capsid inhibitor for HIV-1 treatment and prevention

Q: How do capsid inhibitors work in HIV?

Answer: It disrupts HIV capsid protein functions

Lenacapavir is the capsid inhibitor approved by the FDA in 2022. It has a unique mechanism of action that disrupts HIV capsid protein functions and impacts key protein-protein interactions necessary for viral entry and virion assembly.

It is very effective in patients with multidrug-resistant HIV, as well as in preventing HIV infection. It is administered in combination with an optimized background ART regimen. 

The beauty of this drug is that after an initial induction regimen that includes oral lenacapavir, it is given only every six months as a subcutaneous injection, thereby improving adherence, particularly in resource-limited countries.

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References:

1. Prather C, Lee A, Yen C. Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Am J Health Syst Pharm. 2023 Dec 5;80(24):1774-1780. doi: 10.1093/ajhp/zxad223. PMID: 37767713.

2. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. N Engl J Med 2022; 386:1793.

3. De Clercq E, Zhang Y, Li G, Deng Y, Khouri R, Růžek D, Król E, Tan L. Lenacapavir: A capsid inhibitor for HIV-1 treatment and prevention. Biochem Pharmacol. 2025 Oct;240:117125. doi: 10.1016/j.bcp.2025.117125. Epub 2025 Jul 5. PMID: 40623458.