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Sci Adv. 2019 Mar 27;5(3):eaav6322. doi: 10.1126/sciadv.aav6322. eCollection 2019 Mar.

Hybrid nanocarriers incorporating mechanistically distinct drugs for lymphatic CD4+ T cell activation and HIV-1 latency reversal.

Author information

1
Department of Bioengineering, University of Washington, Seattle, WA, USA.
2
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
5
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
6
Department of Medicine, University of Washington, Seattle, WA, USA.

Abstract

A proposed strategy to cure HIV uses latency-reversing agents (LRAs) to reactivate latent proviruses for purging HIV reservoirs. A variety of LRAs have been identified, but none has yet proven effective in reducing the reservoir size in vivo. Nanocarriers could address some major challenges by improving drug solubility and safety, providing sustained drug release, and simultaneously delivering multiple drugs to target tissues and cells. Here, we formulated hybrid nanocarriers that incorporate physicochemically diverse LRAs and target lymphatic CD4+ T cells. We identified one LRA combination that displayed synergistic latency reversal and low cytotoxicity in a cell model of HIV and in CD4+ T cells from virologically suppressed patients. Furthermore, our targeted nanocarriers selectively activated CD4+ T cells in nonhuman primate peripheral blood mononuclear cells as well as in murine lymph nodes, and substantially reduced local toxicity. This nanocarrier platform may enable new solutions for delivering anti-HIV agents for an HIV cure.

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