Pharmacology - HIV antiretroviral drugs (classes, mechanism of action and side effects)

Summary

This video covers the treatment of HIV using antiretroviral therapy (ART). It explains the HIV life cycle and how various antiretroviral drugs target different stages, such as attachment, fusion, reverse transcription, integration, and protease activity. Key drug classes include reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. The video also touches on side effects, combination therapy, and managing opportunistic infections in HIV patients, as well as important considerations like immune reconstitution syndrome (IRIS) when starting ART.

Takeaways

• 🧬 Antiretrovirals are crucial for treating HIV by targeting various stages of the viral life cycle.
• 💊 All patients with HIV should start antiretroviral therapy as soon as they're ready, regardless of their CD4 T cell count.
• 🔗 HIV attaches to CD4 T cells via gp120 and co-receptors CCR5 and CXCR4, allowing viral fusion and entry into the cell.
• 🧪 Reverse transcription is the process by which HIV converts its RNA into DNA using reverse transcriptase.
• 🧬 Integrase allows the integration of HIV DNA into the host's DNA, making the virus part of the host cell.
• 🧫 Nucleoside and nucleotide reverse transcriptase inhibitors block the creation of viral DNA by mimicking nucleotides.
• 💉 Protease inhibitors prevent the maturation of new HIV viruses, leading to non-infectious viral particles.
• 🦠 Fusion inhibitors, like enfuvirtide, prevent the fusion of the HIV envelope with the host cell membrane.
• 🧬 Non-nucleoside reverse transcriptase inhibitors directly inhibit reverse transcriptase by binding to it.
• 💉 Immune reconstitution syndrome (IRIS) can occur after starting antiretroviral therapy, as the immune system rebounds and attacks latent infections.

Q & A

What is the role of antiretroviral therapy in treating HIV patients?

Antiretroviral therapy (ART) is essential in treating HIV patients by targeting different stages of the viral life cycle, preventing the virus from replicating and thus slowing the progression of HIV.

Why should all HIV patients begin antiretroviral therapy, regardless of CD4 T cell count?

All HIV patients should start antiretroviral therapy as soon as they are ready because it helps control the virus, prevents disease progression, and reduces the risk of transmission, regardless of their CD4 T cell count.

How does HIV infect CD4 T cells?

HIV targets CD4 T cells by binding its glycoprotein gp120 to CD4 receptors, along with co-receptors CCR5 and CXCR4, allowing the virus to fuse with the cell membrane and release its viral contents into the host cell.

What is the significance of reverse transcription in the HIV life cycle?

Reverse transcription is crucial because it allows the virus to convert its RNA into DNA using the enzyme reverse transcriptase, enabling integration into the host cell's DNA and initiating viral replication.

How do reverse transcriptase inhibitors block HIV replication?

Reverse transcriptase inhibitors block HIV replication by preventing the enzyme reverse transcriptase from creating viral DNA. They either mimic nucleotides or bind directly to the enzyme, terminating the DNA chain and stopping viral replication.

What is the function of integrase in the HIV life cycle, and how do integrase inhibitors work?

Integrase is an enzyme that helps integrate viral DNA into the host cell's DNA. Integrase inhibitors prevent this process, stopping the virus from using the host's genetic machinery to replicate itself.

What are some adverse effects of the protease inhibitors used in HIV treatment?

Protease inhibitors can cause side effects such as nausea, diarrhea, hyperlipidemia, and insulin resistance. Some specific inhibitors, like atazanavir, may also cause hyperlipidemia and issues with absorption if the patient is using proton pump inhibitors (PPI).

Why is prophylaxis important for HIV patients, and what are common prophylactic treatments?

Prophylaxis is important for preventing opportunistic infections in HIV patients, especially when their CD4 T cell count is low. Common prophylactics include Bactrim for preventing PJP and toxoplasmosis, and azithromycin (historically) for preventing Mycobacterium avium complex.

What is immune reconstitution syndrome (IRIS) in the context of HIV treatment?

Immune reconstitution syndrome (IRIS) occurs when a patient starts antiretroviral therapy, and their recovering immune system begins to attack existing infections in the body, leading to an inflammatory response and worsening symptoms of those infections.

Why are live vaccines generally not recommended for HIV patients with low CD4 counts?

Live vaccines are usually avoided in HIV patients with CD4 counts below 200 cells/mm³ because their weakened immune systems may not handle the live virus in the vaccine, potentially leading to infections.