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The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.
Author Information (click to view)

Laforge M, Silvestre R, Rodrigues V, Garibal J, Campillo-Gimenez L, Mouhamad S, Monceaux V, Cumont MC, Rabezanahary H, Pruvost A, Cordeiro-da-Silva A, Hurtrel B, Silvestri G, Senik A, Estaquier J,


Laforge M, Silvestre R, Rodrigues V, Garibal J, Campillo-Gimenez L, Mouhamad S, Monceaux V, Cumont MC, Rabezanahary H, Pruvost A, Cordeiro-da-Silva A, Hurtrel B, Silvestri G, Senik A, Estaquier J, (click to view)

Laforge M, Silvestre R, Rodrigues V, Garibal J, Campillo-Gimenez L, Mouhamad S, Monceaux V, Cumont MC, Rabezanahary H, Pruvost A, Cordeiro-da-Silva A, Hurtrel B, Silvestri G, Senik A, Estaquier J,

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The Journal of clinical investigation 2018 03 19128(4) 1627-1640 doi 10.1172/JCI95127

Abstract

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH-treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.

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