%0 Journal Article
%T The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques
%A Alain Pruvost
%A Anabela Cordeiro-da-Silva
%A Anna Senik
%A Bruno Hurtrel
%A Guido Silvestri
%A Henintsoa Rabezanahary
%A Julie Garibal
%A J¨¦r£¿me Estaquier
%A Laure Campillo-Gimenez
%A Marie-Christine Cumont
%A Mireille Laforge
%A Ricardo Silvestre
%A Shahul Mouhamad
%A Val¨¦rie Monceaux
%A Vasco Rodrigues
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI95127
%X 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¨Ctreated 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
%U https://www.jci.org/articles/view/95127