ACTG launches Phase 2 trial of dasatinib to shrink HIV reservoir
ACTG, the NIH-funded clinical trials network, has opened enrolment in A5413, a randomised, double-blind, placebo-controlled study evaluating whether oral dasatinib can reduce the HIV reservoir in virally suppressed adults receiving antiretroviral therapy (ART).
The study will enrol 14 participants aged 18 and over who have been on continuous ART for at least four years and virally suppressed for at least three. Eight will receive 100 mg of dasatinib daily for 12 weeks; six will receive matched placebo. All participants will then be followed for a further 24 weeks. The primary focus is safety, tolerability, and measurable impact on reservoir size.
The science behind A5413
Dasatinib is a tyrosine kinase inhibitor already approved for leukaemia, where its ability to block cellular proliferation — the process by which T-cells divide and replicate — is a clinical asset. The hypothesis underpinning A5413 is that this same property could prevent CD4 cells harbouring latent HIV from multiplying, thereby gradually reducing the size of the reservoir rather than attempting to flush it out through viral reactivation.
Adam Spivak, Study Chair at the University of Utah School of Medicine, said dasatinib "has been shown to block the process by which T-cells divide and multiply" and that the trial "will hopefully provide insights more broadly into the role of cellular proliferation on HIV persistence." The approach is mechanistically distinct from so-called "shock and kill" strategies, which aim to reactivate dormant virus so that immune clearance or ART can eliminate infected cells — an area that has seen mixed results in prior studies.
A5413 is the first study to enrol participants under ACTG's Small Clinical Trials Advancing HIV Remission and Cure programme, a pathway designed to support intensive, small-scale experimental trials using existing ACTG infrastructure and specialist laboratories.
Market context and competitive landscape
HIV cure research has attracted sustained investment from both public funders and private biotechs, though progress has been slow. Broadly neutralising antibodies, long-acting ART formulations, and gene-editing approaches — including CRISPR-based excision strategies — are among the parallel tracks under investigation by academic groups, companies such as Gilead Sciences and ViiV Healthcare, and a number of university spinouts. Most clinical-stage cure candidates remain in early proof-of-concept work, reflecting the deep scientific complexity of eliminating a reservoir that establishes itself within days of primary infection.
The drug-repurposing angle in A5413 is relatively low-cost and fast to execute compared with novel biologic approaches, and NIAID's willingness to fund the study under award numbers covering ACTG's broader network suggests institutional confidence in the proliferation-inhibition hypothesis. However, the 14-participant cohort means A5413 is powered for mechanistic insight rather than efficacy conclusions; any reservoir reduction signal would need replication in a larger study before informing a late-stage programme.
ACTG Chair Joseph Eron said the trial "adds to our robust portfolio of clinical trials in this space" and is expected to deepen understanding of reservoir dynamics. The study is co-sponsored by the National Institute of Mental Health and NIAID, reflecting growing recognition of the neurological comorbidities associated with long-term HIV persistence even under viral suppression.
Topline data from the 12-week treatment period and 24-week follow-up are not yet scheduled for public release; investigators are expected to present findings at an infectious disease conference following study completion.