Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo [see comments]

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo [see comments]

Nat Med. 2000 Jul;6(7):762-8. Unique Identifier : AIDSLINE MED/20348026
Chapuis AG; Paolo Rizzardi G; D'Agostino C; Attinger A; Knabenhans C; Fleury S; Acha-Orbea H; Pantaleo G; Laboratory of AIDS Immunopathogenesis, Department of Medicine,; Division of Infectious Diseases, Centre Hospitalier Universitaire; Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.

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.

Keywords: CLINICAL TRIAL JOURNAL ARTICLE Anti-HIV Agents/*THERAPEUTIC USE *Apoptosis CD4-Positive T-Lymphocytes/DRUG EFFECTS CD8-Positive T-Lymphocytes/DRUG EFFECTS Dose-Response Relationship, Drug Human HIV Infections/*DRUG THERAPY Immunosuppressive Agents/PHARMACOLOGY/THERAPEUTIC USE Lymphocyte Transformation/DRUG EFFECTS Mycophenolic Acid/*ANALOGS & DERIVATIVES/PHARMACOLOGY/ *THERAPEUTIC USE Support, Non-U.S. Gov't T-Lymphocytes/*DRUG EFFECTS
Comment in: Nat Med 2000 Jul;6(7):735-6
001030
A00A1115

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