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Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo

Nature Medicine volume 6, pages 762–768 (2000)Cite this article

Abstract

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4+ and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.

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Figure 1: Effect of MPA on HIV infection in highly purified CD4+ T-cell populations.
Figure 2: Effect of MPA on the proliferation of activated T cells.
Figure 3: MPA induces apoptosis and cell death in activated T cells.
Figure 4: T-cell percent values and counts before and after addition of MMF to HAART.
Figure 5: Changes in the numbers and percents of dividing CD4 and CD8 T cells after therapy with MMF.
Figure 6: Effect of MMF therapy on virus isolation.

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Acknowledgements

This work was supported by Swiss National Foundation Grant number 3139-058913.99, and by unrestricted research grants of Hoffman La-Roche and GlaxoWellcome.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases, Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011, Lausanne, Switzerland

    Aude G. Chapuis, G. Paolo Rizzardi, Claudia D'Agostino, Christian Knabenhans, Sylvain Fleury & Giuseppe Pantaleo

  2. Division of Immunology and Allergy, Lausanne Branch and Institute of Biochemistry, University of Lausanne, 1066, Epalinges, Switzerland

    Hans Acha-Orbea & Giuseppe Pantaleo

  3. Ludwig Institute for Cancer Research, Lausanne Branch, and Institute of Biochemistry, University of Lausanne,, 1066, Epalinges, Switzerland

    Antoine Attinger

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Correspondence to Giuseppe Pantaleo.

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Chapuis, A., Paolo Rizzardi, G., D'Agostino, C. et al. Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo. Nat Med 6, 762–768 (2000). https://doi.org/10.1038/77489

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