Antiviral Drugs | Medical Science Optional Notes for UPSC PDF Download

Antiviral Drugs - Classification

1. Antiviral Medications for Herpes Virus:

• Idoxuridine
• Trifluridine
• Acyclovir
• Valacyclovir
• Famciclovir
• Ganciclovir
• Valganciclovir
• Cidofovir
• Foscarnet
• Fomivirsen

2. Antiviral Medications for Influenza Virus:

• Amantadine
• Rimantadine
• Oseltamivir
• Zanamivir

3. Antiviral Medications for Hepatitis Virus/Nonselective Antiviral Drugs:

• Primarily for Hepatitis B: Lamivudine, Adefovir dipivoxil, Tenofovir
• Primarily for Hepatitis C: Ribavirin, Interferon α

4. Antiviral Medications for Retrovirus:
(a) Nucleoside reverse transcriptase inhibitors (NRTIs):

• Zidovudine (AZT)
• Didanosine
• Stavudine
• Lamivudine
• Abacavir
• Emtricitabine
• Tenofovir (Nt RTI) 

(b) Non-nucleoside reverse transcriptase inhibitors (NNRTIs):

• Nevirapine
• Efavirenz
• Delavirdine 

(c) Protease inhibitors:

• Ritonavir
• Atazanavir
• Indinavir
• Nelfinavir
• Saquinavir
• Amprenavir
• Lopinavir 

(d) Entry (Fusion) inhibitor:

• Enfuvirtide 

(e) CCR5 receptor inhibitor:

• Maraviroc 

(f) Integrase inhibitor:

• Raltegravir

Anti-Herpes Virus Drugs

Anti-Influenza Virus Drugs

• Amantadine
• Rimantadine
• Oseltamivir
• Zanamivir

Amantadine is no longer advised for influenza treatment. While it was previously considered an option for treating influenza A, during the 2008/2009 flu season, the CDC discovered that all seasonal H3N2 and 2009 pandemic viruses had developed resistance to amantadine.

Antiviral Agents (Viral Hepatitis)

Replication Cycle of HIV

(a) Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Didanosine, Stavudine, Lamivudine, Abacavir, Emtricitabine, Tenofovir (Nt RTI)
(b) Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Nevirapine, Efavirenz, Delavirdine
(c) Protease inhibitors: Ritonavir, Atazanavir, Indinavir, Nelfinavir, Saquinavir, Amprenavir, Lopinavir
(d) Entry (Fusion) inhibitor: Enfuvirtide
(e) CCR5 receptor inhibitor: Maraviroc
(f) Integrase inhibitor: Raltegravir

• HIV gains entry into the body (e.g., through mucosal lesions or infection of mucosal/cutaneous immune cells), subsequently binding to target cells' CD4 receptor using its gp120 glycoprotein.
• The viral envelope merges with the host cell, allowing the capsid to enter the cell.
• Fusion requires the presence of both the CD4 receptor and a coreceptor (CCR5 in macrophages, and either CCR5 or CXCR4 in T-cells).
• Individuals lacking CCR5 receptors exhibit resistance to HIV; these individuals may possess either a homozygous CCR5 mutation (providing substantial resistance) or a heterozygous CCR5 mutation (resulting in a slower disease course).
• The virion's RNA undergoes transcription into DNA, which is then integrated into the host's DNA.
• Viral DNA replication occurs, leading to the assembly of new virions.
• The virion repurposes a portion of the cell's membrane to form an envelope and exits the cell through budding, ultimately causing cell death.

Tenofovir

Derived from adenosine monophosphate, Tenofovir is a nucleotide analog, classifying it as a nucleotide reverse transcriptase inhibitor (NtRTI).

Side Effects of NRTIs

Side Effects of NNRTIs

Side Effects of Protease Inhibitors

Side effects of Integrase Inhibitors

HAART

Combination antiretroviral therapy (cART), also known as highly active antiretroviral therapy (HAART), stands as the fundamental approach in managing individuals with HIV infection. In the past, anti-HIV drugs were administered sequentially as monotherapy, with each drug being used after the failure of the preceding one due to the emergence of resistance. However, a comprehensive understanding of HIV infection biology, coupled with the availability of potent drugs from various classes, has necessitated the adoption of 'highly active antiretroviral therapy' (HAART). This involves combining three or more drugs whenever indicated.

Monotherapy is contraindicated.

• Recommended regimens 
• 3 NRTI (e.g., zidovudine, lamivudine, abacavir) OR
• 2 NRTI (e.g., lamivudine + abacavir) AND 
  • 1 NNRTI (e.g., efavirenz) OR 
  • 1 PI (e.g., lopinavir) OR 
  • 1 INI (e.g., raltegravir)

NACO Art Guidelines

[Question: 936565]

Note: The current recommendation is to initiate all people living with HIV (PLHIV) and HIV-1 infection on a regimen that includes TENOFOVIR (TDF 300 mg) + LAMIVUDINE (3TC 300 mg) + EFAVIRENZ (EFV 600 mg) (TLA) as a Fixed Dose Combination (FDC) in a single pill once a day. This regimen offers the advantage of uniformity in the treatment approach for adults, adolescents, pregnant women, as well as those with HIV-TB and HIV-hepatitis co-infections.
For patients with HIV-2 infection (whether HIV-2 alone or co-infections with both HIV-1 and HIV-2), the recommended first-line ART regimen is Tenofovir (300 mg) combined with Lamivudine (300 mg) and Lopinavir/Ritonavir (800/200 mg).

Antiviral - Repeats

• Provide details on the drug treatment for HIV infection, including the drug names, doses, and associated toxicities. (2003)
• Explain the mechanism of action of retroviral drugs during various stages of HIV replication and discuss their toxicities. (2007)
• List the components of antiretroviral therapy for HIV-infected adults. (2009)