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Clinical Trial
. 2025 Mar 17;80(3):566-574.
doi: 10.1093/cid/ciae423.

Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir in Heavily Treatment-Experienced People with Multidrug-Resistant HIV-1: Week 104 Results of a Phase 2/3 Trial

Onyema Ogbuagu  1 , Jean-Michel Molina  2   3   4 , Ploenchan Chetchotisakd  5 , Moti N Ramgopal  6 , William Sanchez  7 , Jason Brunetta  8 , Francesco Castelli  9 , Gordon E Crofoot  10 , Chien-Ching Hung  11   12   13 , Sylvie Ronot-Bregigeon  14 , Nicolas A Margot  15 , Hui Wang  15 , Hadas Dvory-Sobol  15 , Martin S Rhee  15 , Sorana Segal-Maurer  16
Affiliations
Clinical Trial

Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir in Heavily Treatment-Experienced People with Multidrug-Resistant HIV-1: Week 104 Results of a Phase 2/3 Trial

Onyema Ogbuagu et al. Clin Infect Dis. .

Abstract

Background: Lenacapavir is a long-acting human immunodeficiency virus type 1 (HIV-1) capsid inhibitor for treatment of HIV-1 infection. We evaluated the efficacy and safety of lenacapavir in combination with an investigator-selected optimized background regimen (OBR) after 104 weeks in adults with multidrug-resistant HIV-1.

Methods: This ongoing, international, Phase 2/3 trial at 42 sites included 72 adults with multidrug-resistant HIV-1. Following a 2-week oral lenacapavir loading phase, participants received subcutaneous lenacapavir every 26 weeks with an OBR. HIV-1 RNA, CD4 cell counts, and adverse events were assessed over 104 weeks. One participant did not enter the extension phase.

Results: At Week 104, 44 of 71 participants (62%, 95% confidence interval [CI]: 50; 73) had HIV-1 RNA <50 copies/mL via US Food and Drug Administration (FDA) snapshot algorithm. When missing data (including discontinuations) were excluded, 44 of 54 participants (82%) had HIV-1 RNA <50 copies/mL at Week 104, mean CD4 cell count increased by 122 cells/µL (95% CI: 80; 165), and the proportion of participants with CD4 cell count <200 cells/µL decreased from 64% (46 of 72) at Baseline to 29% (16 of 55). Fourteen participants had treatment-emergent lenacapavir resistance; 7 resuppressed (HIV-1 RNA <50 copies/mL) while maintaining lenacapavir use. There were no Grade 4 or serious treatment-related adverse events. One participant discontinued study drug due to an injection site reaction.

Conclusions: Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks. Lenacapavir represents an important treatment option in people with multidrug-resistant HIV-1.

Trial registration: ClinicalTrials.gov NCT04150068.

Keywords: HIV-1; capsid inhibitor; heavily treatment-experienced; lenacapavir; subcutaneous.

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Conflict of interest statement

Potential conflicts of interest . O. O. has served as an advisor/consultant to Gilead Sciences, Inc., ViiV, and Janssen, and has received honoraria from Gilead Sciences, Inc. J. M. M. has served as an advisor/consultant to Gilead Sciences, Inc., ViiV, and Merck, and has received research support from Gilead Sciences, Inc. P. C. has received research support from Gilead Sciences, Inc. M. N. R. has served as an advisor/consultant to Gilead Sciences, Inc., ViiV, MSD, and Abbott, has received research support from Gilead Sciences, Inc., and has received honoraria from Gilead Sciences, Inc., ViiV, and AbbVie Inc. W. S. has served as an advisor/consultant to Gilead Sciences, Inc., and Merck, and has received research support from GSK and Merck. J. B. has served as an advisor/consultant to Gilead Sciences, Inc., Canada, and ViiV, and has received honoraria from Gilead Sciences, Inc., Canada. F. C. is acting as principal investigator of various therapeutical clinical trials concerning HIV without any personal financial benefit. G. E. C. has received research support from Gilead Sciences, Inc., ViiV, Janssen, Merck, and AbbVie, Inc. C. C. H. has received research support and honoraria from Gilead Sciences, Inc., Canada. N. A. M., H. W., H. D. S., and M. S. R. have served as employees and shareholders of Gilead Sciences, Inc. S. S.-M.: at the time of study conduct, data analysis, and manuscript preparation, S. S.-M. had served as an advisor/consultant to Gilead Sciences, Inc., Janssen, ViiV, and Theratechnologies, and received research support and honoraria from Gilead Sciences, Inc; S. S.-M. is now an employee and shareholder of Gilead Sciences, Inc. All other authors report no potential conflicts The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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