Pharmacology of HIV/AIDS Drugs

Pharmacology of HIV/AIDS Drugs

• This field explores the pharmacological properties and action mechanisms of drugs used to treat HIV/AIDS, a major global pandemic.

Introduction to HIV/AIDS

• HIV (Human Immunodeficiency Virus): A retrovirus attacking the immune system, leading to AIDS if untreated.
• AIDS (Acquired Immunodeficiency Syndrome): The advanced stage of HIV infection, marked by opportunistic infections.
• Global Impact: HIV/AIDS remains a significant global public health concern, affecting millions.

Overview of HIV Life Cycle

• Entry: HIV binds to and fuses with host cells, injecting its genetic material.
• Replication: The viral genome integrates into the host cell's DNA, leading to the creation of new virus particles.
• Release: New viral particles bud from the host cell, ready to infect other cells.

Antiretroviral Drug Classes

• NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors): Interfere with reverse transcription, preventing viral DNA synthesis.
• NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors): Bind directly to reverse transcriptase, blocking its activity.
• Pls (Protease Inhibitors): Disrupt the processing of viral proteins, preventing the formation of infectious viral particles.

Mechanism of Action of NRTIs

• Structural Similarity: NRTIs mimic natural nucleosides, allowing incorporation into the growing viral DNA chain.
• Chain Termination: Lacking a 3' hydroxyl group, NRTIs halt DNA synthesis.
• Competitive Inhibition: NRTIs compete with natural nucleosides for reverse transcriptase binding.

Mechanism of Action of NNRTIs

• Binding to Reverse Transcriptase: NNRTIs bind to a specific pocket on reverse transcriptase, not the active site.
• Conformational Changes: Binding alters the enzyme's conformation, preventing its catalytic activity.
• Inhibition of DNA Synthesis: By inhibiting reverse transcriptase, NNRTIs halt viral DNA synthesis.

Mechanism of Action of Pls

• Protease Inhibition: Pls target HIV protease, essential for processing viral proteins.
• Immature Viral Particles: By inhibiting protease, Pls prevent viral particle maturation, making them non-infectious.
• Disruption of Viral Replication: Disruption of viral protein production halts the overall viral replication cycle.

Mechanism of Action of INSTIs

• Integrase Inhibition: INSTIs target HIV integrase, responsible for inserting the viral genome into the host cell DNA.
• Blocking Integration: INSTIs prevent the integration of viral DNA into the host genome.
• Preventing Proviral Formation: Prevents the formation of latent proviral reservoirs.

Combination Antiretroviral Therapy

• Synergistic Effects: Using multiple drugs with different mechanisms enhances viral suppression.
• Delayed Resistance: Combination therapy makes it harder for the virus to develop resistance.
• Improved Outcomes: Leads to significant improvements in managing HIV/AIDS, reducing morbidity and mortality.

Adverse Effects and Drug Interactions

• Metabolic Complications: Antiretrovirals can cause metabolic changes like lipodystrophy, dyslipidemia, and insulin resistance.
• Hepatotoxicity: Certain drugs can cause liver damage, requiring close monitoring.
• Drug Interactions: Careful consideration of potential side effects and dose adjustments are needed when combining antiretroviral drugs with other medications.