ACTG has opened enrollment for A5426 (IPACE-HIV), a Phase 2, double-blind, randomized study testing the senolytic combination of dasatinib and quercetin against placebo for 12 weeks, with an additional 12-week follow-up to assess durability. The 80-participant, multicenter trial targets people living with HIV aged 50 and older who are virally suppressed on ART, were diagnosed at least 10 years ago, meet at least one Fried frailty criterion, and demonstrate slowed gait on a four-meter walk. The study’s primary focus is safety, tolerability, and improvement in physical function.
The move formalizes a geroscience hypothesis within an HIV-experienced population that experiences frailty and functional decline earlier than the general population, despite virologic control. With current management largely limited to exercise, nutrition, and comorbidity optimization, the study is designed to test whether clearing senescent cells can shift underlying biology rather than layer on another symptomatic intervention. It is the first rigorously controlled evaluation of senolytics for frailty in people living with HIV, funded by NIA and NIAID within the ACTG network, signaling institutional interest in pharmacologic options for age-associated morbidity in HIV.
Operationally, the design prioritizes measurable, clinic-friendly functional endpoints and short treatment exposure. Standardized four-meter walk assessments and frailty phenotyping will require sites to deploy geriatric assessment workflows alongside routine HIV care, an increasingly common need as aging-focused protocols enter infectious disease portfolios. Randomization and a defined follow-up window should help isolate signal and capture durability while limiting prolonged exposure to dasatinib, a TKI with known hematologic and cardiopulmonary risks. Sites will need to manage drug–drug interaction vigilance, particularly with boosted regimens, and ensure consistent implementation of functional tests across centers to prevent measurement drift. Recruitment feasibility appears favorable given the sizable pool of virologically suppressed older adults, but the added requirement of slow gait and at least one frailty criterion will narrow eligibility and may slow screening-to-randomization conversions.
Strategically, this is a boundary test for repurposing oncology pharmacology in a high-comorbidity HIV cohort. The bet is that a short-course senolytic approach can deliver clinically relevant gains in mobility and physical performance without compromising hematologic safety or ART tolerability. For CROs and vendors, the trial offers a blueprint for integrating geriatric endpoints into infectious disease studies, with potential roles for centralized training, uniform gait-testing protocols, and digital capture to reduce inter-site variability. For sponsors, a positive readout could validate functional outcomes as decision-grade measures in HIV comorbidity trials and strengthen the case for pragmatic designs that blend clinic visits with remote functional monitoring.
The near-term watchlist is straightforward: recruitment velocity in a frail population, adherence and completion rates over the 12-week dosing period, any early hematologic or cardiopulmonary safety signals, and the magnitude and persistence of changes in gait speed and frailty components at week 24. Subgroup performance by ART backbone and comorbidity burden will matter for generalizability. If efficacy and safety align, the next steps likely include a larger confirmatory study and exploration of combination strategies with structured exercise or rehabilitation. Regulatory pathways for label expansion are uncertain given generic components and a supplement co-therapy, so traction will depend on reproducible functional gains and guideline adoption. Regardless of outcome, IPACE-HIV will help define whether senolytics merit a place in the HIV aging toolbox and will shape how future trials in this space measure and operationalize physical function at scale.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
