Antiviral Treatment: A Comprehensive Guide PDF

Antivirals Peter Daley MD MSc FRCPC DTM+H Associate Professor, Memorial University Phase 2 2025 Objectives 11754. Recognize the mechanism of action of antiviral agents 11755. Recognize viral mechanisms of resistance to antiviral agents 11756. Introduce antiviral treatment for i...

Antivirals Peter Daley MD MSc FRCPC DTM+H Associate Professor, Memorial University Phase 2 2025 Objectives 11754. Recognize the mechanism of action of antiviral agents 11755. Recognize viral mechanisms of resistance to antiviral agents 11756. Introduce antiviral treatment for influenza, hepatitis, herpes viruses and COVID-19 Viral Disease Epidemiology Acute Viral Infections Chronic Viral Infections COVID-19 (vaccine preventable) HIV Pandemic 2020-2022, 7 million deaths 65,000 Canadians chronically infected Influenza (vaccine preventable) Hepatitis C Canada annually: 12,200 admissions, 214,000 Canadians chronically infected 3,500 deaths World annually: 250,000 – 500,000 Hepatitis B (vaccine preventable) deaths 262,000 Canadians chronically infected Occasional pandemics World: 360 million chronically infected 2009 Swine Flu H1N1 Herpes Simplex Virus 2025 Avian Flu? 25% of American adults seropositive Antivirals Much more difficult to achieve selective toxicity with intracellular life cycle Target viral enzymes involved in viral replication Target host immune response Being highly mutagenic, viruses escape selection pressure easily Antiviral drugs are ”narrow-spectrum” (specific) Most viral infections are still untreatable (supportive care) Antiviral Mechanisms Target Drug Virus Attachment Peptide analogue of attachment HIV protein Antibodies Many Penetration, Uncoating Pleconaril PicoRNAviruses Transcription, protein synthesis Interferon Papillomaviruses DNA polymerase Nucleoside analogues HIV, Hepatitis, Herpes Nucleoside biosynthesis Ribavirin Respiratory Syncytial Virus Nucleoside scavenging Nucleoside analogues Herpes Protein assembly Protease inhibitors HIV Neuraminidase inhibitors Influenza Viral destruction Nonoxynol-9 HIV Nucleoside Analogue Mechanism Mechanisms of antiviral resistance Mutation in viral target site Viral phosphorylase (herpes viruses) RNA polymerase (hepatitis B) Enzyme (neuraminidase) (influenza) Not like bacteria (prevent drug entry, destroy drug, mutate ribosome, expel drug) Diagnosis of Viral Respiratory Infections Nasopharyngeal swab multiplex PCR 24 hours turnaround, multiple targets, only in St. John’s Nasopharyngeal antigen point of care Few minutes, few targets, not funded Which virus matters! Viruses are not treated with antibacterials! COVID-19  Evidence-Based Medicine New drugs are regulated based on a careful consideration of the evidence for efficacy and safety and cost effectiveness Not based on emergency use authorization Not based on regulatory approval Not based on unpublished data Not based on observational studies Not based on in vitro data Not based on companies giving away supply Not based on a celebrity opinion World Health Organization Living Guidelines https://www.bmj.com/content /370/bmj.m3379 Influenza Influenza Treatment When Influenza virus is circulating Treat for symptoms Treat ASAP (48 hours) for suspected or confirmed (nasopharyngeal swab PCR) patients at risk of death: Severe illness, admissions, chronic medical illness, pregnant, 65 years Oseltamivir PO or Zanamivir inhaled x 5 days Longer for compromised, critical Influenza B is resistant to Oseltamivir Diagnose and treat bacterial coinfection (less likely than is treated) Influenza Prophylaxis (Canada 2023) Institutional influenza outbreaks Isolation, surveillance, prophylaxis Seasonal prophylaxis for high-risk hosts in community Post-exposure prophylaxis for immunosuppressed hosts Hepatitis C Hepatitis C Treatment Treat for cure (all genotypes), prevention of cirrhosis, prevention of transmission Treat all patients (even IVDU) 8-12 week oral treatment leads to sustained viral response Viral load zero at 12 weeks after treatment Fixed dose combination Cost-effective Hepatitis B Interpretation of HBV serology HBSAg positive - chronic HBV, consider treatment HBSAg negative, HBcAb positive, HBSAb positive – cleared HBV HBSAb positive – vaccinated Hepatitis B Treatment Treat to prevent cirrhosis and hepatocellular carcinoma Long term oral nucleotide analogue 60-70% viral load suppression (not cure) Human Herpesviruses 1. Herpes simplex-1 (mucosal ulcers) 2. Herpes simplex-2 (mucosal ulcers) 3. Varicella (chicken pox, shingles) 4. Ebstein-Barr virus (mononucleosis, compromised host) 5. Cytomegalovirus (mononucleosis, compromised host) 6. HHV-6 (Roseola infantum) 7. HHV-7 (Pityriasis rosea) 8. HHV-8 (Kaposi’s sarcoma) Herpesvirus Treatment Treat for symptoms, not cure No treatment, episodic, suppression IV or PO nucleotide analogues Objectives 11754. Recognize the mechanism of action of antiviral agents 11755. Recognize viral mechanisms of resistance to antiviral agents 11756. Introduce antiviral treatment for influenza, hepatitis, herpes viruses and COVID-19