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Use of Toll-like receptor 7 (TLR7) agonists to treat the SIV latent reservoir in infected macaques

October 09, 2018

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The authors were interested in the ability of the oral selective Toll-like receptor 7 (TLR7) agonists GS-986 and GS-9620 to induce a transient viraemia in rhesus macaques infected with SIV and treated with suppressive ART, in order to tackle the latent reservoir. They performed an initial dose-escalation study followed by a dose-optimisation study and found that TLR7 agonists can activate multiple innate and adaptive immune cell populations and induce the expression of SIV RNA. The authors also detected TLR7 agonist-induced reductions in both SIV DNA and measured inducible virus from treated animals in ex vivo cell cultures. In a second study they stopped ART and found that two of nine treated animals remained aviraemic for more than 2 years, even after in vivo CD8+ T cell depletion. Adoptive transfer of cells from these aviraemic animals did not induce de novo infection in naïve recipient macaques. Therefore it appears that TLR7 agonists can enable the reduction of the viral reservoir in a subset of SIV-infected rhesus macaques.

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Lim SY, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, et al. ISSN: Sci Transl Med; 10(439): pii: eaao4521

2018

Added: October 09, 2018