Post-attachment Inhibitors

Post-attachment inhibitors are a class of drugs used to suppress HIV in the body. When post-attachment inhibitors are used in combination with other HIV-fighting drugs, the treatment regimen is referred to as antiretroviral therapy (ART).¹

HIV needs to enter human host cells called CD4 cells, or T cells, to replicate. To enter into these cells, HIV needs to bind to the host cell surface and then fuse itself with the host cell to get inside. Post-attachment inhibitors block the binding step in the process, preventing HIV from attaching and getting into its target cell to replicate.²

HIV life cycle

Viruses like HIV need human host cells to replicate. They cannot multiply on their own without human cells. When HIV particles called virions enter the body after a transmission event, the next main steps of the HIV lifecycle are as follows:²

1. Binding
2. Fusion
3. Reverse transcription
4. Integration
5. Replication
6. Assembly
7. Budding

Figure 1. Post-attachment inhibitors target binding in the HIV life cycle

The HIV virions have proteins on the outside that recognize receptors on CD4 cells. Once a virion finds a CD4 cell, its outside proteins can bind to the CD4 cell receptor and link the CD4 cell and virion together (step 1: binding). For the virus to fully bind and fuse with the CD4 cell and get inside the cell to continue replication (step 2: fusion), other receptors on the CD4 cell surface may get involved. These additional receptors on the CD4 cell include the CCR5 or CXCR4 receptors. The HIV surface receptors involved in the first two steps are called gp120 and gp41. Any of these receptors on the CD4 cell or HIV itself may be targets for HIV drugs.²

Once inside the cell, the virion disassembles itself so that it can begin the replication process. The next three steps represent the replication process of the virus’s genetic material. The last two steps of the process involve HIV re-assembling itself into new, mature virions that can be released from the CD4 cell and enter the bloodstream where they can go on to infect new cells.²

How do post-attachment inhibitors work?

Post-attachment inhibitors block the CD4 receptor on the outside of CD4 cells. The CD4 receptor is involved in the binding of HIV to its target cell. HIV needs to bind using the CD4 receptor to move on to the next step in the life cycle, fusion, and entry into the cell. When the CD4 receptors are blocked by a post-attachment inhibitor, HIV cannot adequately bind to its target cell. This stops the replication process since HIV needs to get inside the human host cells to replicate.^1,3

Post-attachment inhibitors block the step before fusion. When using a post-attachment inhibitor, an HIV virion can still fuse with a CD4 cell, but time binding to the host cell in the first place.^1,3

Examples of post-attachment inhibitors

Post-attachment inhibitors approved to treat HIV include:^1,3

• Trogarzo^® (ibalizumab-uiyk)

What are the possible side effects?

The most common side effects of Trogarzo include:³

• Diarrhea
• Nausea
• Dizziness
• Rash

These are not all the possible side effects of Trogarzo. Talk to your doctor about what to expect when taking Trogarzo. You also should call your doctor if you have any changes that concern you when taking Trogarzo.

Other things to know

Before starting treatment with Trogarzo, tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding.³

Before beginning treatment for HIV, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.