethoxazole has been shown effective in patients allergic to penicillin.

Bacteriophage treatments have been developed by several companies. EBI Food Safety and Intralytix both have products suitable for treatment of the bacteria. The FDA of the United States approved a cocktail of six bacteriophages from Intralytix, and a one type phage product from EBI Food Safety designed to kill the bacteria L. monocytogenes. Uses would potentially include spraying it on fruits and ready-to-eat meat such as sliced ham and turkey.

Table

Disease	Findings
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