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Clinical Trial
. 2025 Jun 1;99(2):185-194.
doi: 10.1097/QAI.0000000000003648.

Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial

Joseph C Gathe  1 , Edwin Dejesus  2 , Moti N Ramgopal  3 , Charlotte-Paige Rolle  2 , Otto O Yang  4 , William E Sanchez  5 , Jacob P Lalezari  6   7 , Alok Krishen  7 , Jonah B Sacha  8 , Scott G Hansen  8 , Joseph Meidling  7
Affiliations
Clinical Trial

Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial

Joseph C Gathe et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Leronlimab is a humanized κ-IgG4 monoclonal antibody that blocks C-C chemokine receptor type 5. We investigated leronlimab as a treatment option for people living with multidrug-resistant HIV-1.

Setting and methods: In a phase 2b/3, multicenter, randomized, double-blind, placebo-controlled study conducted in 21 hospital centers in the United States, treatment-experienced people living with HIV with documented drug resistance were randomly assigned once weekly leronlimab (350 mg subcutaneously) or matching placebo for 1 week overlapping existing failing antiretroviral therapy, followed by a 24-week single-arm extension with weekly leronlimab combined with a new optimized background treatment. The primary end point was achieving ≥0.5 log 10 reduction in plasma HIV-1 RNA from baseline at the end of the 1-week double-blinded treatment period.

Results: Fifty-two participants were enrolled (25 leronlimab and 27 placebo). After the 1-week randomized phase, by the intent-to-treat analysis, 64.0% (16/25) receiving leronlimab achieved ≥0.5 log 10 reduction in plasma HIV-1 RNA versus 23.1% (6/26) receiving placebo ( P = 0.0032), whereas by per protocol analysis, 72.7% (16/22) receiving leronlimab achieved ≥0.5 log 10 reduction in plasma HIV-1 RNA versus 24.0% (6/25) receiving placebo ( P = 0.0008). Leronlimab was generally well tolerated with no drug-related serious adverse events reported. Overall, 175 adverse events were reported by 34/52 participants, with 120 (68.6%) adverse events categorized as mild.

Conclusions: Leronlimab resulted in significantly reduced plasma HIV-1 within 1 week after addition to failing antiretroviral therapy. After 24 weeks combined with an optimized background treatment, most participants had plasma HIV-1 RNA levels <50 copies per milliliter plasma, suggesting utility of leronlimab as a component of salvage therapy.

Trial registration: ClinicalTrials.gov NCT02483078.

Keywords: CCR5; HIV; antiretroviral therapy.

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Conflict of interest statement

J.C.G. reports no conflicts of interest. C.-P.R. reports grants and honoraria from ViiV Healthcare and Gilead Sciences. M.N.R. reports honoraria from Abbvie, Gilead Sciences, ViiV Healthcare, and Janssen. E.D. reports funding from ViiV Healthcare, Gilead Sciences, Merck, Abbvie, and Teratechnologies/Taimed. J.B.S. and O.O.Y. have received compensation for serving on the scientific advisory board of CytoDyn. J.B.S., O.O.Y., and S.G.H. have also received compensation for consulting for CytoDyn. This potential conflict of interest (J.B.S. and S.G.H.) has been reviewed and managed by the Oregon Health & Science University. A.K., J.P.L., and J.M. hold stock and are employees of CytoDyn, the manufacturer of leronlimab.

References

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    1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services; 2019. Available at: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Ad... . Accessed April 19, 2021.
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