Comment from Gillian McCrea
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Summary: The commenter proposes the repurposing of Leronlimab (an HIV-derived CCR5 antibody) for the treatment of Long COVID. They argue that the drug targets a specific inflammatory axis and suggest the FDA consider a biomarker-gated Phase 2 trial based on existing exploratory data.
Leronlimab (Anti-CCR5) for Long COVID
An HIV-derived CCR5 antibody for a biomarker-defined subset | For FDA repurposing / advisory review
The opportunity
The HIV reservoir-and-monocyte paradigm maps onto Long COVID, where persistent spike-bearing CD16+ monocytes drive vascular inflammation through the CCR5 axis. Leronlimab targets exactly that receptor.
The mechanism
Leronlimab (PRO 140) is a CCR5-binding monoclonal antibody that disrupts the CCL5/RANTES–CCR5 axis, reducing the monocyte-driven inflammation implicated in Long COVID [1].
A responder biomarker already exists
In an exploratory randomized Long COVID trial (UCLA, Yang; ~55 patients), symptomatic responders were identified by a CCR5 biomarker — patients starting with low T-cell CCR5 improved, revealing a treatable immune-downmodulation subset [2]. A new Phase 2 long-hauler trial (102 patients, 10 sites) has been filed with the FDA [3]. Leronlimab carries an extensive HIV-derived safety record.
The ask
A biomarker-gated Phase 2 in low-CCR5 Long COVID — an HIV antiviral with a validated mechanism and an actual responder biomarker already in hand.
Sources
1. Leronlimab (PRO 140, anti-CCR5) exploratory Long COVID trial, UCLA (Yang): responder biomarker (baseline CCR5). Clin Infect Dis. 2022. NCT04678830.
2. New Phase 2 leronlimab long-hauler trial (102 patients, 10 sites) filed with FDA, 2026.
3. Leronlimab CCL5/RANTES–CCR5 mechanism; HIV development program (CytoDyn).