There are six different types of HIV medications.  These medications operate by targeting certain HIV proteins, such as enzymes for replication found inside the viral particle like reverse transcriptase and protease. Two of the six HIV medications target proteins on the viral or host cell surface instead of inside the host cell, aiming to keep the virus from infecting cells in the first place.  These two types of medications are called entry inhibitors and fusion inhibitors.

Maraviroc, the only FDA approved entry inhibitor, was developed at Pfizer Inc.

Image Source: Bloomberg

Entry inhibitors, as suggested by the name, prevent the HIV virus from entering immune system cells, more specifically, a type of cell called a T cell. To begin infection, HIV must bind to receptor proteins on the surface of the T cell. Entry inhibitors prevent infection by binding to the receptor proteins on the T-cell, thus blocking the binding sites for HIV. Because HIV targets a variety of proteins on the surface of the cell, many types of entry inhibitors are possible. The only FDA approved entry inhibitor, Maraviroc, binds to the CCR5 protein. Because medications acting on the CCR5 protein have been successful, CCR5 is also the target of new, currently developing entry inhibitors. Another potential target is the CXCR4 protein.

Like entry inhibitors, fusion inhibitors prevent HIV from infecting T cells by binding to certain surface proteins. However, fusion inhibitors are different because they target the final stage of HIV infection, called the fusion stage, before HIV enters the cell. Additionally, fusion inhibitors bind to proteins on the viral particle, instead of proteins on the T cell. After binding to the T cell proteins, HIV must attach to the cell and undergo structural changes in order to fuse and enter. Fusion inhibitors prevent infection by binding to the viral protein and blocking the subsequent structural changes. The only FDA approved fusion inhibitor is Enfuvirtide, which binds to the gp41 protein on the HIV virus.

An illustrated depiction of HIV fusing with a cell.

Image Source: MedicalRF.com

Entry inhibitors and fusion inhibitors carry out similar functions. Because of their similarities, they are sometimes placed in the same class of drugs, though they are classified as two different classes by the FDA. Though entry and fusion inhibitors are relatively new in the field of antiretroviral medications, they can be beneficial for patients with more resistant forms of HIV, since the inhibitors target different components of the HIV virus. Because the HIV virus has not yet been exposed to these new drugs, it is less likely to be resistant. However, with many developments still taking place in the field of antiretroviral drugs, it may take time for entry inhibitors and fusion inhibitors to become more common in HIV treatment regimens.

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Dorothy Kenny

Author Dorothy Kenny

Dorothy graduated from UCLA in 2017 with a degree in Microbiology, Immunology, and Molecular Genetics. Her hobbies include creative writing, playing guitar, and listening to excessive amounts of Korean pop music. As a premed student, she relies heavily on the power of procrastination and caffeine for daily function.

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