HIV Entry Inhibitors and Treatments

The sequence of steps that HIV takes to infect and replicate within a host cell.

Treatment using medications that interfere with different stages of the HIV life cycle, preventing the virus from multiplying.

The initial step where HIV attaches to and enters a host cell, facilitated by the interaction of the virus's gp120 protein with the host cell's CD4 receptor.

Antiretroviral drugs that block HIV from attaching to or entering a host cell.

A protein found on the surface of certain immune cells, such as T cells, that HIV gp120 binds to during the entry process.

A protein on the surface of immune cells, alongside CD4, that HIV gp120 binds to for entry.

Antiretroviral drugs that block the fusion of the HIV envelope with the host cell membrane, halting entry.

A drug that prevents HIV from attaching to CD4 receptors, acting as a post-attachment inhibitor.

A medication that blocks HIV from attaching to CD4 cells, preventing the virus from entering the cell. It's a prodrug, meaning it needs to be converted to its active form (temsavir) within the body.

Fostemsavir targets the gp120 subunit of the HIV envelope protein.

Fostemsavir binds to the gp120 subunit of HIV, stopping it from interacting with CD4 receptors on host cells.

Common side effects include nausea, hepatotoxicity (liver damage), and potential renal failure.

Fostemsavir is a substrate of the enzyme CYP3A4.

Inducers of CYP3A4 can speed up the metabolism of Fostemsavir, reducing its effectiveness.

These tests monitor liver (ALT, AST) and kidney (sCr) function, which are potential targets of Fostemsavir's side effects.

Fostemsavir is a prodrug, converted to temsavir. Temsavir binds to the gp120 subunit of the HIV envelope protein, preventing the virus from attaching to CD4 receptors on host cells.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are a type of antiretroviral drug that blocks the activity of the HIV enzyme reverse transcriptase, preventing the conversion of HIV RNA into DNA.

NRTIs are chemically modified versions of normal nucleotides. Once inside the cell, they get converted into their active form, which then competes with normal nucleotides needed for HIV DNA production. NRTIs, lacking a crucial 3’-hydroxyl group, block further DNA synthesis, preventing the HIV virus from making copies of itself.

Reverse transcriptase is an enzyme used by HIV to convert its RNA into DNA. This DNA is then integrated into the host cell's DNA.

Zidovudine is an NRTI that is a thymidine analog. It's a commonly used drug in HIV treatment regimens.

Abacavir is an NRTI that is a thymidine analog. It's effective against HIV and is used in combination with other antiretrovirals.

Lamivudine is an NRTI that is a cytidine analog. It's used to treat HIV infection.

Emtricitabine is an NRTI that is a cytidine analog. Commonly used in combination with other antivirals in HIV treatment.

Tenofovir is an NRTI that is an adenine analog, also known as a nucleotide reverse transcriptase inhibitor. It is a pre-phosphorylated drug, meaning it's already partially activated before entering the cell.

Prodrugs of tenofovir (TFV) used to treat HIV. Both are converted to tenofovir within the body, but TAF has lower bone and kidney side effects due to different intracellular phosphorylation.

A prodrug of tenofovir (TFV) that is hydrolyzed to TFV in the plasma and then phosphorylated intracellularly in HIV-infected cells. It is commonly used in HIV treatment but has significant bone and kidney side effects.

A prodrug of tenofovir (TFV) that is both hydrolyzed and phosphorylated intracellularly in HIV-infected cells. TAF has a lower risk of bone and kidney problems compared to TDF.

A class of antiretroviral drugs used to treat HIV. They work by inhibiting the enzyme reverse transcriptase, preventing the virus from replicating.

A combination drug containing emtricitabine and tenofovir disoproxil fumarate (TDF). It is a common first-line treatment for HIV, but has the potential for bone and kidney issues due to TDF.

A combination drug containing emtricitabine and tenofovir alafenamide (TAF). Preferred over Truvada because TAF has fewer side effects on bones and kidneys.

A combination drug containing lamivudine and tenofovir disoproxil fumarate (TDF) used to treat HIV.

A combination drug containing lamivudine and abacavir used to treat HIV.

HIV integrase is an enzyme that helps insert HIV DNA into the host cell's DNA. This is crucial for the virus to replicate and spread.

INSTIs are medications that block the integrase enzyme from inserting HIV DNA into the host cell's DNA, effectively stopping the virus from replicating.

When INSTIs block integrase, the HIV DNA cannot integrate into the host cell's DNA. This typically leads to the HIV DNA being degraded by the host cell's repair enzymes.

The HIV integrase enzyme binds to each end of the newly formed HIV DNA.

The integrase enzyme binds to the ends of the newly formed HIV DNA and then inserts it into the host cell's DNA.

The integrase enzyme is responsible for inserting the newly formed HIV DNA into the host cell's DNA. This is essential for the virus to replicate and spread.

The integrase enzyme is crucial for HIV replication because it allows the virus to integrate its DNA into the host cell's DNA. Blocking this enzyme effectively prevents the virus from spreading.

HIV develops resistance to protease inhibitors through mutations in the enzyme's active site and other regions, making these drugs less effective. These mutations can arise in the active site of the protease or in distant regions of the protein.

Lenacapavir is an HIV capsid inhibitor that works by binding to the gp-24 subunit of the HIV capsid, disrupting the transport of the capsid core through the nuclear pore complex, preventing uncoating, and inhibiting reassembly of the capsid.

The HIV capsid is a protein shell that encloses the viral genome (HIVRNA), reverse transcriptase, and integrase. It protects the viral genetic material and facilitates its journey within the host cell.

Lenacapavir prevents the HIV capsid from assembling properly, blocking its ability to enter the host cell nucleus and replicate. It essentially locks the capsid in a state where it can't function, preventing the spread of the virus.

Lenacapavir binds to the gp-24 subunit of the HIV capsid, disrupting its transportation through the nuclear pore, which is crucial for the virus to replicate. It also blocks the capsid from uncoating, which prevents the virus from releasing its genetic material.

Lenacapavir is typically used as a second-line option for treating HIV infection in patients who have developed resistance to other antiretroviral therapies, such as Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

Lenacapavir can be administered subcutaneously (under the skin) because it is designed to release slowly over a longer period, reducing the frequency of injections compared to traditional oral medications.

Lenacapavir is a long-acting drug with a convenient subcutaneous administration schedule. It is a promising treatment option for people with HIV, especially those who have developed resistance to conventional antiretroviral therapies.