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Author: Medical Team

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The US Food and Drug Administration (FDA) gave clearance to first in class antiretroviral drug “Lenacapavir” (Sunlenca) for adults with multidrug-resistant HIV-1 infection.

As the mechanism of action is concerned, Lenacapavir being the first-in-class capsid inhibitor acts by preventing viral replication at both the early and late stages of the life cycle by interfering with capsid-mediated nuclear uptake of pre-integration complexes and hindering virion formation. Lenacapavir exhibits antiviral effectiveness against viral variants that are resistant to the majority of existing antiretroviral medication classes.

Due to its picomolar potency, low clearance, and slow release kinetics, Lenacapavir can be given orally or subcutaneously up to every six months in a long-acting manner allowing convenient dosing for patients.

A daily pill containing two or three HIV medications often makes up an HIV drug regimen.

Cabenuva (Cabotegravir/Rilpivirine), which can be taken either monthly or every other month, was the first injectable full medication regimen for HIV-1 infection to receive FDA approval in 2021. Lenacapavir is only administered twice a year, however it is also given in combination with other antiretrovirals.

The regulatory approval was given on the basis of multicenter clinical trial consisting of 72 patients with HIV-1 infection who were multidrug resistant. Patients were distributed in two groups. Double-blind randomization was used to assign one group to receive Lenacapavir or a placebo, while the other group received open-label Lenacapavir.

The percentage of patients in the randomized study group in which a specific level of viral reduction over the first 14 days compared to baseline was seen, served as the major indicator of efficacy.

Lenacapavir was administered to 87.5% of the patients in this group, whereas a placebo was given to 16.7% of the patients. After 26 weeks of taking Lenacapavir together with other antiretrovirals, 81% of the participants in the first group had reached HIV RNA suppression, where levels of HIV were too low to be detected. 83% of subjects still had HIV RNA suppression after the period of 52 weeks.

Injection site reactions and nausea were the common adverse reactions associated with Lenacapavir during the study. There was no documented severe adverse event of Lenacapavir.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, M.D., Director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research. 


  1. FDA approves new HIV drug for adults with limited treatment options, U.S. Food and Drug Administration. FDA. Available at: (Accessed: December 28, 2022).
  2. Segal-Maurer, S., DeJesus, E., Stellbrink, H. J., Castagna, A., Richmond, G. J., Sinclair, G. I., Siripassorn, K., Ruane, P. J., Berhe, M., Wang, H., Margot, N. A., Dvory-Sobol, H., Hyland, R. H., Brainard, D. M., Rhee, M. S., Baeten, J. M., Molina, J. M., & CAPELLA Study Investigators (2022). Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. The New England journal of medicine, 386(19), 1793–1803.
  3. A treatment option: Cabenuva (cabotegravir; Rilpivirine) Long-Acting HIV Treatment | CABENUVA (cabotegravir; rilpivirine). Available at: (Accessed: December 28, 2022).