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

Area of Science:

• Immunology
• Virology
• Clinical Medicine

Background:

• Leronlimab is a humanized IgG4 monoclonal antibody targeting the CCR5 receptor.
• Investigated as a novel therapeutic for multidrug-resistant HIV-1 infections.

Purpose of the Study:

• To evaluate the efficacy and safety of leronlimab in treatment-experienced HIV-1 patients with documented drug resistance.
• To assess leronlimab's potential as part of a salvage therapy regimen.

Main Methods:

• Phase 2b/3, randomized, double-blind, placebo-controlled trial across 21 US centers.
• Participants received weekly leronlimab or placebo for 1 week, followed by a 24-week extension with leronlimab and optimized background treatment.
• Primary endpoint: ≥0.5 log10 reduction in plasma HIV-1 RNA after 1 week.

Main Results:

• 64% of leronlimab recipients achieved the primary endpoint vs. 23.1% of placebo recipients (P=0.0032) by ITT analysis.
• Per-protocol analysis showed 72.7% vs. 24.0% efficacy (P=0.0008).
• Leronlimab was well-tolerated; no drug-related serious adverse events were reported, with most adverse events being mild.

Conclusions:

• Leronlimab demonstrated significant plasma HIV-1 RNA reduction within one week when added to failing ART.
• After 24 weeks, most participants achieved viral loads <50 copies/mL, indicating leronlimab's utility in salvage therapy.