Lenacapavir: A capsid inhibitor for HIV-1 treatment and prevention

Erik De Clercq; Yuya Zhang; Guangdi Li; Yelin Deng; Ricardo Khouri; Daniel Růžek; Ewelina Król; Li Tan

doi:10.1016/j.bcp.2025.117125

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.

Authors

Erik De Clercq¹, Yuya Zhang², Guangdi Li², Yelin Deng³, Ricardo Khouri⁴, Daniel Růžek⁵, Ewelina Król⁶, Li Tan⁷

Affiliations

¹ Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, China; Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
² Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, China.
³ Department of Civil and Environmental Engineering, Soochow University, Suzhou, China.
⁴ Universidade Federal da Bahia, Faculdade de Medicina, Salvador, Bahia, Brazil; Fundação Oswaldo Cruz, Instituto Gonçalo Muniz, Laboratório de Medicina e Saúde Pública de Precisão, Salvador, Bahia, Brazil.
⁵ Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Republic; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Brno, Czech Republic.
⁶ Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
⁷ Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Hunan Clinical Molecular Diagnosis Center, Hunan Engineering Research Center of Molecular Diagnosis Technology, Hunan Clinical Medical Research Center of Molecular Diagnosis of Infectious Diseases, Changsha, China. Electronic address: tanli@csu.edu.cn.

PMID: 40623458
DOI: 10.1016/j.bcp.2025.117125

Abstract

Lenacapavir (GS-6207) is a capsid inhibitor approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced people with multidrug-resistant HIV-1. Here, this study provides a comprehensive overview of lenacapavir, with a particular focus on its long-acting properties, pharmacodynamics, pharmacokinetics, clinical efficacy and safety, and resistance profile. Clinical trials have demonstrated that long-acting lenacapavir is highly effective not only for treating HIV-1 infection but also as a pre-exposure prophylactic agent. The future development of fixed-dose, long-acting combination regimens incorporating lenacapavir and other long-acting antiretroviral agents offers significant potential for durable and effective HIV-1 management in clinical settings.

Keywords: Drug combination; Drug resistance; HIV-1 therapy; Lenacapavir; Pre-exposure prophylaxis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Acetamides
Animals
Anti-HIV Agents* / pharmacokinetics
Anti-HIV Agents* / pharmacology
Anti-HIV Agents* / therapeutic use
Capsid* / drug effects
Capsid* / metabolism
HIV Infections* / drug therapy
HIV Infections* / metabolism
HIV Infections* / prevention & control
HIV-1* / drug effects
HIV-1* / metabolism
Humans
Indazoles

Substances

Anti-HIV Agents
lenacapavir
Acetamides
Indazoles