How Do Capsid Inhibitors Work?

Capsid inhibitors belong to a novel, first-in-class drug approved by the FDA on December 22, 2022 for use as a part of the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Currently, lenacapavir is the first and only drug to be approved by the FDA in this class of medications. Capsid inhibitors prevent HIV replication by binding to capsid, the protein that encases the viral genetic material. 

HIV-1 infection is caused by a virus that infects immune cells known as T-cells. HIV infection is transmitted through body fluids such as blood, semen, vaginal fluids or breastmilk. In its later stages, HIV infection can lead to acquired immune deficiency syndrome (AIDS) when the immune system is so weakened it is unable to fight even common infections.

The virus fuses with the immune cell, incorporates itself into its DNA and uses the cell machinery to replicate itself, destroying the host cell in the process. The capsid protein shell of the virus plays important roles in the interaction between the virus and the host cell. By inhibiting capsid protein, capsid inhibitors interfere with a number of essential steps in the viral lifecycle.

Capsid inhibitors interfere with HIV replication in the following ways:

• Prevent capsid from binding to nuclear import proteins and transporting the viral DNA into the host cell nucleus
• Reduce production of capsid protein subunits required for the assembly and release of new viral particles into the bloodstream to infect other cells
• Reduce capsid core formation by disrupting the rate of capsid subunit association, which results in malformed capsids 

Capsid inhibitors are approved by the FDA for the treatment of HIV-1 infection, in combination with other antiretrovirals, in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. Capsid inhibitors are administered as oral tablets or as subcutaneous injections.

Side effects of capsid inhibitors may include the following:

• Injection site reactions including:
• Discomfort and pain
• Redness (erythema)
• Blood clot under the skin (hematoma)
• Tissue hardening (induration)
• Nodule
• Fluid collection and swelling (edema)
• Itching (pruritus)
• Residual mass
• Ulcer
• Increase in serum creatinine
• High glucose levels in the blood (hyperglycemia)
• Excessive sugar excretion in the urine (glycosuria)
• Excessive protein in the urine (proteinuria)
• Nausea
• Increase in direct serum bilirubin
• Increase in liver enzymes:
• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of capsid inhibitors include:

• lenacapavir
• Sunlenca
• Yeztugo