Introduction: Combined antiretroviral therapy (cART) has revolutionised the treatment of human immunodeficiency virus type 1 (HIV-1) infection. However, a subset of patients infected with multidrug-resistant viruses (HIV-MDR) faces a high risk of morbidity and mortality. The search for therapies that overcome these resistance profiles has become a priority. In this scenario, lenacapavir (GS-6207) emerges as a first-line agent. It is the first inhibitor of the viral capsid proteins, blocking both assembly and disassembly – a mechanism not previously exploited by existing drugs.
Objective: To analyse the scientific evidence on the use of lenacapavir, focusing on its efficacy in controlling viral replication, safety, and management in adults with HIV-MDR infection.
Methods: A narrative review of the scientific literature was conducted by searching the PubMed/MEDLINE and Embase databases. A total of 187 articles published between 2020 and 2025 were identified; after removal of duplicates and articles meeting the exclusion criteria, 10 original articles were selected as the analytical basis for this synthesis.
Results: Lenacapavir, administered subcutaneously every six months, demonstrated potent antiretroviral activity in hard-to-treat viral populations. The pivotal CAPELLA trial (phase 2/3) showed that 81% of patients with multidrug-resistant infections who received lenacapavir plus an optimised background regimen (OBR) achieved suppressed viral load (<50 copies/mL), contrasting with those receiving placebo/OBR. This success was sustained long-term (52 weeks), confirming the durability of the response. The mechanism of action proved effective even against viruses resistant to all other antiretroviral classes. The safety profile was favourable. Cases of resistance were observed, underscoring the importance of combined use with other agents. Pharmacokinetic studies confirmed stable plasma concentrations over six months, supporting the six-month dosing paradigm.
Conclusion: Lenacapavir can be considered a transformative therapeutic advance in the treatment of HIV infection. It ushers in a new era in antiretroviral therapy, offering not only a rescue option but also a new paradigm of convenience and potential adherence.
Biography :
Letizia Pires Marchelli is an academic affiliated with Universidade Nove de Julho (Uni9), Brazil. She is dedicated to advancing research and academic excellence within her field, contributing to the development of innovative ideas and scholarly knowledge. Her work reflects a strong commitment to collaboration, interdisciplinary approaches, and continuous learning. Letizia actively participates in academic initiatives, including conferences and research projects, where she engages with global experts and shares her insights. She is passionate about fostering intellectual growth and supporting the academic community through her research contributions, professional engagement, and commitment to high-quality education and scientific progress.
