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

J Clin Invest. 2018 Apr 2;128(4):1627-1640. doi: 10.1172/JCI95127. Epub 2018 Mar 19.


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.

Keywords: AIDS/HIV; Apoptosis; Apoptosis inhibitors; Immunology; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / enzymology
  • Acquired Immunodeficiency Syndrome / pathology
  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Animals
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / pathology
  • Caspase Inhibitors / pharmacology*
  • Disease Progression
  • Female
  • Lymphocyte Depletion
  • Macaca mulatta
  • Quinolines / pharmacology*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / enzymology
  • Simian Acquired Immunodeficiency Syndrome / pathology
  • Simian Immunodeficiency Virus / metabolism*


  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Quinolines
  • quinoline-val-asp(OMe)-CH2-OPH