Pathology 22

• Antiviral resistance can be defined as a decreased susceptibility to a drug caused by changes in viral genotypes.
• Direct-acting Antivirals include Ledipasvir, Sofosbuvir, Simeprevir, Telaprevir, Boceprevir.
• In cases of antiviral resistance, drugs have either diminished or no effectiveness against their target virus.
• RNA viruses, such as Hepatitis C virus, have an error-prone RNA polymerase and no correction mechanism.
• DNA viruses, such as Hepatitis B virus, have most DNA polymerases that can excise and replace misincorporated nucleotides.
• Resistance happens to any antiviral drug.
• DNA viruses evolve more slowly than RNA viruses.
• Hepatitis C virus is treated with Daclatasvir, Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir, Interferon, Pegylated interferon, Ribavirin, leading to shorter treatment times and higher cure rates with fewer side effects.
• Special concern during extended therapy for chronic infections (HIV, HBV, HCV)
• As viruses replicate, modest-to-high mutation frequencies happen.
• Patients can now live long, active lives with HIV.
• Abacavir, Delavirdine, Atazanavir, Raltegravir, Maraviroc, Didanosine, Efavirenz, Darunavir, Dolutegravir, Emtricitabine, Nevirapine, Fosamprenavir, Elvitegravir, Fusion inhibitor, Lamivudine, Rilpivirine, Indinavir, Enfuvirtide, Stavudine, Doravirine, Lopinavir/ritonavir, Tenofovir, Nelfinavir, Entry inhibitor, Zidovudine, Ritonavir, Ibalizumab, Saquinavir, Tipranavir.
• The goals for anti-HIV medicines are to: Maximal and durable suppression of viral load, Restoration and/or preservation of immunologic function, Improvement of quality of life, Reduction of HIV-related morbidity and mortality.
• This strategy disrupts HIV replication at many stages.
• The higher the CD4 cell count, the lower the risk of becoming ill because of HIV.
• Foscarnet – Second - line therapy for patients who do not tolerate ganciclovir treatment – Used in drug-resistant CMV infections – CMV retinitis.
• Treatment options for HIV are much better than they were a few decades ago.
• Cidofovir – Used mainly in CMV retinitis in AIDS patients.
• Reducing HIV in the blood allows the immune system (CD4 cell) to strengthen.
• Another benefit of reducing HIV in the blood is it prevents transmission because the viral load is undetectable.
• Potential carcinogen Oral (bioavailability 5%), Intravenous Ophthalmic slow - release preparation Valganciclovir prodrug for ganciclovir commonly associated with vomiting, abdominal pain, diarrhea, and headache Oral (bioavailability 60%) Foscarnet structural mimic of the anion pyrophosphate that selectively inhibits the pyrophosphate binding site on viral DNA polymerases Nephrotoxicity, electrolyte disturbances Intravenous Cidofovir inhibits viral replication by selectively inhibiting viral DNA polymerases Nephrotoxicity intravenous● Ganciclovir – Used in CMV retinitis in severely immunocompr
• A combination, or "cocktail," of drugs is the best way to control HIV and lower the chances of HIV becoming resistant to treatment.
• Most people take a combination of three antiretroviral medications, although a two-drug combination is now also possible.
• There's no cure for HIV.
• The development of antiviral drugs is still way behind antibacterial drugs.
• It is difficult to inhibit viral replication without toxicity to the host.
• In recent years, there are many antiviral agents and many more are undergoing testings and clinical trials, due to knowledge in the structure and functions of the viral proteins and major advances in the techniques in drug discovery.
• The first step in antiviral design is to identify viral proteins, or parts of proteins, that can be disabled.
• Once targets are identified, candidate drugs can be selected, either from drugs already known to have appropriate effects or by actually designing the candidate at the molecular level with a computer-aided design program.
• Recombinant technologies are often used to manufacture the target proteins for testing.
• Potential targets for antiviral drugs include virus need a host to multiply, release of viral particles to infect new host cells, attachment to a host cell, uncoating, release of viral genes, replication and translation of viral genes into proteins, and assembly of viral components into complete viral particles.
• Antiviral drugs are used in the following infections: Herpes simplex virus, Varicella zoster virus, Cytomegalovirus, Human immunodeficiency virus, Influenza A & B virus, Respiratory Syncytial Virus, Hepatitis B virus, Hepatitis C virus.
• Herpes simplex virus is categorized into 2 types: HSV - 1 and HSV - 2.
• HSV - 1 is mainly transmitted by oral-to-oral contact and causes oral herpes (“cold sores”) and sometimes genital herpes.
• HSV - 2 is sexually transmitted and causes genital herpes.
• Both HSV - 1 and HSV - 2 infections are lifelong.
• Drugs used to treat HSV include Acyclovir, Valacyclovir, and Famciclovir.
• Acyclovir is a nucleoside analogue that mimics guanosine, resulting in a decrease in the production of viral DNA.
• Valacyclovir and Famciclovir are prodrugs of Acyclovir.
• Acyclovir is generally safe and well tolerated.