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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Authors | A G Chapuis, G Paolo Rizzardi, C D'Agostino, A Attinger, C Knabenhans, S Fleury, H Acha-Orbea, G Pantaleo |
Journal | Nature medicine
(Nat Med)
Vol. 6
Issue 7
Pg. 762-8
(Jul 2000)
ISSN: 1078-8956 [Print] United States |
PMID | 10888924
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- Immunosuppressive Agents
- Mycophenolic Acid
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Topics |
- Anti-HIV Agents
(therapeutic use)
- Apoptosis
- CD4-Positive T-Lymphocytes
(drug effects)
- CD8-Positive T-Lymphocytes
(drug effects)
- Dose-Response Relationship, Drug
- HIV Infections
(drug therapy)
- Humans
- Immunosuppressive Agents
(pharmacology, therapeutic use)
- Lymphocyte Activation
(drug effects)
- Mycophenolic Acid
(analogs & derivatives, pharmacology, therapeutic use)
- T-Lymphocytes
(drug effects)
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